InfluenzaPhase 2NCT01181323

Post-Partum Immunization With Live Attenuated Influenza Vaccine (LAIV) or Trivalent Influenza Vaccine (TIV) in Post-Partum Breast Feeding Women

A Phase 2 study testing Cold-adapted live attenuated influenza virus vaccine, trivalent and Trivalent inactivated influenza vaccine in people with Influenza, run by National Institute of Allergy and Infectious Diseases (NIAID) at 6 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 49 years, women onlyHealthy volunteers can take part
Conditions the study is for: Influenza
What is being tested?: Cold-adapted live attenuated influenza virus vaccine, trivalent and Trivalent inactivated influenza vaccine
Type of treatment: Vaccines, Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 240 participants
Where: 6 sitesUnited States
Study dates: Sep 2011to May 2013
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 49 years
Women only
Healthy volunteers accepted
Adult

Who may be able to join

Maternal Subject
Women age 18-49 years of age (inclusive) within 28-120 days of delivery.
Is in good health, as determined by vital signs (heart rate </=100 beats per minute (bpm); blood pressure: systolic <150 mm Hg; diastolic <90 mm Hg; oral temperature <100.0 degrees Fahrenheit), medical history and a targeted physical examination if indicated based on medical history.
Willing and capable of providing written informed consent for herself and infant.
Available for entire study duration, clinic visits and phone calls.
Planning on breast feeding from time of vaccination through 28 days post-vaccination. Breast milk must be at least one half of the source of the infant's feeding.

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Willing to practice adequate contraception for at least 28 days after receipt of study vaccine if not surgically sterile via post-partum tubal ligation, bilateral oophorectomy or hysterectomy. Adequate contraception may include, but is not limited to, abstinence, monogamous relationship with a vasectomized partner, barrier methods such as condoms or diaphragms with spermicides, or licensed hormonal methods that are compatible with breastfeeding an infant.
May be reached by any IRB-approved form of communication during study period. May include telephone, email, web based, social media, and/or text messaging, based on specific local IRB recommendations.
Agree to sign a medical release for herself and her infant (if needed) so that study personnel may obtain medical information about her or her infant's health.
Infant The infant(s) should be in good health as assessed by medical history, interview, rectal temperature and a targeted physical examination based on medical history.
Infant born greater than or equal to 36 weeks gestation.
Successful receipt of breast milk for at least two days prior to enrollment. Breast milk must be at least one half of the source of feeding, i.e., some supplementation is acceptable.

Who cannot join

Maternal Subject
History of receipt of licensed influenza vaccine for the current influenza season. (If enrolled in 2011-2012 season [October 2011 - February 2012], subject must not have received 2011-2012 influenza vaccine. If enrolled in the 2012-2013 season [July 2012 or later], subject must not have received 2012-2013 influenza vaccine).
History of previous participation in this study.
Known allergy to eggs, egg proteins or other components in the vaccines (i.e. formaldehyde, polyethylene glycol, p-isooctylphenyl ether, sucrose, gelatin, polysorbate 80, gentamicin, arginine, sodium phosphate, sodium chloride, octylphenol ethoxylate, EDTA).
If enrolled in the 2011-2012 season, known or suspected latex allergy. For the 2012-2013 season, known or suspected latex allergy is not a reason for exclusion.
History of severe reactions following immunization with contemporary influenza virus vaccines.

