InfluenzaPhase 4NCT01194297
Study of Live, Attenuated Influenza Vaccination in Preterm and Full-Term Infants
A Phase 4 study testing Live attenuated influenza vaccine and Inactivated influenza vaccine in people with Influenza, run by University of Rochester.
Trial summary
Severe influenza respiratory disease is increasingly recognized in children. Influenza hospitalization rates in high-risk infants, such as premature infants, are increased some five-fold over rates in other children. Read more about this study
- Who is it for?
- Ages 24 to 35 monthsHealthy volunteers can take part
- Conditions the study is for
- Influenza
- What is being tested?
- Live attenuated influenza vaccine and Inactivated influenza vaccine
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- No sites listed yet
- Study dates
- Aug 2010to May 2012
- Phase
- Phase 4
- 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 24 to 35 months
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- Subjects must meet all relevant criteria (by time of influenza vaccination) to participate.
- (a) Former premature (<32 weeks' gestation at birth), VLBW (<1500 grams' birth weight) infant, 24 months, 0 days - 35 months, 31 days of age, OR (b) Former full-term (37-42 weeks' gestation at birth), normal birth weight (>2500 grams' birth weight) infant, 24 months, 0 days - 35 months, 31 days of age.
- Influenza immunization in prior season.
- Eligible for either influenza immunization (TIV or LAIV).
- Parental permission.
- Parents likely to be able to comply with study visits.
Who cannot join
- Subjects may not participate if they meet any one of these criteria.
- Known immunodeficiency in child or in a close household contact.
- History of:
- Recurrent episodes of wheezing,
- Medically-attended wheezing illness in past year, or
- Hospitalization for a wheezing illness.
Show all 11Show fewer
- Systemic corticosteroid administration at time of influenza vaccination.
- Requiring supplemental oxygen at time of influenza vaccination.
- Contraindication to either influenza immunization (e.g. egg allergy, aspirin therapy).
- Physician-diagnosed influenza illness in the current influenza season.
- Any condition determined by investigator as likely to interfere with evaluation of the vaccine or be a significant potential health risk to the subject.
About this study
Official title: Immune Responses in Preterm and Full-Term Infants Following Live, Attenuated Influenza Vaccination
Severe influenza respiratory disease is increasingly recognized in children. Influenza hospitalization rates in high-risk infants, such as premature infants, are increased some five-fold over rates in other children. The recently-licensed live attenuated influenza vaccine (LAIV) promotes better immune responses than the trivalent inactivated vaccine, but can cause wheezing. The balance of risks and benefits for LAIV in extremely premature infants, who may be at increased risk for both influenza disease and vaccine side effects, is unknown.
The specific aim of this project is to compare the immune response and reactions of trivalent, inactivated influenza vaccine (TIV) and live, attenuated, intranasal influenza vaccine (LAIV) in groups of former premature (PT), very (V) LBW and former full-term (FT) infants aged 24-35 months.
Read more
The investigators hypothesize that the immune response in FT infants will be greater with LAIV than TIV, and that wheezing episodes will be no more than twice as frequent in LAIV as in TIV recipients.
The study will enroll 14 former premature, VLBW infants and 14 former full-term infants. Children will be randomized to receive one dose either TIV or LAIV. Vaccine reactions will be measured. One to two teaspoons mL of blood will be drawn at 0 and 7-14 days from immunization, and less than one teaspoon of blood will be drawn at 28-42 days.
Read the detailed description
Background. Influenza infection causes an estimated 1 million deaths worldwide yearly. Severe influenza respiratory disease is increasingly recognized in children. Influenza hospitalization rates in high-risk infants, such as premature infants, are increased some five-fold over rates in other children. Influenza vaccine immunogenicity is generally modest even in healthy children, and influenza vaccines have been incompletely studied in premature infants. The recently-licensed live attenuated influenza vaccine (LAIV) is more immunogenic than the trivalent inactivated vaccine, but its use in infants and high risk children is limited by side effects. The risk/benefit ratio of LAIV in extremely premature infants, who may be at increased risk for both influenza disease and vaccine side effects, is unknown.
Aim. The specific aim of this project is to compare the immunogenicity and reactogenicity of trivalent, inactivated influenza vaccine (TIV) and live, attenuated, intranasal influenza vaccine (LAIV) in groups of former premature (PT), very low birth weight (VLBW) and former full-term (FT) infants aged 24-35 months.
Hypotheses.
- The humoral immunogenicity of LAIV, as measured by hemagglutination inhibition (HI), will be greater than that of TIV. This will be the co-primary outcome for this study.
- Vaccine reactogenicity, as measured by medically-attended wheezing episodes, will be no more than twice as frequent in LAIV as in TIV recipients. This will be the co-primary outcome for this study.
- Functional B-cell responses, as measured by antibody secreting cell (ASC) enzyme linked immunospot (ELISPOT), will be greater in LAIV-immunized infants than TIV-immunized infants.
- Peak T-cell cytokine responses, as measured by interferon gamma (IFNγ), interleukin (IL)-2 and IL-4 ELISPOT, will be greater in LAIV-immunized infants than TIV-immunized infants.
