DiphtheriaNCT02757950

A Post-marketing, Observational, Retrospective Study to Assess the Safety of RefortrixTM (Tdap) When Administered During Pregnancy in a Maternal Immunization Program in Brazil.

An observational study of Diphtheria, run by GlaxoSmithKline at 1 site in Brazil.

Completed

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

Trial summary

The purpose of this study is to assess the safety of RefortrixTM (Tdap) when administered during pregnancy in a maternal immunization program in Brazil. Read more about this study

Who is it for?: Ages 18 to 45 years, women only
Conditions the study is for: Diphtheria
What is being tested?: Combined diphtheria, tetanus and tricomponent acellular pertussis vaccine [Refortrix (Tdap)]
Type of treatment: Vaccines
How many people: 2,462 participants
Where: 1 siteBrazil
Study dates: 14 Jul 2016to 31 May 2017
Phase: Observational
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 45 years
Women only
No healthy volunteers
Adult

Study population: The subjects who delivered in the study centre from May 2015 onwards will be considered as potentially exposed and those who delivered before September 2014 will be considered as potentially unexposed

Who may be able to join

Subjects between 18 and 45 years of age at the time of pregnancy under consideration for the study, who deliver in the study centre.
Residents of the study area
Subjects who were compliant with the routine antenatal care including at least one ultrasound assessment report early in the pregnancy.
Subjects with the complete and relevant medical records available.
Subjects who received one dose of Refortrix vaccine in the recommended time period between 27 and 36 completed weeks of pregnancy (or as late as 20 days before delivery due date) as part of the maternal immunization program in Brazil, and according to the program recommendations from May 2015 onwards.
Subjects with appropriate vaccination records.
Subjects who had delivered in the same hospital (study centre) before 01 September 2014 (September 2012-August 2014) and who did not receive Tdap vaccination during pregnancy to the best knowledge of the investigator.

Who cannot join

Subjects who have been transferred to other specialised centres, where their medical records would be inaccessible for the study (private clinics, psychiatric or prison hospitals, other state hospitals, etc).

Trial locations and contacts

1 site in 1 country.

Brazil1 site

GSK Investigational Site
Santo André, São Paulo, 09060-650

Other trials in Brazil

About this study

Official title: A Post-marketing, Observational, Retrospective, Cohort Study to Assess the Safety of RefortrixTM (Tdap) When Administered During Pregnancy in a Maternal Immunization Program in Brazil.

The purpose of this study is to assess the safety of RefortrixTM (Tdap) when administered during pregnancy in a maternal immunization program in Brazil.

Read the detailed description

In this retrospective cohort study the safety of RefortrixTM (Tdap) administered during pregnancy as part of the National immunization program in Brazil will be assessed by comparing the risk of pre-defined adverse events before and after introduction of the RefortrixTM (Tdap) maternal immunization program.

Conditions: Diphtheria
Being tested: Combined diphtheria, tetanus and tricomponent acellular pertussis vaccine [Refortrix (Tdap)]
Keywords: exposed and unexposed cohorts, post-marketing, maternal immunization, neonate related Adverse Events, Congenital anomaly, RefortrixTM, Pregnancy related Adverse Events
Medical subject headings: Diphtheria, Congenital Abnormalities

What participants receive

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

Combined diphtheria, tetanus and tricomponent acellular pertussis vaccine [Refortrix (Tdap)]Biological
Subjects were included in the Exposed cohort if they received Refortrix as part of the maternal immunization program in Brazil.

Study groups in NCT02757950
Study group	Role	What they receive
Exposed cohort		Women, 18-45 years of age at the time of pregnancy, who delivered in the hospital (study centre) from May 2015 and who received one dose of Refortrix during 27 to 36 weeks of pregnancy (or as late as 20 days before delivery due date). Receives: Biological: Combined diphtheria, tetanus and tricomponent acellular pertussis vaccine [Refortrix (Tdap)]
Unexposed cohort		Women, 18-45 years of age at the time of pregnancy, who delivered in the hospital (study centre) before implementation of the maternal immunization program in Brazil in September 2014 and who did not receive Tdap vaccination during pregnancy. Receives: Biological: Combined diphtheria, tetanus and tricomponent acellular pertussis vaccine [Refortrix (Tdap)]