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Received any other licensed vaccines within 14 days (for inactivated vaccines) or 28 days (for live vaccines) prior to vaccination in this study, or expects to receive a licensed vaccine during the 28 days after vaccination in this study.
Received an experimental/investigational agent (vaccine, drug, biologic, device, blood product, or medication) within 28 days prior to vaccination in this study, or expects to receive an experimental/investigational agent within the study time period (180 days after vaccination in this study).
Received antiviral agent against influenza A and/or B within 48 hours prior to vaccination in this study. Antiviral agents should not be administered until 2 weeks after vaccination in this study unless medically necessary.
A moderate to severe acute illness and/or an oral temperature >/= 100.0 F, within 72 hr prior to vaccination. (This may result in a temporary delay of vaccination).
Immunosuppression as a result of an underlying illness or treatment, or use of anti-cancer chemotherapy or radiation therapy within the preceding 36 months.
Active neoplastic disease or a history of any hematologic malignancy (cancers of blood or bone marrow) or current bleeding or blood clotting disorder.
Current diagnosis of asthma.
History of asthma, wheezing, or bronchospasm in the last 5 years.
Long term (at least 14 days of prednisone 2 mg/kg or equivalent other glucocorticoid) use of oral or parenteral steroids, high-dose inhaled steroids (>800 microgram/day of beclomethasone dipropionate or equivalent) within the preceding 6 months (topical steroids are allowed).
Use of intranasal steroids within 14 days prior to vaccination in this study or within 14 days after receipt of study vaccine.
Use of intranasal products within 6 hours prior to vaccination in this study or expects to use intranasal products within 6 hours post study vaccination.
History of receiving immunoglobulin or other blood product (with exception of RhoGAM) within the 3 months prior to vaccination in this study.
Diagnosis of a current and uncontrolled major psychiatric disorder.
Has been hospitalized within the past 10 years for psychiatric illness, suicide attempt, or confinement for danger to self or others.
The subject is receiving listed psychiatric drugs (aripiprazole, clozapine, ziprasidone, haloperidol, molindone, loxapine, thioridazine, thiothixene, pimozide, fluphenazine, risperidone, mesoridazine, quetiapine, trifluoperazine, trifluopromazine, chlorprothixene, chlorpromazine, perphenazine, olanzapine, carbamazepine, divalproex sodium, lithium carbonate or lithium citrate). Subjects who are receiving a single antidepressant drug and are stable for at least 3 months prior to enrollment without decompensating are allowed enrollment into the study.
The subject is receiving medications contraindicated with breast feeding.
Known active human immunodeficiency virus (HIV), hepatitis B, or hepatitis C infection.
An active neurological (such as, but not limited to seizure disorder), auto-immune or vascular disease.
Active breast infection or breast abscess. (Study vaccination will be delayed until this breast infection or breast abscess has been treated and is resolved.)
History of frequent epistaxis (nose bleeds).
History of alcohol or drug abuse in the 1 year prior to enrollment.
History of Guillain-Barré syndrome.
Any known immunocompromised family member/household contact (such as active cancer, lupus, inflammatory bowel disease, HIV infection, or receipt of an organ or bone marrow transplant).
Has an acute or chronic medical condition that, in the opinion of the investigator would interfere with the evaluation of responses (this includes, but is not limited to: known chronic liver, lung or heart disease, chronic anemia, metabolic disorders such as diabetes (resolved gestational diabetes is acceptable), significant renal disease, transplant recipients).
Pregnant or planning to become pregnant during the 28 days after receipt of study vaccine.
Has any condition that would, in the opinion of the site investigator, place the subject at an unacceptable risk of injury or render the subject unable to meet the requirements of the protocol.
Infant
Major congenital malformations.
Syndromes that affect breastfeeding.
Progressive neurological disease or a history of any seizure.
Chronic lung disease or oxygen requirement for heart disease.
History of bronchopulmonary dysplasia, wheezing, reactive airway disease, hospitalization for respiratory illness, or use of bronchodilators.
Any receipt of glucocorticoids.
Immunodeficiency disease or use of immunosuppressive therapy including perinatal exposure to or infection with HIV, or known infection with hepatitis B or hepatitis C.
Received an experimental/investigational agent (vaccine, drug, biologic, device, blood product, or medication) within 28 days prior to this study, or expects to receive an experimental/investigational agent within the study time period (180 days after mother's vaccination in this study).
A moderate to severe acute illness and/or a rectal temperature greater than or equal to 100.0 F (37.8 C), within 72 hours prior to mother's vaccination (This may result in a temporary delay of vaccination in mother).
Received any licensed vaccines within 7 days prior to mother's vaccination in this study, or expects to receive a licensed vaccine during the 10 days after mother's vaccination in this study (This may result in a temporary delay of vaccination in mother).
History of documented laboratory-confirmed influenza infection.
Receipt of blood or blood products.
Have a condition that may place the infant at an unacceptable risk of injury or would make it difficult for the infant to meet the requirements of the study.

Trial locations and contacts

6 sites in 1 country.

City, postcode or hospital

6 sites in 1 country

United States6 sites

Emory Children's Center - Pediatric Infectious Diseases
Atlanta, Georgia, 30322-1014
Cincinnati Children's Hospital Medical Center - Infectious Diseases
Cincinnati, Ohio, 45229-3026
Duke Translational Medicine Institute - Clinical Vaccine Unit
Durham, North Carolina, 27704-2120
Group Health Research Institute - Seattle
Seattle, Washington, 98101-1466
Saint Louis University - Center for Vaccine Development
St Louis, Missouri, 63104-1015
Washington Hospital Center - Obstetrics and Gynecology
Washington D.C., District of Columbia, 20010-3017

Other trials in United States

About this study

Official title: A Randomized, Double-Blind Trial, Comparing the Safety in Mothers and Their Infants and Immunogenicity in Mothers of Live Attenuated Influenza Vaccine (LAIV) to Inactivated Trivalent Influenza Vaccine (TIV) When Administered to Breast Feeding Women

The purpose of this research study is to learn more about the safety of 2 licensed flu vaccines, nasal spray and flu vaccine shot, in mothers and their infants, when given to women who are breastfeeding and to compare the immune response (body's defense against foreign substances) of breastfeeding mothers, who receive intranasal flu vaccine, with breastfeeding mothers receiving the flu vaccine shot. Healthy women (240 volunteers, 28-120 days post delivery) who plan to breastfeed through 28 days post vaccination and who have not received influenza vaccine for the influenza season for which they are being enrolled, will be assigned by chance to 1 of the 2 vaccines in the following manner: flu vaccine nasal spray and a placebo (inactive substance) shot or a flu vaccine shot and a placebo nasal spray. Study procedures include: nasal swabs, blood samples, and completion of memory aids. Participants will be involved in this United States based study for about 6 months.

