Influenza, HumanPhase 4NCT01967368
Safety and Efficacy of Intradermal Trivalent Influenza Vaccination in Institutionalized Older Adults
A Phase 4 study testing Intanza and Vaxigrip in people with Influenza, Human, run by The University of Hong Kong at 1 site in China.
Trial summary
Influenza is associated with significant morbidity and mortality. Institutionalized older adults (age>65) is the group associated with highest risk of complications. Influenza vaccines are the cornerstone of influenza prevention but one systematic review has found that there is no statistically significant difference… Read more about this study
- Who is it for?
- Ages 65 years and olderHealthy volunteers can take part
- Conditions the study is for
- Influenza, Human
- What is being tested?
- Intanza and Vaxigrip
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 1 siteChina
- Study dates
- Oct 2013to Jun 2015
- Phase
- Phase 4
- Are there results?
- None posted in the registry
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 65 years and older
- All sexes
- Healthy volunteers accepted
- Older adult
Who may be able to join
- Institutionalized older adult patients at the age of 65 or above
Who cannot join
- Clinically significant immune-related diseases and significant recent co-morbidities
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Queen Mary Hospital and Fung Yiu King Hospital, Hong Kong West Cluster, Hospital Authority
Hong Kong
Tuen Ching Chan, MBBS, 85266816077, tuenching@yahoo.com.hk
Tuen Ching Chan, MBBS
About this study
Influenza is associated with significant morbidity and mortality. Institutionalized older adults (age>65) is the group associated with highest risk of complications. Influenza vaccines are the cornerstone of influenza prevention but one systematic review has found that there is no statistically significant difference against laboratory confirmed influenza. A major reason is immune senescence in older adults which result in weaker response towards vaccines when compared with young adults. Intradermal administration of vaccine has been suggested to improve immune response due to the abundance of immunostimulatory cells, such as dendritic cells in the dermis. Intradermal administration of influenza vaccine has been shown to have comparable or superior efficacy compared with intramuscular administration in the >60-year old population and the rates of adverse events post-vaccination were also comparable between them. The immunogenicity of intradermal administration has also been shown to be better in immunocompromised patients, including community dwelling older adults. In addition, intradermal vaccination has good acceptability and safety profile in different countries, so it has been licensed in Hong Kong and worldwide. However, there is little study regarding the efficacy of intradermal vaccination of influenza in institutionalized older adults, investigators therefore would like to perform a prospective, randomized study to compare the safety and immunogenicity between conventional full dose intramuscular immunization and full dose intradermal immunization of the trivalent influenza vaccine in institutionalized older adults.
The hypothesis is that full dose intradermal trivalent influenza vaccination is as effective as full-dose standard intramuscular injection in terms of seroconversion and seroprotection rate in institutionalized older adults. Finding of this study will be important in the vaccination of institutionalized older adults and immunocompromised patients as intradermal vaccine may induce a better immune response against influenza infection.
Read the detailed description
This is a prospective, randomized, parallel-group single centre trial in the Queen Mary Hospital and Fung Yiu King Hospital. Investigators aim to recruit 100 subjects who would be qualified for the Hospital Authority (HA)/ Centre for Health Protection (CHP) Mass Vaccination Program for Trivalent influenza vaccine (TIV). These patients include Institutionalized older adult patients at the age of 65 or above.
After informed consent (allow patient one week to consider) subjects will be randomly assigned into 2 groups to receive the following vaccines: Group 1: the full-dose (1 dose) standard TIV (15ug hemagglutinin TIV) delivered intramuscularly using a conventional needle, Group 2: a full-dose (1 dose) intradermal injection (15ug hemagglutinin TIV) delivered with the Intanza 15 at day 0. All TIV vaccines used in this study will be either of Vaxigrip® (Group 1) or Intanza® Intradermal (Group 2), Sanofi-Pasteur and provided by the Hospital Authority or the University of Hong Kong. Baseline HI to the TIV will be measured at day 0.
Patients fulfilling the inclusion criteria will be screened from the Community Geriatric Assessment Team (CGAT) of Fung Yiu King Hospital by the investigators. Before commencing, patients would be allowed to have one week to consider joining the study. Meanwhile, investigators would also take 5ml of serum from the participant to test for the baseline TIV antibody. Principal Investigator is experienced in administering intramuscular injections and he would be responsible for refilling the low-dose intradermal injection in a sterile technique. The microneedle device used in this study comprises an array of three 0.6 mm microneedles, made up of silicon crystal, and bonded to the tip of a plastic adapter, which can be mounted on any standard syringe. During injection, the microneedle device was lightly pushed against the shoulder so that the microneedles penetrated the outmost layer of skin. The entire vaccine dose will then be injected causing a blanched bleb to appear. Intramuscular injection of conventional full-dose vaccine is given in the usual way with the prefilled syringe. Principal Investigator will be responsible for subject bleeding, serum separation, storing in doublet copies, freezing and archiving, according to HKU protocols.