What is being measured

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

Number of Subjects Reporting Gestational Diabetes
Gestational diabetes was defined as: Onset or first recognition of abnormal glucose tolerance during pregnancy (the diagnosis is based on administration of glucose challenge test at 24-28 weeks of gestation). Includes Class A1: Euglycaemia achieved with diet and/or exercise and Class A2: Euglycaemia achieved with medication.
Measured: After week 27 of pregnancy
Number of Subjects Reporting Pregnancy-related Hypertension, Pre-eclampsia, Eclampsia, and HELLP Syndrome
Pregnancy-related hypertension is defined as:
Blood pressure systolic higher than (>) 140 and/or diastolic > 90 millimetre of mercury (mmHg), documented in at least two separate measurements after 20 weeks of gestation, without proteinuria or other stigmata of pre-eclampsia, and returning to normal post-partum. Hypertension usually resolves by 12 weeks post-partum, included pre-eclampsia, eclampsia and haemolysis elevated liver enzymes low platelet (HELLP) Syndrome for this study.
Measured: After week 27 of pregnancy
Number of Subjects Reporting Pregnancy Hemorrhage
Pregnancy vaginal hemorrhage is defined as: excessive blood loss after delivery i.e. estimated blood loss in excess of 500 milliliters (ml) after vaginal delivery and estimated blood loss in excess of 1000 ml after Caesarean delivery. The other symptoms are higher than or equal to (≥) 10 percent (%) drop in hematocrit, need for blood transfusion, symptomatic hypotension, dizziness, pallor and oliguria.
Vaginal or intrauterine hemorrhage that encompasses antepartum (i.e. bleeding from the genital tract after 24 weeks of gestation), intrapartum, and postpartum bleeding (i.e. within 24 hours post-delivery).
A major obstetric hemorrhage is defined as blood loss from uterus or genital tract >1500 ml or a decrease.
Measured: After week 27 of pregnancy
Number of Subjects With Pre-specified Neonate-related Outcomes Resulting in Preterm Birth
Preterm birth is defined as: Birth before 37 weeks of gestation.
Measured: From week 27 up to week 37 of pregnancy
Number of Subjects With Pre-specified Neonate-related Outcomes, Resulting in Neonates Small for Their Gestational Age
Small for gestational age is defined as: Birth weight less than (<) 10% for infants of same gestational age and gender in same population.
Measured: After week 27 of pregnancy

Secondary outcomes (3)

Number of Subjects Reporting Pregnancy-related Adverse Events (AEs) of Interest/Neonate-related Events up to Delivery
Pregnancy-related AEs of interest and neonate-related events are defined as: premature rupture of membranes, preterm premature rupture of membranes, premature uterine contraction, neonatal death, maternal death, still birth, neonatal hypoxic ischaemic encephalopathy.
Measured: After week 27 of pregnancy
Number of Subjects Reporting Cases of Congenital Anomalies in the Neonates
Congenital anomalies include morphological, functional, chromosomal or genetic anomalies, regardless of whether detected at birth or not, the foetus is delivered dead or alive, or defects are identified by prenatal ultrasound, amniocentesis or examination of the products of conception.
Measured: From week 27 of pregnancy up to birth
Number of Subjects With Pregnancy-related AEs and Birth Outcomes Per Calendar Year
Pregnancy related AEs include: gestational diabetes, pregnancy-related hypertension, pre-eclampsia, eclampsia, HELLP Syndrome and pregnancy hemorrhage. Birth outcomes include: preterm birth and small for gestational age.
Measured: After week 27 of pregnancy

Timeline

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

14 Jul 201631 May 2017

First posted2 May 2016 (estimated)
Study start14 Jul 2016
Primary completion31 May 2017
Study completion31 May 2017

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 DiphtheriaStudies of the same condition, open and under way.
More trials run by GlaxoSmithKlineThe 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: Observational
Observational model: Cohort
Time perspective: Prospective
Enrolment: 2,462 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02757950
Sponsor's protocol ID: 203153
Status last verified: Sep 2019
First submitted: 28 Apr 2016
Last updated: 1 Oct 2019
Results posted: Yes, on ClinicalTrials.gov
Individual data sharing: No

Publications

Sancovski M, Mesaros N, Feng Y, Ceregido MA, Luyts D, De Barros E. Safety of reduced antigen content diphtheria-tetanus-acellular pertussis vaccine when administered during pregnancy as part of the maternal immunization program in Brazil: a single center, observational, retrospective, cohort study. Hum Vaccin Immunother. 2019;15(12):2873-2881. doi: 10.1080/21645515.2019.1627161. Epub 2019 Jun 20.
PubMed 31216218

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?