Read the detailed description

Due to limited data available on the safety and immune response to live attenuated influenza vaccine (LAIV) in breast-feeding women and the lack of information on the induction of immunoglobulin (Ig) A and IgG against influenza virus in breast milk, this study compares the safety in mothers and their infants and immunogenicity in mothers of standard dose inactivated trivalent influenza vaccine (TIV) and LAIV when administered between 28-120 days of delivery in breastfeeding women. This is a multi-site, randomized, double-blinded trial in 240 post-partum breastfeeding women, 18-49 years of age and their infants. Once enrolled, a blood sample and a breast milk sample will be collected. Nasal swabs will be obtained and targeted physical examinations (TPE) will be conducted from mother and infant, if indicated. Each subject will receive either a single intramuscular (IM) 0.5 milliliter (mL) dose of TIV and 0.2 mL of placebo administered intranasally, or 0.2 mL intranasal dose of LAIV and 0.5 mL of placebo administered IM. All subjects will maintain a memory aid recording oral temperature, and systemic and local adverse events (AEs) for 8 days after study products have been administered. Approximately day 2 and 8 all subjects will return to the clinic for collection of breast milk samples and nasal swabs (mother and infant) and the memory aid will be reviewed. Approximately Day 28 after vaccination, all subjects will return to the clinic for breast milk and a blood sampling. During the time between vaccination and the day 28 visit, if mother or infant has an influenza-like illness (ILI), a clinic visit may be required within 72 hours of illness onset. The clinic visit will be required for any illness that meets the Centers for Disease Control and Prevention's definition of an ILI for the mother. Investigator discretion will discern if an illness in the infant requires an ILI visit. Any respiratory or gastrointestinal (GI) serious adverse event (SAE) in the infant will also require a clinic visit. If the mother has an ILI, nasal swabs will be collected on her, and samples from the infant (if possible). If the infant has an ILI, nasal swabs will be collected on both the mother and infant. At approximately Day 42 after vaccination, all subjects will have a phone call for assessment of any medically attended GI or respiratory illness in the infant from Day 29-42. Approximately 6 months after vaccination all subjects will have a phone call for assessment of any SAEs in the subject or the infant since Day 42. SAE data and new onset chronic medical conditions in the mother will be collected from Day 0-180. At all study visits, subjects will be asked about acute, temporary breast diseases (mastitis, abscesses) and any changes in breastfeeding, i.e., interruption and if so, how long (in weeks). Subjects will report information on current breast milk consumption by infant. Unsolicited non-serious AE data will be captured Day 0-28. Respiratory and GI AEs will be captured for the infant from Day 28-42. SAE data will be captured from Day 0-180 for both mother and infant. Blood samples will be tested for hemagglutination inhibition (HAI), IgG, and IgA as measured by enzyme linked-immunosorbent assay (ELISA). Breast milk samples will be assayed for IgA and IgG antibodies by ELISA. Breast milk and nasal swabs will also be tested for LAIV. Parent protocol to sub-study 11-0048.

Conditions: Influenza
Being tested: Placebo, Cold-adapted live attenuated influenza virus vaccine, trivalent, Trivalent inactivated influenza vaccine
Keywords: influenza, vaccine, breastfeeding, post-partum women, infant, LAIV, TIV, parent protocol
Medical subject headings: Influenza, Human, Breast Feeding

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

PlaceboOther
0.2 ml of Intranasal placebo study product (using sucrose phosphate placebo filled sprayers), will be administered to maternal subjects.
Cold-adapted live attenuated influenza virus vaccine, trivalentBiological
Licensed product formulated for the 2011-2012 or 2012-2013 influenza season. Standard dose LAIV (Flumist®) 0.1 ml administered to maternal subjects intranasally in each nostril for a total of 0.2 mL.
PlaceboOther
0.5 ml of Sterile saline (0.9 percent Sodium Chloride for injection), administered IM to maternal subjects.
Trivalent inactivated influenza vaccineBiological
Preservative free, licensed product formulated for the 2011-2012 or 2012-2013 influenza season. Standard dose of TIV (Fluzone®) 0.5 ml administered to maternal subjects, IM in the deltoid.

Study groups in NCT01181323
Study group	Role	What they receive
Group 1: LAIV	Experimental	0.2 ml of Live attenuated influenza vaccine (LAIV), Flumist® given intranasally (IN) and 0.5 ml of placebo given intramuscularly (IM) injection administered to 120 maternal subjects. Receives: Biological: Cold-adapted live attenuated influenza virus vaccine, trivalent; Other: Placebo
Group 2: TIV	Experimental	0.5 ml of Inactivated Trivalent Influenza Vaccine (TIV), Fluzone® given intramuscularly (IM) and 0.2 ml of placebo given intranasally (IN) administered to 120 maternal subjects. Receives: Other: Placebo; Biological: Trivalent inactivated influenza vaccine