MN and HI analysis (see below) shall be conducted by the HKU Laboratory according to the following protocols:
Microneutralization antibody assay (MN) NT will be performed inside a type II Biosafety Cabinet in a Biosafety Containment level III facility. NT will be performed in 96-well microtiter plates seeded with MDCK cells. Two fold serial dilutions of paired serum (pre- and post-vaccination) will be tested in duplicates against 100 TCID50 of the following 3 viruses: A/California/7/2009 (H1N1)pdm09-like virus; an A/Victoria/361/2011 (H3N2)-like virus; and a B/Wisconsin/1/2010-like virus in the presence of L-1-tosylamide-2-phenylethyl chloromethyl ketone (TPCK)-treated trypsin (TPCK-trypsin; Sigma). A corresponding set of cell controls with sera but without virus inoculation will be used as controls. The cells will be scored for the inhibition of the cytopathic effect (CPE) at 72~96 hours. The titer of neutralization antibody is defined as the maximum dilution of serum at which the percentage of CPE is less than or equal to 50%.
HI assay Serum samples will be tested for Hemagglutination inhibition (HI) antibody against the following: A/California/7/2009 (H1N1)pdm09-like virus; an A/Victoria/361/2011 (H3N2)-like virus; and a B/Wisconsin/1/2010-like virus using reference antigens (WHO influenza reagent kit provided by the World Health Organization influenza Collaborating Centre, CDC, Atlanta, Georgia, USA. HAI antibody assays will be performed by standard microtiter techniques after removal of non-specific inhibitors in serum with receptor destroying enzyme (RDE) (1:3), incubation overnight at 37 degree C followed by heat-inactivation at 56 degree C for 30 minutes. All serum samples from each subject will be tested for each of the test antigens. Serial two-fold dilutions of RDE-treated serum from 1:10 will be titrated against 4 hemagglutinin units of reference antigens using 0.25% turkey erythrocytes. A doublet backup of each serum sample would be prepared and frozen in two separately located freezers at -20ºC for potential future analysis and/or validation.
Outcome measures:
Primary outcome:
- Change from baseline (day 0 of vaccination )in neutralization antibody titre against influenza at day 21 and day 180 of vaccination
Secondary outcomes:
- Adverse effects at day 0-7
- Conditions
- Influenza, Human
- Being tested
- Intanza, Vaxigrip
- Keywords
- Influenza vaccine, intradermal, intramuscular, efficacy, safety
- Medical subject headings
- Influenza, Human
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IntanzaDrug
Also called Intanza, intradermal trivalent influenza vaccine
Principal Investigator would be responsible for injecting the intradermal vaccine in a sterile technique.
VaxigripDrug
Also called Vaxigrip, intramuscular trivalent influenza vaccine
Principal Investigator would be responsible for injecting the intrmuscular vaccine in a sterile technique.
| Study group | Role | What they receive |
|---|---|---|
| Intanza | Experimental | intradermal injection (15ug hemagglutinin 2013/2014 trivalent influenza vaccine) delivered with the Intanza, single dose injection Receives: Drug: Intanza |
| Vaxigrip | Active comparator | intramuscular injection (15ug hemagglutinin 2013/2014 trivalent influenza vaccine) delivered with the Vaxigrip, single dose injection Receives: Drug: Vaxigrip |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline in neutralization antibody titre against influenza
Neutralization antibody titre against the 3 influenza viruses are tested 3 times at day 0, day 21 and day 180 of vaccination for comparison. The titer of neutralization antibody is defined as the maximum dilution of serum at which the percentage of cytopathic effect is less than or equal to 50%.
Measured: day 0 (baseline), day 21 and day 180 of vaccination
Secondary outcomes (1)
Adverse effects
Adverse effects due to vaccination from day 0 to day 7 will be recorded. Adverse effects boardly divided into local and systemic. Local adverse effect include swelling, erythema, pruritis, pain. Systemic adverse effect include fever, malaise, myalgia
Measured: day 0 and day 7 of vaccination
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Oct 2013 (estimated)
- Study startOct 2013
- Primary completionMay 2014 (estimated)
- Study completionJun 2015 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Influenza, HumanStudies of the same condition, open and under way.