See locations

RecruitingPhase 2
A Phase II Clinical Trial of Absorbed Acellular Pertussis (Two-Component) Diphtheria-Tetanus Combined Vaccine (For Adults and Adolescents)
Pertussis (Whooping Cough), Diphtheria
RecruitingPhase 1/2
A Phase I/II Clinical Trial of the Diphtheria, Tetanus, Acellular Component Pertussis and Sabin Inactivated Poliomyelitis Vaccine Adsorbed
Diphtheria, Pertussis
RecruitingPhase 4
Concurrent Versus Sequential Administration of Tdap and RSV Vaccines in Pregnancy
RSV, Tdap - Tetanus, Diphtheria and Acellular Pertussis Vaccination
Not yet recruitingPhase 1/2
Safety and Immunogenicity of a Combined Diphtheria, Tetanus, Whole Cell Pertussis, Hepatitis B, Recombinant Poliomyelitis and Haemophilus Influenzae Type b (Hib) Vaccine (SIIPL DTwP-HepB-rPV-Hib)
Diptheria Immunization, Tetanus Immunization
Active, not recruitingPhase 3
A Study on the Immune Response and Safety of a Combined Vaccine Against Diphtheria, Tetanus and Acellular Pertussis (dTpa) in Japanese Healthy Pregnant Women
Diphtheria-Tetanus-acellular Pertussis Vaccines

All Diphtheria trials

Study at a glance

From the registry record, last updated by the sponsor on 1 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Post-marketing, Observational, Retrospective, Cohort Study to Assess the Safety of RefortrixTM (Tdap) When Administered During Pregnancy in a Maternal Immunization Program in Brazil.
ClinicalTrials.gov ID: NCT02757950
Acronym / sponsor ID: 203153
Conditions: Diphtheria
Keywords: exposed and unexposed cohorts, post-marketing, maternal immunization, neonate related Adverse Events, Congenital anomaly, RefortrixTM, Pregnancy related Adverse Events
Study type: Observational
Recruitment status: Completed
Enrolment: 2,462 participants (actual)
Lead sponsor: GlaxoSmithKlineIndustry (pharma, biotech, devices)
Study start: 14 Jul 2016 (actual)
Primary completion: 31 May 2017 (actual)
Study completion: 31 May 2017 (actual)
First posted: 2 May 2016 (estimated)
Results: Posted 1 Oct 2019

Clinical summary

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

The purpose of this study is to assess the safety of RefortrixTM (Tdap) when administered during pregnancy in a maternal immunization program in Brazil.

Detailed description

Study design

Observational model: Cohort
Time perspective: Prospective
Number of arms: 2

Arm	Type	Receives
Exposed cohort	–	Biological: Combined diphtheria, tetanus and tricomponent acellular pertussis vaccine [Refortrix (Tdap)]Women, 18-45 years of age at the time of pregnancy, who delivered in the hospital (study centre) from May 2015 and who received one dose of Refortrix during 27 to 36 weeks of pregnancy (or as late as 20 days before delivery due date).
Unexposed cohort	–	Biological: Combined diphtheria, tetanus and tricomponent acellular pertussis vaccine [Refortrix (Tdap)]Women, 18-45 years of age at the time of pregnancy, who delivered in the hospital (study centre) before implementation of the maternal immunization program in Brazil in September 2014 and who did not receive Tdap vaccination during pregnancy.

Who may qualify

Ages: 18 to 45 years
Sex: Female only
Healthy volunteers: Not accepted
Age groups: Adult
Study population: The subjects who delivered in the study centre from May 2015 onwards will be considered as potentially exposed and those who delivered before September 2014 will be considered as potentially unexposed

Key inclusion criteria (7 listed)

Subjects between 18 and 45 years of age at the time of pregnancy under consideration for the study, who deliver in the study centre.
Residents of the study area
Subjects who were compliant with the routine antenatal care including at least one ultrasound assessment report early in the pregnancy.
Subjects with the complete and relevant medical records available.
Subjects who received one dose of Refortrix vaccine in the recommended time period between 27 and 36 completed weeks of pregnancy (or as late as 20 days before delivery due date) as part of the maternal immunization program in Brazil, and according to the program recommendations from May 2015 onwards.