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of Participants Reporting Serious Adverse Events (SAEs)
Serious adverse events included any untoward medical occurrence that resulted in death; was life threatening; was a persistent/significant disability/incapacity; required inpatient hospitalization or prolongation thereof; was a congenital anomaly/birth defect; or may have jeopardized the participant, or required intervention to prevent one of the outcomes, regardless of relationship to study product or study participation.
Measured: Day 0 to Day 180 post vaccination
Number of Participants Reporting New Onset Chronic Medical Conditions
New onset chronic medical condition was defined as any new ICD-10 diagnosis for a participant that was expected to continue for at least 6 months and require continued health care intervention. ICD-10 = International Statistical Classification of Diseases and Related Health Problems, 10th revision. Maternal participants were asked at each visit through 180 days after enrollment if they or their infants had any new diagnosis.
Measured: Day 0 to Day 180 post vaccination
Number of Infant Participants Reporting Solicited Systemic Adverse Events Within 11 Days of Maternal Vaccination
Maternal participants maintained a memory aid to record daily the occurrence in their infants of systemic adverse events of fever (defined as rectal temperature 37.8 degrees Celsius or greater), drowsiness, irritability/fussiness, loss of appetite, nasal congestion, difficulty breathing, runny nose, and cough for 11 days (Day 0-10) after maternal vaccination based on protocol-defined grading (none, mild, moderate or severe) for each symptom. Rectal temperature was measured once daily. Participants are counted if they were reported as experiencing the symptom at any severity on any of the 11 days.
Measured: Day 0 to Day 10 post vaccination
Number of Participating Reporting Non-serious Unsolicited Adverse Events Related to Vaccination Within 28 Days of Maternal Vaccination
Adverse events (AE) for this protocol used the International Conference on Harmonization (ICH) guideline E6 definition of AE, any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product regardless of its causal relationship to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of investigational product. Related was defined as a reasonable possibility that the study product caused the AE. Reasonable possibility means that there is evidence to suggest a causal relationship between the study product and the adverse event. Non-serious AEs were those that did not meet the definition of serious (see Outcome Measure 1). Maternal participants were queried at each visit through 28 days after vaccination for the occurrence of any AE for her or the infant separately from the pre-defined solicited symptoms.
Measured: Day 0 to Day 28 post vaccination
Breast Milk ELISA IgA and IgG Geometric Mean Titers (GMT) to Each of the Vaccine Influenza Strains
Breast milk was collected at Day 0 prior to vaccination and again at 28 days following vaccination for testing in IgA and IgG ELISA Assays. The ELISA assay was conducted with the antigens in the 2011-2012 seasonal influenza vaccine, A/Perth/16/2009 (H3N2) and B/Brisbane/60/2008, those in the 2012-2013 seasonal influenza vaccine, A/Victoria/361/2011 and B/Wisconsin/1/2010, and the antigen in both seasons's vaccine, A/California/7/2009 (H1N1). The lower limit of detection is 5.82 units/mL for IgA and 2.56 units/mL for IgG. Titers below the limit of detection were reported as one-half the limit of detection.
Measured: Day 0 and 28 post vaccination
Number of Infant Participants With Medically Attended Respiratory or Gastrointestinal AEs 28-42 Days After Maternal Vaccination
Maternal participants were contacted by telephone at Day 42 to report all medically attended respiratory or gastrointestinal adverse events occurring in the infant participants between 28 and 42 days after maternal vaccination.
Measured: Within 28-42 days after maternal vaccination
Number of Maternal Participants Reporting Fever After Vaccination
Participants were provided with a thermometer and a memory aid on which to record daily oral temperatures for 8 days after vaccination (Day 0-7). The protocol defined fever as oral temperature of 37.8 degrees Celsius or higher. Participants are counted as experiencing fever if they reported oral temperatures of 37.8 degrees Celsius or higher on any of the 8 days.
Measured: Day 0-7 post vaccination
Number of Maternal Participants Reporting Solicited Subjective Systemic Symptoms After Vaccination
Participants maintained a memory aid to record daily the occurrence of systemic symptoms of feverishness, malaise, myalgia, headache, nausea, weakness, and chills for 8 days after vaccination (Day 0-7) based on their interference with daily activities. Participants are counted if they reported experiencing the symptom at any severity on any of the 8 days.
Measured: Day 0-7 post vaccination
Number of Maternal Participants Reporting Solicited Subjective Local Symptoms After Vaccination
Participants maintained a memory aid to record daily the occurrence of local symptoms of nasal congestion, runny nose, cough, sore throat, nasal bleeding, pain at injection site, tenderness at injection site, and swelling at injection site for 8 days after vaccination (Day 0-7) based on their interference with daily activities. Participants are counted if they reported experiencing the symptom at any severity on any of the 8 days.
Measured: Day 0-7 post vaccination
Number of Maternal Participants Reporting Solicited Quantitative Local Symptoms After Vaccination
Participants maintained a memory aid to record daily the occurrence of local reactions of redness and swelling for 8 days after vaccination (Day 0-7). If the reaction was present, the maximum diameter was measured in millimeters (mm). Participants are counted if they reported experiencing the reaction with any measurement greater than 0 mm on any of the 8 days.
Measured: Day 0-7 post vaccination

Secondary outcomes (12)

