PneumoniaPhase 3NCT01319955
Flu Vaccine Against Childhood Pneumonia, Bangladesh
A Phase 3 study testing Trivalent inactivated influenza vaccine in people with Pneumonia and Laboratory Confirmed Influenza, run by International Centre for Diarrhoeal Disease Research, Bangladesh at 1 site in Bangladesh.
Trial summary
Pneumonia is the leading cause of child death worldwide. Data from Bangladesh indicates that influenza has a substantial association with pneumonia among children less than two years old. Read more about this study
- Who is it for?
- Ages 6 to 23 monthsHealthy volunteers can take part
- Conditions the study is for
- Pneumonia, Laboratory Confirmed Influenza
- What is being tested?
- Trivalent inactivated influenza vaccine
- Type of treatment
- Vaccines
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3,508 participants
- Where
- 1 siteBangladesh
- Study dates
- Aug 2010to Apr 2017
- Phase
- Phase 3
- 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 6 to 23 months
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- Children will be included if they are de jure residents 6 months to 23 months old at the time of first dose vaccination residing in households under surveillance.
Who cannot join
- Children will be excluded if they have known chronic respiratory, cardiac, or neurological (including seizure disorders) illnesses, are severely malnourished or require hospitalisation for any other reason, are suspected of having tuberculosis (WHO guidelines) [83], are known to have egg allergy, or parents withhold consent.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Influenza Vaccine Efficacy Against Childhood Pneumonia in an Urban Tropical Setting
Pneumonia is the leading cause of child death worldwide. Data from Bangladesh indicates that influenza has a substantial association with pneumonia among children less than two years old. This study will use commercially available trivalent inactivated vaccine (killed vaccine) to see if it can prevent early childhood pneumonia among children less than two years old. The study will vaccinate children across three seasons (3 years), and look at the effect on the attack rate of pneumonia, as well as its effects on laboratory-confirmed influenza. It will also look at the effect on laboratory-confirmed influenza illness among the non-vaccinated household contacts of all ages of these children.
Read the detailed description
Pneumonia is the primary cause of child mortality worldwide. The global community is considering interventions to reduce pneumonia burden, including vaccines. Most attention is focused on bacterial vaccines. Influenza vaccine has not received attention due to lack of influenza burden data from high pneumonia endemic settings, and poor understanding of how influenza contributes, independently and with other pathogens, to childhood pneumonia burden. Data from Bangladesh indicate that influenza has a high incidence of over 10% per year among children < 5 years, and that among children who get influenza infection, 28% develop pneumonia, including severe pneumonia. Influenza-infected children who develop pneumonia are significantly younger (< 2y) than those who do not. Due to the high influenza incidence, and the high proportion of influenza-infected children who develop pneumonia, influenza is a major contributor to childhood pneumonia, not only in Bangladesh, but likely throughout the pneumonia endemic tropical and sub-tropical belt. Although trials have been conducted to examine influenza vaccine impact on influenza, none have been conducted specifically to determine the effect on childhood pneumonia, particularly among those < 2 years who are at highest pneumonia risk. We propose to conduct such a trial.
The project goal is to determine whether influenza vaccine (trivalent inactivated vaccine or TIV) can reduce childhood pneumonia burden including: influenza-associated, other aetiology-mediated, and overall pneumonia incidence. The specific objectives are to determine influenza vaccine efficacy on 1) early childhood pneumonia (children < 2 years), 2) laboratory-confirmed influenza and 3) the rates of influenza-specific complications including severe disease, hospitalisation, and otitis media. Secondary objectives include determining the effect of influenza vaccine on household transmission and associated complications among all age groups, the effect on proven non-influenza viral and bacterial invasive diseases, the occurrence of adverse events associated with the vaccine, and to measure immune responsiveness to influenza vaccine in these young children.
Critical milestones include comparison between vaccinated and vaccine-controlled children of 1) pneumonia incidence (vaccine efficacy against pneumonia), 2) influenza incidence (vaccine efficacy against influenza) 3) rates of other clinical syndromes (vaccine efficacy against other childhood morbidity). Milestones related to secondary objectives include comparison between vaccinated and vaccine-controlled children of 1) rates of laboratory-confirmed infection and clinical illness among household contacts and 2) rates of other invasive bacterial and viral diseases, and 3) rates of adverse events. We will also measure childhood immune responsiveness to influenza vaccine and relate that to observed rates of infection and clinical illness.