- More trials run by The University of Hong KongThe 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 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The University of Hong Kong
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dr. Chan Tuen Ching, The University of Hong Kong
- Investigators
- Tuen Ching Chan, MBBS, Principal investigator, The University of Hong Kong, Department of Medicine, Queen Mary Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01967368
- Sponsor's protocol ID
- UW 12339
- Status last verified
- Oct 2013
- First submitted
- 16 Oct 2013
- Last updated
- 22 Oct 2013
- Results posted
- No
- Data monitoring committee
- No
Publications
Chan TC, Hung IF, Chan KH, Li CP, Li PT, Luk JK, Chu LW, Chan FH. Immunogenicity and safety of intradermal trivalent influenza vaccination in nursing home older adults: a randomized controlled trial. J Am Med Dir Assoc. 2014 Aug;15(8):607.e5-12. doi: 10.1016/j.jamda.2014.05.002. Epub 2014 Jun 21.
PubMed 24957950
Study at a glance
From the registry record, last updated by the sponsor on 22 Oct 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Efficacy of Intradermal Trivalent Influenza Vaccination in Institutionalized Older Adults
- ClinicalTrials.gov ID
- NCT01967368
- Acronym / sponsor ID
- UW 12339
- Conditions
- Influenza, Human
- Keywords
- Influenza vaccine, intradermal, intramuscular, efficacy, safety
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- The University of Hong KongUniversity, hospital or other
- Study start
- Oct 2013
- Primary completion
- May 2014 (estimated)
- Study completion
- Jun 2015 (estimated)
- First posted
- 22 Oct 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Influenza is associated with significant morbidity and mortality. Institutionalized older adults (age>65) is the group associated with highest risk of complications. Influenza vaccines are the cornerstone of influenza prevention but one systematic review has found that there is no statistically significant difference against laboratory confirmed influenza. A major reason is immune senescence in older adults which result in weaker response towards vaccines when compared with young adults. Intradermal administration of vaccine has been suggested to improve immune response due to the abundance of immunostimulatory cells, such as dendritic cells in the dermis. Intradermal administration of influenza vaccine has been shown to have comparable or superior efficacy compared with intramuscular administration in the >60-year old population and the rates of adverse events post-vaccination were also comparable between them. The immunogenicity of intradermal administration has also been shown to be better in immunocompromised patients, including community dwelling older adults. In addition, intradermal vaccination has good acceptability and safety profile in different countries, so it has been licensed in Hong Kong and worldwide. However, there is little study regarding the efficacy of intradermal vaccination of influenza in institutionalized older adults, investigators therefore would like to perform a prospective, randomized study to compare the safety and immunogenicity between conventional full dose intramuscular immunization and full dose intradermal immunization of the trivalent influenza vaccine in institutionalized older adults.
The hypothesis is that full dose intradermal trivalent influenza vaccination is as effective as full-dose standard intramuscular injection in terms of seroconversion and seroprotection rate in institutionalized older adults. Finding of this study will be important in the vaccination of institutionalized older adults and immunocompromised patients as intradermal vaccine may induce a better immune response against influenza infection.
Detailed description
This is a prospective, randomized, parallel-group single centre trial in the Queen Mary Hospital and Fung Yiu King Hospital. Investigators aim to recruit 100 subjects who would be qualified for the Hospital Authority (HA)/ Centre for Health Protection (CHP) Mass Vaccination Program for Trivalent influenza vaccine (TIV). These patients include Institutionalized older adult patients at the age of 65 or above.
After informed consent (allow patient one week to consider) subjects will be randomly assigned into 2 groups to receive the following vaccines: Group 1: the full-dose (1 dose) standard TIV (15ug hemagglutinin TIV) delivered intramuscularly using a conventional needle, Group 2: a full-dose (1 dose) intradermal injection (15ug hemagglutinin TIV) delivered with the Intanza 15 at day 0. All TIV vaccines used in this study will be either of Vaxigrip® (Group 1) or Intanza® Intradermal (Group 2), Sanofi-Pasteur and provided by the Hospital Authority or the University of Hong Kong. Baseline HI to the TIV will be measured at day 0.
Patients fulfilling the inclusion criteria will be screened from the Community Geriatric Assessment Team (CGAT) of Fung Yiu King Hospital by the investigators. Before commencing, patients would be allowed to have one week to consider joining the study. Meanwhile, investigators would also take 5ml of serum from the participant to test for the baseline TIV antibody. Principal Investigator is experienced in administering intramuscular injections and he would be responsible for refilling the low-dose intradermal injection in a sterile technique. The microneedle device used in this study comprises an array of three 0.6 mm microneedles, made up of silicon crystal, and bonded to the tip of a plastic adapter, which can be mounted on any standard syringe. During injection, the microneedle device was lightly pushed against the shoulder so that the microneedles penetrated the outmost layer of skin. The entire vaccine dose will then be injected causing a blanched bleb to appear. Intramuscular injection of conventional full-dose vaccine is given in the usual way with the prefilled syringe. Principal Investigator will be responsible for subject bleeding, serum separation, storing in doublet copies, freezing and archiving, according to HKU protocols.