Geometric Mean Titers (GMT) in Maternal Sera of Hemagglutination Inhibition (HAI) Antibodies to Each of the Influenza Strains in the Vaccine Received
Blood was collected for HAI assay at Day 0 prior to vaccination and again at 28 days following vaccination. The HAI assay was conducted with the antigens in the 2011-2012 seasonal influenza vaccine, A/Perth/16/2009 (H3N2) and B/Brisbane/60/2008, those in the 2012-2013 seasonal influenza vaccine, A/Victoria/361/2011 and B/Wisconsin/1/2010, and the antigen in both seasons's vaccine, A/California/7/2009 (H1N1). The lower limit of detection for the assay was a titer of 10, sera samples below detection were given a value of 5 for analysis.
Measured: Day 0 and 28 post vaccination
Number of Maternal Participants With Season-specific LAIV Influenza A and B Strains Detected in Respiratory Secretions Prior to Vaccination.
Nasal swab samples were collected from all maternal participants prior to vaccination for PCR and cell culture to assess for the presence of the viruses in the LAIV vaccine in respiratory secretions. The data coordinating center selected 25% of participants in the TIV group for testing to serve as an internal control for the assay.
Measured: Day 0 prior to vaccination
Number of Maternal Participants With Season-specific LAIV Influenza A and B Strains Detected in Respiratory Secretions at Day 2 Post Vaccination.
Nasal swab samples were collected from all maternal participants at Day 2 post vaccination for PCR and cell culture to assess for the presence of the viruses in the LAIV vaccine in respiratory secretions. The data coordinating center selected 25% of participants in the TIV group for testing to serve as an internal control for the assay.
Measured: Day 2 post vaccination
Number of Maternal Participants With Season-specific LAIV Influenza A and B Strains Detected in Respiratory Secretions at Day 8 Post Vaccination.
Nasal swab samples were collected from all maternal participants at Day 8 post vaccination for PCR and cell culture to assess for the presence of the viruses in the LAIV vaccine in respiratory secretions. The data coordinating center selected 25% of participants in the TIV group for testing to serve as an internal control for the assay.
Measured: Day 8 post vaccination
Number of Infant Participants With Season-specific LAIV Influenza A and B Strains Detected in Respiratory Secretions Prior to Vaccination.
Nasal swab samples were collected from all infant participants prior to vaccination for PCR and cell culture to assess for the presence of the viruses in the LAIV vaccine in respiratory secretions. The data coordinating center selected 25% of participants in the TIV group for testing to serve as an internal control for the assay.
Measured: Day 0 prior to vaccination
Number of Infant Participants With Season-specific LAIV Influenza A and B Strains Detected in Respiratory Secretions at Day 2 Post Vaccination.
Nasal swab samples were collected from all infant participants at Day 2 post vaccination for PCR and cell culture to assess for the presence of the viruses in the LAIV vaccine in respiratory secretions. The data coordinating center selected 25% of participants in the TIV group for testing to serve as an internal control for the assay.
Measured: Day 2 post vaccination
Number of Infant Participants With Season-specific LAIV Influenza A and B Strains Detected in Respiratory Secretions at Day 8 Post Vaccination.
Nasal swab samples were collected from all infant participants at Day 8 post vaccination for PCR and cell culture to assess for the presence of the viruses in the LAIV vaccine in respiratory secretions. The data coordinating center selected 25% of participants in the TIV group for testing to serve as an internal control for the assay.
Measured: Day 8 post vaccination
Number of Maternal Participants Positive for the Season-specific LAIV Influenza A Strain in Respiratory Secretions at Day 0 Who Were Positive for H1N1 and/or H3N2 Strains.
Nasal swab samples were collected from all maternal participants prior to vaccination for PCR and cell culture to assess for the presence of the viruses in the LAIV vaccine in respiratory secretions. Those who were positive for the Influenza A strain were further tested to identify the H1N1 and H3N2 strain.
Measured: Day 0 prior to vaccination
Number of Maternal and Infant Participants Positive for the Season-specific LAIV Influenza A Strain in Respiratory Secretions at Day 2 Who Were Positive for H1N1 and/or H3N2 Strains.
Nasal swab samples were collected from all maternal and infant participants at Day 2 post vaccination for PCR and cell culture to assess for the presence of the viruses in the LAIV vaccine in respiratory secretions. Those who were positive for the Influenza A strain were further tested to identify the H1N1 and H3N2 strain.
Measured: Day 2 post vaccination
Number of Maternal Participants Positive for the Season-specific LAIV Influenza A Strain in Respiratory Secretions at Day 8 Who Were Positive for H1N1 and/or H3N2 Strains.
Nasal swab samples were collected from all maternal participants at Day 8 post vaccination for PCR and cell culture to assess for the presence of the viruses in the LAIV vaccine in respiratory secretions. Those who were positive for the Influenza A strain were further tested to identify the H1N1 and H3N2 strain.
Measured: Day 8 post vaccination
Number of Maternal Participants With Season-specific LAIV Influenza A and B Strains Detected in Breast Milk Following Vaccination.
Breast milk was collected from all maternal participants prior at Days 2 and 8 post vaccination for PCR and cell culture to assess for the presence of the viruses in the LAIV vaccine. The data coordinating center selected 25% of participants in the TIV group for testing to serve as an internal control for the assay.
Measured: Day 2 and 8 post vaccination
ELISA IgA and IgG GMT to Each of the Influenza Strains in the Vaccine Received in Sera of Maternal Subjects
Blood was collected from maternal subjects on Day 0 prior to vaccination, and at Day 28 post vaccination for assessment of IgA and IgG antibodies with a standard ELISA assay. The ELISA assay was conducted with the antigens in the 2011-2012 seasonal influenza vaccine, A/Perth/16/2009 (H3N2) and B/Brisbane/60/2008, those in the 2012-2013 seasonal influenza vaccine, A/Victoria/361/2011 and B/Wisconsin/1/2010, and the antigen in both seasons' vaccines, A/California/7/2009 (H1N1). The lower limit of detection is 5.82 units/mL for IgA and 2.56 units/mL for IgG. Titers below the limit of detection were reported as one-half the limit of detection.
Measured: Day 0 and Day 28 post vaccination