- Conditions
- Pneumonia, Laboratory Confirmed Influenza
- Being tested
- Trivalent inactivated influenza vaccine
- Keywords
- Pneumonia, Influenza, Child, Respiratory, Pathogen
- Medical subject headings
- Pneumonia, Influenza, Human
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Trivalent inactivated influenza vaccineBiological
Also called Vaxigrip Junior
Two doses of 0.25 ml vaccine delivered IM at least 4 weeks apart.
| Study group | Role | What they receive |
|---|---|---|
| Influenza vaccine (trivalent inactivated vaccine) | Experimental | Not described Receives: Biological: Trivalent inactivated influenza vaccine |
| Inactivated polio vaccine | Active comparator | Not described Receives: Biological: Trivalent inactivated influenza vaccine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical pneumonia
Children who present with age-specific tachypnoea, cough with crepitations on auscultation will be determined to have clinical pneumonia. If this occurs ≥14 days post two doses of influenza vaccine, they will be considered fully vaccinated. Comparisons will be made between groups on the number of such episodes.
Measured: Up to 12 months post-vaccination
Laboratory confirmed influenza infection
Influenza infection will be determined by RT-PCR among children with signs and symptoms of febrile and/or respiratory symptoms, including pneumonia.
Measured: Up to 12 months post-vaccination
Secondary outcomes (5)
Indirect effects
Laboratory-confirmed influenza will assessed by RT-PCR among household contacts who present with signs and symptoms of febrile and/or respiratory illness.
Measured: Up to 12 months post-vaccination
Epidemiological and clinical characteristics of influenza infection
The epidemiological (seasonality and incidence) and clinical (important clinical syndromes, clinical course, complications and outcomes) characteristics of laboratory-confirmed influenza infection in this age group will be documented.
Measured: Up to 12 months post vaccination
Effect on non-influenza viral and bacterial invasive disease
We will measure the influenza vaccine effect on invasive disease by other pathogens, including pneumococcus, Haemophilus, and several respiratory viruses.
Measured: Up to 12 months post vaccination
Immunogenicity
We will obtain serum on a 20% subsample of children pre-dose 1, pre-dose 2 and 4 weeks post-dose 2 to determine the immune responsiveness to the vaccine.
Measured: Within 4 months of vaccine administration
Adverse events associated with the vaccine
Adverse events will be monitored, beginning the day of vaccination and for the next 7 days (8 time points) using standardised questionnaires.
Measured: Beginning Day 0 (day of vaccination) and for the next 7 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Mar 2011 (estimated)
- Study startAug 2010
- Primary completionApr 2017
- Study completionApr 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for PneumoniaStudies of the same condition, open and under way.
- 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 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 3,508 participants (actual)
Sponsor and investigators
- Lead sponsor
- International Centre for Diarrhoeal Disease Research, Bangladesh
- Sponsor type
- University, hospital or other
- Collaborators
- Johns Hopkins University, Centers for Disease Control and Prevention
- Responsible party
- Sponsor
- Investigators
- W. Abdullah Brooks, MD, MPH, Principal investigator, International Centre for Diarrhoeal Disease Research, Bangladesh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01319955
- Sponsor's protocol ID
- PR-09054
- Other IDs
- 00002579
- Status last verified
- Aug 2016
- First submitted
- 9 Mar 2011
- Last updated
- 25 Sep 2017
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Brooks WA, Goswami D, Rahman M, Nahar K, Fry AM, Balish A, Iftekharuddin N, Azim T, Xu X, Klimov A, Bresee J, Bridges C, Luby S. Influenza is a major contributor to childhood pneumonia in a tropical developing country. Pediatr Infect Dis J. 2010 Mar;29(3):216-21. doi: 10.1097/INF.0b013e3181bc23fd.
PubMed 20190613Rolfes MA, Goswami D, Sharmeen AT, Yeasmin S, Parvin N, Nahar K, Rahman M, Barends M, Ahmed D, Rahman MZ, Bresee J, Luby S, Moulton LH, Santosham M, Fry AM, Brooks WA. Efficacy of trivalent influenza vaccine against laboratory-confirmed influenza among young children in a randomized trial in Bangladesh. Vaccine. 2017 Dec 15;35(50):6967-6976. doi: 10.1016/j.vaccine.2017.10.074. Epub 2017 Oct 31.