- Hemagglutinin-specific nasal immunoglobulin A (IgA) will be measureable following LAIV immunization.
- Former premature infants will have similar adaptive immune responses, but elevated reactogenicity to both vaccines, when compared to former full-term infants.
Design. The study will enroll 14 former premature, VLBW infants and 14 former full-term infants. Subjects, who will be eligible to receive either TIV or LAIV as part of routine care, will be randomized to receive one dose either TIV or LAIV, according to prevailing recommendations for influenza immunization. Randomization will be stratified by prematurity status. Vaccine reactogenicity will be measured by using parent diaries following immunization and questionnaires at each visit. Five to 10 mL of blood will be drawn at 0 and 7-14 days from immunization for isolation of peripheral blood mononuclear cells (PBMC), and 1 mL of blood will be drawn for serum separation for antibody determination at 0 and 28-42 days. Antibody levels and T- and B-cell responses to vaccine will be measured.
Potential Impact. This study is designed to assess the immunogenicity and reactogenicity of two current influenza vaccines in premature infants. The data will be used to estimate the sample size for a definitive trial in younger premature infants.
- Conditions
- Influenza
- Being tested
- Live attenuated influenza vaccine, Inactivated influenza vaccine
- Keywords
- influenza, premature infant, very low birth weight infant, immunization, vaccine
- Medical subject headings
- Influenza, Human, Premature Birth
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Live attenuated influenza vaccineBiological
Also called FluMist
One dose of live attenuated influenza vaccine, according to routine immunization recommendations
Inactivated influenza vaccineBiological
Also called Fluzone
One dose of inactivated influenza vaccine, according to routine immunization recommendations
| Study group | Role | What they receive |
|---|---|---|
| Live attenuated influenza vaccine | Experimental | One dose of live attenuated influenza vaccine, according to routine immunization recommendations Receives: Biological: Live attenuated influenza vaccine |
| Inactivated influenza vaccine | Active comparator | One dose of inactivated influenza vaccine, according to routine immunization recommendations Receives: Biological: Inactivated influenza vaccine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Humoral Immunogenicity
Hemagglutinin specific antibody, as measured by hemagglutination inhibition
Measured: 28-42 days
Secondary outcomes (1)
Medically-attended Wheezing
Wheezing that triggers a visit for medical care
Measured: 42 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Sep 2010 (estimated)
- Study startAug 2010
- Primary completionMay 2012
- Study completionMay 2012
Why it stopped: Insufficient enrollment
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.
- Other trials for InfluenzaStudies of the same condition, open and under way.
- More trials run by University of RochesterThe 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
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Rochester
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Carl D'Angio, University of Rochester
- Investigators
- Carl T. D'Angio, MD, Principal investigator, University of Rochester
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01194297
- Sponsor's protocol ID
- 25914
- Status last verified
- Aug 2014
- First submitted
- 31 Aug 2010
- Last updated
- 22 Aug 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Aug 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Immune Responses in Preterm and Full-Term Infants Following Live, Attenuated Influenza Vaccination
- ClinicalTrials.gov ID
- NCT01194297
- Acronym / sponsor ID
- 25914
- Conditions
- Influenza
- Keywords
- influenza, premature infant, very low birth weight infant, immunization, vaccine
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Insufficient enrollment
- Enrolment
- 3 participants (actual)
- Lead sponsor
- University of RochesterUniversity, hospital or other
- Study start
- Aug 2010
- Primary completion
- May 2012 (actual)
- Study completion
- May 2012 (actual)
- First posted
- 2 Sep 2010 (estimated)
- Results
- Posted 22 Aug 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Severe influenza respiratory disease is increasingly recognized in children. Influenza hospitalization rates in high-risk infants, such as premature infants, are increased some five-fold over rates in other children. The recently-licensed live attenuated influenza vaccine (LAIV) promotes better immune responses than the trivalent inactivated vaccine, but can cause wheezing. The balance of risks and benefits for LAIV in extremely premature infants, who may be at increased risk for both influenza disease and vaccine side effects, is unknown.
The specific aim of this project is to compare the immune response and reactions of trivalent, inactivated influenza vaccine (TIV) and live, attenuated, intranasal influenza vaccine (LAIV) in groups of former premature (PT), very (V) LBW and former full-term (FT) infants aged 24-35 months.
The investigators hypothesize that the immune response in FT infants will be greater with LAIV than TIV, and that wheezing episodes will be no more than twice as frequent in LAIV as in TIV recipients.
The study will enroll 14 former premature, VLBW infants and 14 former full-term infants. Children will be randomized to receive one dose either TIV or LAIV. Vaccine reactions will be measured. One to two teaspoons mL of blood will be drawn at 0 and 7-14 days from immunization, and less than one teaspoon of blood will be drawn at 28-42 days.