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Sep 2011May 2013

First posted13 Aug 2010 (estimated)
Study startSep 2011
Primary completionMay 2013
Study completionMay 2013

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for InfluenzaStudies of the same condition, open and under way.
More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind
Who is masked: Participant, Investigator, Outcomes assessor
Enrolment: 240 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01181323
Sponsor's protocol ID: 09-0007
Other IDs: HHSN272200800006C
Status last verified: Apr 2013
First submitted: 12 Aug 2010
Last updated: 28 Jan 2015
Results posted: Yes, on ClinicalTrials.gov

Publications

Brady RC, Jackson LA, Frey SE, Shane AL, Walter EB, Swamy GK, Schlaudecker EP, Szefer E, Wolff M, McNeal MM, Bernstein DI, Steinhoff MC. Randomized trial comparing the safety and antibody responses to live attenuated versus inactivated influenza vaccine when administered to breastfeeding women. Vaccine. 2018 Jul 25;36(31):4663-4671. doi: 10.1016/j.vaccine.2018.06.036. Epub 2018 Jun 28.
PubMed 29961606

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 28 Jan 2015. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomized, Double-Blind Trial, Comparing the Safety in Mothers and Their Infants and Immunogenicity in Mothers of Live Attenuated Influenza Vaccine (LAIV) to Inactivated Trivalent Influenza Vaccine (TIV) When Administered to Breast Feeding Women
ClinicalTrials.gov ID: NCT01181323
Acronym / sponsor ID: 09-0007
Conditions: Influenza
Keywords: influenza, vaccine, breastfeeding, post-partum women, infant, LAIV, TIV, parent protocol
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 240 participants (actual)
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
Study start: Sep 2011
Primary completion: May 2013 (actual)
Study completion: May 2013 (actual)
First posted: 13 Aug 2010 (estimated)
Results: Posted 16 May 2014

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
Group 1: LAIV	Experimental	Biological: Cold-adapted live attenuated influenza virus vaccine, trivalent, Other: Placebo0.2 ml of Live attenuated influenza vaccine (LAIV), Flumist® given intranasally (IN) and 0.5 ml of placebo given intramuscularly (IM) injection administered to 120 maternal subjects.
Group 2: TIV	Experimental	Other: Placebo, Biological: Trivalent inactivated influenza vaccine0.5 ml of Inactivated Trivalent Influenza Vaccine (TIV), Fluzone® given intramuscularly (IM) and 0.2 ml of placebo given intranasally (IN) administered to 120 maternal subjects.

Who may qualify

Ages: 18 to 49 years
Sex: Female only
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (12 listed)

Maternal Subject
Women age 18-49 years of age (inclusive) within 28-120 days of delivery.
Is in good health, as determined by vital signs (heart rate </=100 beats per minute (bpm); blood pressure: systolic <150 mm Hg; diastolic <90 mm Hg; oral temperature <100.0 degrees Fahrenheit), medical history and a targeted physical examination if indicated based on medical history.
Willing and capable of providing written informed consent for herself and infant.
Available for entire study duration, clinic visits and phone calls.

Key exclusion criteria (46 listed)

Maternal Subject
History of receipt of licensed influenza vaccine for the current influenza season. (If enrolled in 2011-2012 season [October 2011 - February 2012], subject must not have received 2011-2012 influenza vaccine. If enrolled in the 2012-2013 season [July 2012 or later], subject must not have received 2012-2013 influenza vaccine).
History of previous participation in this study.
Known allergy to eggs, egg proteins or other components in the vaccines (i.e. formaldehyde, polyethylene glycol, p-isooctylphenyl ether, sucrose, gelatin, polysorbate 80, gentamicin, arginine, sodium phosphate, sodium chloride, octylphenol ethoxylate, EDTA).
If enrolled in the 2011-2012 season, known or suspected latex allergy. For the 2012-2013 season, known or suspected latex allergy is not a reason for exclusion.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Placebo0.2 ml of Intranasal placebo study product (using sucrose phosphate placebo filled sprayers), will be administered to maternal subjects.	Other	Group 2: TIV
Cold-adapted live attenuated influenza virus vaccine, trivalentLicensed product formulated for the 2011-2012 or 2012-2013 influenza season. Standard dose LAIV (Flumist®) 0.1 ml administered to maternal subjects intranasally in each nostril for a total of 0.2 mL.	Biological	Group 1: LAIV
Placebo0.5 ml of Sterile saline (0.9 percent Sodium Chloride for injection), administered IM to maternal subjects.	Other	Group 1: LAIV
Trivalent inactivated influenza vaccinePreservative free, licensed product formulated for the 2011-2012 or 2012-2013 influenza season. Standard dose of TIV (Fluzone®) 0.5 ml administered to maternal subjects, IM in the deltoid.	Biological	Group 2: TIV