MN and HI analysis (see below) shall be conducted by the HKU Laboratory according to the following protocols:
Microneutralization antibody assay (MN) NT will be performed inside a type II Biosafety Cabinet in a Biosafety Containment level III facility. NT will be performed in 96-well microtiter plates seeded with MDCK cells. Two fold serial dilutions of paired serum (pre- and post-vaccination) will be tested in duplicates against 100 TCID50 of the following 3 viruses: A/California/7/2009 (H1N1)pdm09-like virus; an A/Victoria/361/2011 (H3N2)-like virus; and a B/Wisconsin/1/2010-like virus in the presence of L-1-tosylamide-2-phenylethyl chloromethyl ketone (TPCK)-treated trypsin (TPCK-trypsin; Sigma). A corresponding set of cell controls with sera but without virus inoculation will be used as controls. The cells will be scored for the inhibition of the cytopathic effect (CPE) at 72~96 hours. The titer of neutralization antibody is defined as the maximum dilution of serum at which the percentage of CPE is less than or equal to 50%.
HI assay Serum samples will be tested for Hemagglutination inhibition (HI) antibody against the following: A/California/7/2009 (H1N1)pdm09-like virus; an A/Victoria/361/2011 (H3N2)-like virus; and a B/Wisconsin/1/2010-like virus using reference antigens (WHO influenza reagent kit provided by the World Health Organization influenza Collaborating Centre, CDC, Atlanta, Georgia, USA. HAI antibody assays will be performed by standard microtiter techniques after removal of non-specific inhibitors in serum with receptor destroying enzyme (RDE) (1:3), incubation overnight at 37 degree C followed by heat-inactivation at 56 degree C for 30 minutes. All serum samples from each subject will be tested for each of the test antigens. Serial two-fold dilutions of RDE-treated serum from 1:10 will be titrated against 4 hemagglutinin units of reference antigens using 0.25% turkey erythrocytes. A doublet backup of each serum sample would be prepared and frozen in two separately located freezers at -20ºC for potential future analysis and/or validation.
Outcome measures:
Primary outcome:
- Change from baseline (day 0 of vaccination )in neutralization antibody titre against influenza at day 21 and day 180 of vaccination
Secondary outcomes:
- Adverse effects at day 0-7
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intanza | Experimental | Drug: Intanzaintradermal injection (15ug hemagglutinin 2013/2014 trivalent influenza vaccine) delivered with the Intanza, single dose injection |
| Vaxigrip | Active comparator | Drug: Vaxigripintramuscular injection (15ug hemagglutinin 2013/2014 trivalent influenza vaccine) delivered with the Vaxigrip, single dose injection |
Who may qualify
- Ages
- 65 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Older adult
Key inclusion criteria (1 listed)
- Institutionalized older adult patients at the age of 65 or above
Key exclusion criteria (1 listed)
- Clinically significant immune-related diseases and significant recent co-morbidities
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 |
|---|---|---|
| IntanzaAlso: Intanza, intradermal trivalent influenza vaccinePrincipal Investigator would be responsible for injecting the intradermal vaccine in a sterile technique. | Drug | Intanza |
| VaxigripAlso: Vaxigrip, intramuscular trivalent influenza vaccinePrincipal Investigator would be responsible for injecting the intrmuscular vaccine in a sterile technique. | Drug | Vaxigrip |
Primary outcome
Change from baseline in neutralization antibody titre against influenza
Time frame: day 0 (baseline), day 21 and day 180 of vaccination
Neutralization antibody titre against the 3 influenza viruses are tested 3 times at day 0, day 21 and day 180 of vaccination for comparison. The titer of neutralization antibody is defined as the maximum dilution of serum at which the percentage of cytopathic effect is less than or equal to 50%.
1 secondary outcome
Adverse effects
Time frame: day 0 and day 7 of vaccination
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Oct 2013.
- Derived from this study: PubMed 24957950Chan TC, Hung IF, Chan KH, Li CP, Li PT, Luk JK, Chu LW, Chan FH. Immunogenicity and safety of intradermal trivalent influenza vaccination in nursing home older adults: a randomized controlled trial. J Am Med Dir Assoc. 2014 Aug;15(8):607.e5-12. doi: 10.1016/j.jamda.2014.05.002. Epub 2014 Jun 21.
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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.
Tuen Ching Chan, MBBS principal investigator
The University of Hong Kong, Department of Medicine, Queen Mary Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Intanza and Vaxigrip in people with Influenza, Human, run by The University of Hong Kong at 1 site in China.
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 1 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: status not confirmed, as of the sponsor's last update on 22 Oct 2013. 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 China. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Tuen Ching Chan, MBBS (85266816077, tuenching@yahoo.com.hk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change from baseline in neutralization antibody titre against influenza (time frame: day 0 (baseline), day 21 and day 180 of vaccination). 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 NCT01967368, 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 22 Oct 2013.