Key exclusion criteria (1 listed)

Subjects who have been transferred to other specialised centres, where their medical records would be inaccessible for the study (private clinics, psychiatric or prison hospitals, other state hospitals, etc).

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
Combined diphtheria, tetanus and tricomponent acellular pertussis vaccine [Refortrix (Tdap)]Subjects were included in the Exposed cohort if they received Refortrix as part of the maternal immunization program in Brazil.	Biological	Exposed cohort, Unexposed cohort

Primary outcome

Number of Subjects Reporting Gestational Diabetes
Time frame: After week 27 of pregnancy
Gestational diabetes was defined as: Onset or first recognition of abnormal glucose tolerance during pregnancy (the diagnosis is based on administration of glucose challenge test at 24-28 weeks of gestation). Includes Class A1: Euglycaemia achieved with diet and/or exercise and Class A2: Euglycaemia achieved with medication.
Number of Subjects Reporting Pregnancy-related Hypertension, Pre-eclampsia, Eclampsia, and HELLP Syndrome
Time frame: After week 27 of pregnancy
Pregnancy-related hypertension is defined as: Blood pressure systolic higher than (>) 140 and/or diastolic > 90 millimetre of mercury (mmHg), documented in at least two separate measurements after 20 weeks of gestation, without proteinuria or other stigmata of pre-eclampsia, and returning to normal post-partum. Hypertension usually resolves by 12 weeks post-partum, included pre-eclampsia, eclampsia and haemolysis elevated liver enzymes low platelet (HELLP) Syndrome for this study.
Number of Subjects Reporting Pregnancy Hemorrhage
Time frame: After week 27 of pregnancy
Pregnancy vaginal hemorrhage is defined as: excessive blood loss after delivery i.e. estimated blood loss in excess of 500 milliliters (ml) after vaginal delivery and estimated blood loss in excess of 1000 ml after Caesarean delivery. The other symptoms are higher than or equal to (≥) 10 percent (%) drop in hematocrit, need for blood transfusion, symptomatic hypotension, dizziness, pallor and oliguria. Vaginal or intrauterine hemorrhage that encompasses antepartum (i.e. bleeding from the genital tract after 24 weeks of gestation), intrapartum, and postpartum bleeding (i.e. within 24 hours post-delivery). A major obstetric hemorrhage is defined as blood loss from uterus or genital tract >1500 ml or a decrease.
Number of Subjects With Pre-specified Neonate-related Outcomes Resulting in Preterm Birth
Time frame: From week 27 up to week 37 of pregnancy
Preterm birth is defined as: Birth before 37 weeks of gestation.
Number of Subjects With Pre-specified Neonate-related Outcomes, Resulting in Neonates Small for Their Gestational Age
Time frame: After week 27 of pregnancy
Small for gestational age is defined as: Birth weight less than (<) 10% for infants of same gestational age and gender in same population.

3 secondary outcomes

Number of Subjects Reporting Pregnancy-related Adverse Events (AEs) of Interest/Neonate-related Events up to Delivery
Time frame: After week 27 of pregnancy
Number of Subjects Reporting Cases of Congenital Anomalies in the Neonates
Time frame: From week 27 of pregnancy up to birth
Number of Subjects With Pregnancy-related AEs and Birth Outcomes Per Calendar Year
Time frame: After week 27 of pregnancy

Results and safety

Results posted to the registry on 1 Oct 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Exposed Cohort	1,203	1,199
Unexposed Cohort	1,259	1,248

Primary outcome: Number of Subjects Reporting Gestational Diabetes

Time frame: After week 27 of pregnancy. Count of participants. Unit: Participants

Measure	Exposed Cohort n = 1199	Unexposed Cohort n = 1259
Value	10	22

Exposed Cohort vs Unexposed Cohort: Incidence rate ratio: 0.548 (95% CI 0.259 to 1.157), p = 0.1147, Regression, Logistic

Population analysed: Analysis was performed on the Total Cohort (TC), which included all the subjects enrolled in the study with symptom sheets filled-in.