Primary outcome

Number of Participants Reporting Serious Adverse Events (SAEs)
Time frame: Day 0 to Day 180 post vaccination
Serious adverse events included any untoward medical occurrence that resulted in death; was life threatening; was a persistent/significant disability/incapacity; required inpatient hospitalization or prolongation thereof; was a congenital anomaly/birth defect; or may have jeopardized the participant, or required intervention to prevent one of the outcomes, regardless of relationship to study product or study participation.
Number of Participants Reporting New Onset Chronic Medical Conditions
Time frame: Day 0 to Day 180 post vaccination
New onset chronic medical condition was defined as any new ICD-10 diagnosis for a participant that was expected to continue for at least 6 months and require continued health care intervention. ICD-10 = International Statistical Classification of Diseases and Related Health Problems, 10th revision. Maternal participants were asked at each visit through 180 days after enrollment if they or their infants had any new diagnosis.
Number of Infant Participants Reporting Solicited Systemic Adverse Events Within 11 Days of Maternal Vaccination
Time frame: Day 0 to Day 10 post vaccination
Maternal participants maintained a memory aid to record daily the occurrence in their infants of systemic adverse events of fever (defined as rectal temperature 37.8 degrees Celsius or greater), drowsiness, irritability/fussiness, loss of appetite, nasal congestion, difficulty breathing, runny nose, and cough for 11 days (Day 0-10) after maternal vaccination based on protocol-defined grading (none, mild, moderate or severe) for each symptom. Rectal temperature was measured once daily. Participants are counted if they were reported as experiencing the symptom at any severity on any of the 11 days.
Number of Participating Reporting Non-serious Unsolicited Adverse Events Related to Vaccination Within 28 Days of Maternal Vaccination
Time frame: Day 0 to Day 28 post vaccination
Adverse events (AE) for this protocol used the International Conference on Harmonization (ICH) guideline E6 definition of AE, any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product regardless of its causal relationship to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of investigational product. Related was defined as a reasonable possibility that the study product caused the AE. Reasonable possibility means that there is evidence to suggest a causal relationship between the study product and the adverse event. Non-serious AEs were those that did not meet the definition of serious (see Outcome Measure 1). Maternal participants were queried at each visit through 28 days after vaccination for the occurrence of any AE for her or the infant separately from the pre-defined solicited symptoms.
Breast Milk ELISA IgA and IgG Geometric Mean Titers (GMT) to Each of the Vaccine Influenza Strains
Time frame: Day 0 and 28 post vaccination
Breast milk was collected at Day 0 prior to vaccination and again at 28 days following vaccination for testing in IgA and IgG ELISA Assays. The ELISA assay was conducted with the antigens in the 2011-2012 seasonal influenza vaccine, A/Perth/16/2009 (H3N2) and B/Brisbane/60/2008, those in the 2012-2013 seasonal influenza vaccine, A/Victoria/361/2011 and B/Wisconsin/1/2010, and the antigen in both seasons's vaccine, A/California/7/2009 (H1N1). The lower limit of detection is 5.82 units/mL for IgA and 2.56 units/mL for IgG. Titers below the limit of detection were reported as one-half the limit of detection.
Number of Infant Participants With Medically Attended Respiratory or Gastrointestinal AEs 28-42 Days After Maternal Vaccination
Time frame: Within 28-42 days after maternal vaccination
Maternal participants were contacted by telephone at Day 42 to report all medically attended respiratory or gastrointestinal adverse events occurring in the infant participants between 28 and 42 days after maternal vaccination.
Number of Maternal Participants Reporting Fever After Vaccination
Time frame: Day 0-7 post vaccination
Participants were provided with a thermometer and a memory aid on which to record daily oral temperatures for 8 days after vaccination (Day 0-7). The protocol defined fever as oral temperature of 37.8 degrees Celsius or higher. Participants are counted as experiencing fever if they reported oral temperatures of 37.8 degrees Celsius or higher on any of the 8 days.
Number of Maternal Participants Reporting Solicited Subjective Systemic Symptoms After Vaccination
Time frame: Day 0-7 post vaccination
Participants maintained a memory aid to record daily the occurrence of systemic symptoms of feverishness, malaise, myalgia, headache, nausea, weakness, and chills for 8 days after vaccination (Day 0-7) based on their interference with daily activities. Participants are counted if they reported experiencing the symptom at any severity on any of the 8 days.
Number of Maternal Participants Reporting Solicited Subjective Local Symptoms After Vaccination
Time frame: Day 0-7 post vaccination
Participants maintained a memory aid to record daily the occurrence of local symptoms of nasal congestion, runny nose, cough, sore throat, nasal bleeding, pain at injection site, tenderness at injection site, and swelling at injection site for 8 days after vaccination (Day 0-7) based on their interference with daily activities. Participants are counted if they reported experiencing the symptom at any severity on any of the 8 days.
Number of Maternal Participants Reporting Solicited Quantitative Local Symptoms After Vaccination
Time frame: Day 0-7 post vaccination
Participants maintained a memory aid to record daily the occurrence of local reactions of redness and swelling for 8 days after vaccination (Day 0-7). If the reaction was present, the maximum diameter was measured in millimeters (mm). Participants are counted if they reported experiencing the reaction with any measurement greater than 0 mm on any of the 8 days.