Detailed description
Background. Influenza infection causes an estimated 1 million deaths worldwide yearly. Severe influenza respiratory disease is increasingly recognized in children. Influenza hospitalization rates in high-risk infants, such as premature infants, are increased some five-fold over rates in other children. Influenza vaccine immunogenicity is generally modest even in healthy children, and influenza vaccines have been incompletely studied in premature infants. The recently-licensed live attenuated influenza vaccine (LAIV) is more immunogenic than the trivalent inactivated vaccine, but its use in infants and high risk children is limited by side effects. The risk/benefit ratio of LAIV in extremely premature infants, who may be at increased risk for both influenza disease and vaccine side effects, is unknown.
Aim. The specific aim of this project is to compare the immunogenicity and reactogenicity of trivalent, inactivated influenza vaccine (TIV) and live, attenuated, intranasal influenza vaccine (LAIV) in groups of former premature (PT), very low birth weight (VLBW) and former full-term (FT) infants aged 24-35 months.
Hypotheses.
- The humoral immunogenicity of LAIV, as measured by hemagglutination inhibition (HI), will be greater than that of TIV. This will be the co-primary outcome for this study.
- Vaccine reactogenicity, as measured by medically-attended wheezing episodes, will be no more than twice as frequent in LAIV as in TIV recipients. This will be the co-primary outcome for this study.
- Functional B-cell responses, as measured by antibody secreting cell (ASC) enzyme linked immunospot (ELISPOT), will be greater in LAIV-immunized infants than TIV-immunized infants.
- Peak T-cell cytokine responses, as measured by interferon gamma (IFNγ), interleukin (IL)-2 and IL-4 ELISPOT, will be greater in LAIV-immunized infants than TIV-immunized infants.
- Hemagglutinin-specific nasal immunoglobulin A (IgA) will be measureable following LAIV immunization.
- Former premature infants will have similar adaptive immune responses, but elevated reactogenicity to both vaccines, when compared to former full-term infants.
Design. The study will enroll 14 former premature, VLBW infants and 14 former full-term infants. Subjects, who will be eligible to receive either TIV or LAIV as part of routine care, will be randomized to receive one dose either TIV or LAIV, according to prevailing recommendations for influenza immunization. Randomization will be stratified by prematurity status. Vaccine reactogenicity will be measured by using parent diaries following immunization and questionnaires at each visit. Five to 10 mL of blood will be drawn at 0 and 7-14 days from immunization for isolation of peripheral blood mononuclear cells (PBMC), and 1 mL of blood will be drawn for serum separation for antibody determination at 0 and 28-42 days. Antibody levels and T- and B-cell responses to vaccine will be measured.
Potential Impact. This study is designed to assess the immunogenicity and reactogenicity of two current influenza vaccines in premature infants. The data will be used to estimate the sample size for a definitive trial in younger premature infants.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Live attenuated influenza vaccine | Experimental | Biological: Live attenuated influenza vaccineOne dose of live attenuated influenza vaccine, according to routine immunization recommendations |
| Inactivated influenza vaccine | Active comparator | Biological: Inactivated influenza vaccineOne dose of inactivated influenza vaccine, according to routine immunization recommendations |
Who may qualify
- Ages
- 24 to 35 months
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (6 listed)
- Subjects must meet all relevant criteria (by time of influenza vaccination) to participate.
- (a) Former premature (<32 weeks' gestation at birth), VLBW (<1500 grams' birth weight) infant, 24 months, 0 days - 35 months, 31 days of age, OR (b) Former full-term (37-42 weeks' gestation at birth), normal birth weight (>2500 grams' birth weight) infant, 24 months, 0 days - 35 months, 31 days of age.
- Influenza immunization in prior season.
- Eligible for either influenza immunization (TIV or LAIV).
- Parental permission.
Key exclusion criteria (11 listed)
- Subjects may not participate if they meet any one of these criteria.
- Known immunodeficiency in child or in a close household contact.
- History of:
- Systemic corticosteroid administration at time of influenza vaccination.
- Requiring supplemental oxygen at time of influenza vaccination.
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 |
|---|---|---|
| Live attenuated influenza vaccineAlso: FluMistOne dose of live attenuated influenza vaccine, according to routine immunization recommendations | Biological | Live attenuated influenza vaccine |
| Inactivated influenza vaccineAlso: FluzoneOne dose of inactivated influenza vaccine, according to routine immunization recommendations | Biological | Inactivated influenza vaccine |
Primary outcome
Humoral Immunogenicity
Time frame: 28-42 days
Hemagglutinin specific antibody, as measured by hemagglutination inhibition
1 secondary outcome
Medically-attended Wheezing
Time frame: 42 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Aug 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Carl T. D'Angio, MD principal investigator
University of Rochester
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Live attenuated influenza vaccine and Inactivated influenza vaccine in people with Influenza, run by University of Rochester.
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 6 inclusion and 11 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: stopped early, as of the sponsor's last update on 22 Aug 2014. Status can change between updates, so confirm with the study contact before making plans.
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?
Yes. Results are posted in the registry (first posted 22 Aug 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?
Humoral Immunogenicity (time frame: 28-42 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 Aug 2014.