PubMed 29100706
Study at a glance
From the registry record, last updated by the sponsor on 25 Sep 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Influenza Vaccine Efficacy Against Childhood Pneumonia in an Urban Tropical Setting
- ClinicalTrials.gov ID
- NCT01319955
- Acronym / sponsor ID
- PR-09054
- Conditions
- Pneumonia, Laboratory Confirmed Influenza
- Keywords
- Pneumonia, Influenza, Child, Respiratory, Pathogen
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 3,508 participants (actual)
- Lead sponsor
- International Centre for Diarrhoeal Disease Research, BangladeshUniversity, hospital or other
- Collaborators
- Johns Hopkins University, Centers for Disease Control and Prevention
- Study start
- Aug 2010
- Primary completion
- Apr 2017 (actual)
- Study completion
- Apr 2017 (actual)
- First posted
- 22 Mar 2011 (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.
Pneumonia is the leading cause of child death worldwide. Data from Bangladesh indicates that influenza has a substantial association with pneumonia among children less than two years old. This study will use commercially available trivalent inactivated vaccine (killed vaccine) to see if it can prevent early childhood pneumonia among children less than two years old. The study will vaccinate children across three seasons (3 years), and look at the effect on the attack rate of pneumonia, as well as its effects on laboratory-confirmed influenza. It will also look at the effect on laboratory-confirmed influenza illness among the non-vaccinated household contacts of all ages of these children.
Detailed description
Pneumonia is the primary cause of child mortality worldwide. The global community is considering interventions to reduce pneumonia burden, including vaccines. Most attention is focused on bacterial vaccines. Influenza vaccine has not received attention due to lack of influenza burden data from high pneumonia endemic settings, and poor understanding of how influenza contributes, independently and with other pathogens, to childhood pneumonia burden. Data from Bangladesh indicate that influenza has a high incidence of over 10% per year among children < 5 years, and that among children who get influenza infection, 28% develop pneumonia, including severe pneumonia. Influenza-infected children who develop pneumonia are significantly younger (< 2y) than those who do not. Due to the high influenza incidence, and the high proportion of influenza-infected children who develop pneumonia, influenza is a major contributor to childhood pneumonia, not only in Bangladesh, but likely throughout the pneumonia endemic tropical and sub-tropical belt. Although trials have been conducted to examine influenza vaccine impact on influenza, none have been conducted specifically to determine the effect on childhood pneumonia, particularly among those < 2 years who are at highest pneumonia risk. We propose to conduct such a trial.
The project goal is to determine whether influenza vaccine (trivalent inactivated vaccine or TIV) can reduce childhood pneumonia burden including: influenza-associated, other aetiology-mediated, and overall pneumonia incidence. The specific objectives are to determine influenza vaccine efficacy on 1) early childhood pneumonia (children < 2 years), 2) laboratory-confirmed influenza and 3) the rates of influenza-specific complications including severe disease, hospitalisation, and otitis media. Secondary objectives include determining the effect of influenza vaccine on household transmission and associated complications among all age groups, the effect on proven non-influenza viral and bacterial invasive diseases, the occurrence of adverse events associated with the vaccine, and to measure immune responsiveness to influenza vaccine in these young children.
Critical milestones include comparison between vaccinated and vaccine-controlled children of 1) pneumonia incidence (vaccine efficacy against pneumonia), 2) influenza incidence (vaccine efficacy against influenza) 3) rates of other clinical syndromes (vaccine efficacy against other childhood morbidity). Milestones related to secondary objectives include comparison between vaccinated and vaccine-controlled children of 1) rates of laboratory-confirmed infection and clinical illness among household contacts and 2) rates of other invasive bacterial and viral diseases, and 3) rates of adverse events. We will also measure childhood immune responsiveness to influenza vaccine and relate that to observed rates of infection and clinical illness.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Influenza vaccine (trivalent inactivated vaccine) | Experimental | Biological: Trivalent inactivated influenza vaccine |
| Inactivated polio vaccine | Active comparator | Biological: Trivalent inactivated influenza vaccine |
Who may qualify
- Ages
- 6 to 23 months
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (1 listed)
- Children will be included if they are de jure residents 6 months to 23 months old at the time of first dose vaccination residing in households under surveillance.