12 secondary outcomes

Geometric Mean Titers (GMT) in Maternal Sera of Hemagglutination Inhibition (HAI) Antibodies to Each of the Influenza Strains in the Vaccine Received
Time frame: Day 0 and 28 post vaccination
Number of Maternal Participants With Season-specific LAIV Influenza A and B Strains Detected in Respiratory Secretions Prior to Vaccination.
Time frame: Day 0 prior to vaccination
Number of Maternal Participants With Season-specific LAIV Influenza A and B Strains Detected in Respiratory Secretions at Day 2 Post Vaccination.
Time frame: Day 2 post vaccination
Number of Maternal Participants With Season-specific LAIV Influenza A and B Strains Detected in Respiratory Secretions at Day 8 Post Vaccination.
Time frame: Day 8 post vaccination
Number of Infant Participants With Season-specific LAIV Influenza A and B Strains Detected in Respiratory Secretions Prior to Vaccination.
Time frame: Day 0 prior to vaccination
Number of Infant Participants With Season-specific LAIV Influenza A and B Strains Detected in Respiratory Secretions at Day 2 Post Vaccination.
Time frame: Day 2 post vaccination
Number of Infant Participants With Season-specific LAIV Influenza A and B Strains Detected in Respiratory Secretions at Day 8 Post Vaccination.
Time frame: Day 8 post vaccination
Number of Maternal Participants Positive for the Season-specific LAIV Influenza A Strain in Respiratory Secretions at Day 0 Who Were Positive for H1N1 and/or H3N2 Strains.
Time frame: Day 0 prior to vaccination
Number of Maternal and Infant Participants Positive for the Season-specific LAIV Influenza A Strain in Respiratory Secretions at Day 2 Who Were Positive for H1N1 and/or H3N2 Strains.
Time frame: Day 2 post vaccination
Number of Maternal Participants Positive for the Season-specific LAIV Influenza A Strain in Respiratory Secretions at Day 8 Who Were Positive for H1N1 and/or H3N2 Strains.
Time frame: Day 8 post vaccination
Number of Maternal Participants With Season-specific LAIV Influenza A and B Strains Detected in Breast Milk Following Vaccination.
Time frame: Day 2 and 8 post vaccination
ELISA IgA and IgG GMT to Each of the Influenza Strains in the Vaccine Received in Sera of Maternal Subjects
Time frame: Day 0 and Day 28 post vaccination

Results and safety

Results posted to the registry on 16 May 2014, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Maternal LAIV	124	123
Maternal TIV	124	121
Infant LAIV	124	123
Infant TIV	125	122

Primary outcome: Number of Participants Reporting Serious Adverse Events (SAEs)

Time frame: Day 0 to Day 180 post vaccination. Number. Unit: participants

Measure	Maternal LAIV n = 124	Maternal TIV n = 124	Infant LAIV n = 124	Infant TIV n = 125
Value	1	0	2	1

Population analysed: All enrolled participants are included in the analysis population for this outcome measure.

Primary outcome: Number of Participants Reporting New Onset Chronic Medical Conditions

Time frame: Day 0 to Day 180 post vaccination. Number. Unit: participants

Measure	Maternal LAIV n = 124	Maternal TIV n = 124	Infant LAIV n = 124	Infant TIV n = 125
Value	1	1	3	4

Population analysed: All enrolled participants are included in the analysis population for this outcome measure.

Primary outcome: Number of Infant Participants Reporting Solicited Systemic Adverse Events Within 11 Days of Maternal Vaccination

Time frame: Day 0 to Day 10 post vaccination. Number. Unit: participants

Measure	Infant LAIV n = 124	Infant TIV n = 125
Fever	28	23
Drowsiness	42	33
Irritability/fussiness	74	56
Loss of appetite	20	14
Nasal congestion	54	54
Difficulty breathing	12	7
Runny nose	18	30
Cough	15	18

Primary outcome: Number of Participating Reporting Non-serious Unsolicited Adverse Events Related to Vaccination Within 28 Days of Maternal Vaccination

Time frame: Day 0 to Day 28 post vaccination. Number. Unit: participants

Measure	Maternal LAIV n = 124	Maternal TIV n = 124	Infant LAIV n = 124	Infant TIV n = 125
Value	6	3	5	8

Population analysed: All enrolled participants are included in the analysis population for this outcome measure

12 secondary outcomes are reported in the full results.

Adverse events

Time frame: Solicited systemic and local symptoms were collected for 8 days after vaccination (maternal), 10 days (infant). Unsolicited AEs were collected for 28 days and SAEs and new onset chronic medical conditions were collected for 6 months after vaccination.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Maternal LAIV	1 of 124 (0.8%)	106 of 124 (85.5%)	Not reported
Maternal TIV	0 of 124 (0%)	122 of 124 (98.4%)	Not reported
Infant LAIV	2 of 124 (1.6%)	102 of 124 (82.3%)	Not reported
Infant TIV	1 of 125 (0.8%)	101 of 125 (80.8%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 28 Jan 2015.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 29961606Brady RC, Jackson LA, Frey SE, Shane AL, Walter EB, Swamy GK, Schlaudecker EP, Szefer E, Wolff M, McNeal MM, Bernstein DI, Steinhoff MC. Randomized trial comparing the safety and antibody responses to live attenuated versus inactivated influenza vaccine when administered to breastfeeding women. Vaccine. 2018 Jul 25;36(31):4663-4671. doi: 10.1016/j.vaccine.2018.06.036. Epub 2018 Jun 28.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

6 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 46 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Jan 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 16 May 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants Reporting Serious Adverse Events (SAEs) (time frame: Day 0 to Day 180 post vaccination). The study lists 10 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01181323, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jan 2015.