Primary outcome: Number of Subjects Reporting Pregnancy-related Hypertension, Pre-eclampsia, Eclampsia, and HELLP Syndrome

Time frame: After week 27 of pregnancy. Count of participants. Unit: Participants

Measure	Exposed Cohort n = 1199	Unexposed Cohort n = 1259
Pregnancy-related hypertension	11	31
Pre-eclampsia	10	30
Eclampsia	2	0
HELLP syndrome	0	1

Exposed Cohort vs Unexposed Cohort: Incidence rate ratio: 0.428 (95% CI 0.215 to 0.851), p = 0.0155, Regression, Logistic

Population analysed: Analysis was performed on the Total Cohort (TC), which included all the subjects enrolled in the study with symptom sheets filled-in.

Primary outcome: Number of Subjects Reporting Pregnancy Hemorrhage

Time frame: After week 27 of pregnancy. Count of participants. Unit: Participants

Measure	Exposed Cohort n = 1199	Unexposed Cohort n = 1259
Value	4	19

Exposed Cohort vs Unexposed Cohort: Incidence rate ratio: 0.254 (95% CI 0.086 to 0.746), p = 0.0127, Regression, Logistic

Population analysed: Analysis was performed on the Total Cohort (TC), which included all the subjects enrolled in the study with symptom sheets filled-in.

Primary outcome: Number of Subjects With Pre-specified Neonate-related Outcomes Resulting in Preterm Birth

Time frame: From week 27 up to week 37 of pregnancy. Count of participants. Unit: Participants

Measure	Exposed Cohort n = 1199	Unexposed Cohort n = 1259
Value	64	121

Exposed Cohort vs Unexposed Cohort: Incidence rate ratio: 0.638 (95% CI 0.471 to 0.863), p = 0.0036, Regression, Logistic

Population analysed: Analysis was performed on the Total Cohort (TC), which included all the subjects enrolled in the study with symptom sheets filled-in.

3 secondary outcomes are reported in the full results.

Adverse events

Time frame: Entire study period (From week 27 of pregnancy up to birth).. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Unexposed Cohort	0 of 0	0 of 0	0
Exposed Cohort	0 of 0	0 of 0	0

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 1 Oct 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 31216218Sancovski M, Mesaros N, Feng Y, Ceregido MA, Luyts D, De Barros E. Safety of reduced antigen content diphtheria-tetanus-acellular pertussis vaccine when administered during pregnancy as part of the maternal immunization program in Brazil: a single center, observational, retrospective, cohort study. Hum Vaccin Immunother. 2019;15(12):2873-2881. doi: 10.1080/21645515.2019.1627161. Epub 2019 Jun 20.
Individual participant dataSharing planned: No

Related trials for Diphtheria

RecruitingPhase 2
A Phase II Clinical Trial of Absorbed Acellular Pertussis (Two-Component) Diphtheria-Tetanus Combined Vaccine (For Adults and Adolescents)
Pertussis (Whooping Cough), Diphtheria
RecruitingPhase 1/2
A Phase I/II Clinical Trial of the Diphtheria, Tetanus, Acellular Component Pertussis and Sabin Inactivated Poliomyelitis Vaccine Adsorbed
Diphtheria, Pertussis
RecruitingPhase 4
Concurrent Versus Sequential Administration of Tdap and RSV Vaccines in Pregnancy
RSV, Tdap - Tetanus, Diphtheria and Acellular Pertussis Vaccination
Not yet recruitingPhase 1/2
Safety and Immunogenicity of a Combined Diphtheria, Tetanus, Whole Cell Pertussis, Hepatitis B, Recombinant Poliomyelitis and Haemophilus Influenzae Type b (Hib) Vaccine (SIIPL DTwP-HepB-rPV-Hib)
Diptheria Immunization, Tetanus Immunization
Active, not recruitingPhase 3
A Study on the Immune Response and Safety of a Combined Vaccine Against Diphtheria, Tetanus and Acellular Pertussis (dTpa) in Japanese Healthy Pregnant Women
Diphtheria-Tetanus-acellular Pertussis Vaccines

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.

GSK Clinical Trials study director

GlaxoSmithKline

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

Questions about this trial

What is this clinical trial studying?

An observational study of Diphtheria, run by GlaxoSmithKline at 1 site in Brazil.

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 7 inclusion and 1 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 1 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Brazil. 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.

Are results available for this study?

Yes. Results are posted in the registry (first posted 1 Oct 2019). 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 Subjects Reporting Gestational Diabetes (time frame: After week 27 of pregnancy). The study lists 5 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 NCT02757950, 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 1 Oct 2019.