Key exclusion criteria (1 listed)
- Children will be excluded if they have known chronic respiratory, cardiac, or neurological (including seizure disorders) illnesses, are severely malnourished or require hospitalisation for any other reason, are suspected of having tuberculosis (WHO guidelines) [83], are known to have egg allergy, or parents withhold consent.
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 |
|---|---|---|
| Trivalent inactivated influenza vaccineAlso: Vaxigrip JuniorTwo doses of 0.25 ml vaccine delivered IM at least 4 weeks apart. | Biological | Inactivated polio vaccine, Influenza vaccine (trivalent inactivated vaccine) |
Primary outcome
Clinical pneumonia
Time frame: Up to 12 months post-vaccination
Children who present with age-specific tachypnoea, cough with crepitations on auscultation will be determined to have clinical pneumonia. If this occurs ≥14 days post two doses of influenza vaccine, they will be considered fully vaccinated. Comparisons will be made between groups on the number of such episodes.
Laboratory confirmed influenza infection
Time frame: Up to 12 months post-vaccination
Influenza infection will be determined by RT-PCR among children with signs and symptoms of febrile and/or respiratory symptoms, including pneumonia.
5 secondary outcomes
Indirect effects
Time frame: Up to 12 months post-vaccination
Epidemiological and clinical characteristics of influenza infection
Time frame: Up to 12 months post vaccination
Effect on non-influenza viral and bacterial invasive disease
Time frame: Up to 12 months post vaccination
Immunogenicity
Time frame: Within 4 months of vaccine administration
Adverse events associated with the vaccine
Time frame: Beginning Day 0 (day of vaccination) and for the next 7 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Sep 2017.
- Background: PubMed 20190613Brooks WA, Goswami D, Rahman M, Nahar K, Fry AM, Balish A, Iftekharuddin N, Azim T, Xu X, Klimov A, Bresee J, Bridges C, Luby S. Influenza is a major contributor to childhood pneumonia in a tropical developing country. Pediatr Infect Dis J. 2010 Mar;29(3):216-21. doi: 10.1097/INF.0b013e3181bc23fd.
- Derived from this study: PubMed 29100706Rolfes MA, Goswami D, Sharmeen AT, Yeasmin S, Parvin N, Nahar K, Rahman M, Barends M, Ahmed D, Rahman MZ, Bresee J, Luby S, Moulton LH, Santosham M, Fry AM, Brooks WA. Efficacy of trivalent influenza vaccine against laboratory-confirmed influenza among young children in a randomized trial in Bangladesh. Vaccine. 2017 Dec 15;35(50):6967-6976. doi: 10.1016/j.vaccine.2017.10.074. Epub 2017 Oct 31.
Related trials for Pneumonia
Not yet recruitingPhase 1
Phase I Open-Label Safety Trial of Pembrolizumab for Neurological Post- Acute Sequelae of SARS-CoV-2 (PD1-PASC I)
Post-Acute COVID-19 Syndrome
Not yet recruitingPhase 2/3
A Pivotal Safety and Immunogenicity GBS-NN/NN2 Vaccine Maternal Immunisation Trial
Streptococcus Agalactiae Infection, Neonatal Sepsis
Active, not recruitingPhase 1
A Safety and Immunogenicity Trial of OCU500, ChAd36 Vector Encoding SARS-CoV-2 Spike Vaccine Via Intranasal and Inhalational Routes in Previously Vaccinated Adults
COVID-19
Enrolling by invitation
Personalized Ventilator Settings for Patients on ECMO
Acute Respiratory Distress Syndrome (ARDS), Extracorporeal Membrane Oxygenation
Not yet recruiting
Expanded Diagnostic Strategy in Older Adults Hospitalized With Community-Acquired Acute Respiratory Infection
Acute Respiratory Infection
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.
W. Abdullah Brooks, MD, MPH principal investigator
International Centre for Diarrhoeal Disease Research, Bangladesh
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Trivalent inactivated influenza vaccine in people with Pneumonia and Laboratory Confirmed Influenza, run by International Centre for Diarrhoeal Disease Research, Bangladesh at 1 site in Bangladesh.
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: finished, as of the sponsor's last update on 25 Sep 2017. 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 Bangladesh. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Clinical pneumonia (time frame: Up to 12 months post-vaccination). The study lists 2 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 NCT01319955, which also lists 2 linked publications.
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 25 Sep 2017.