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Flu Vaccine Against Childhood Pneumonia, Bangladesh

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2010 by International Centre for Diarrhoeal Disease Research, Bangladesh
Sponsor:
Collaborators:
Johns Hopkins University
Information provided by (Responsible Party):
International Centre for Diarrhoeal Disease Research, Bangladesh
ClinicalTrials.gov Identifier:
NCT01319955
First received: March 9, 2011
Last updated: July 9, 2014
Last verified: April 2010
  Purpose

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.


Condition Intervention Phase
Pneumonia
Laboratory Confirmed Influenza
Biological: Trivalent inactivated influenza vaccine
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Influenza Vaccine Efficacy Against Childhood Pneumonia in an Urban Tropical Setting

Resource links provided by NLM:


Further study details as provided by International Centre for Diarrhoeal Disease Research, Bangladesh:

Primary Outcome Measures:
  • Clinical pneumonia [ Time Frame: Up to 12 months post-vaccination ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    Influenza infection will be determined by RT-PCR among children with signs and symptoms of febrile and/or respiratory symptoms, including pneumonia.


Secondary Outcome Measures:
  • Indirect effects [ Time Frame: Up to 12 months post-vaccination ] [ Designated as safety issue: No ]
    Laboratory-confirmed influenza will assessed by RT-PCR among household contacts who present with signs and symptoms of febrile and/or respiratory illness.

  • Epidemiological and clinical characteristics of influenza infection [ Time Frame: Up to 12 months post vaccination ] [ Designated as safety issue: No ]
    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.

  • Effect on non-influenza viral and bacterial invasive disease [ Time Frame: Up to 12 months post vaccination ] [ Designated as safety issue: No ]
    We will measure the influenza vaccine effect on invasive disease by other pathogens, including pneumococcus, Haemophilus, and several respiratory viruses.

  • Immunogenicity [ Time Frame: Within 4 months of vaccine administration ] [ Designated as safety issue: No ]
    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.

  • Adverse events associated with the vaccine [ Time Frame: Beginning Day 0 (day of vaccination) and for the next 7 days ] [ Designated as safety issue: Yes ]
    Adverse events will be monitored, beginning the day of vaccination and for the next 7 days (8 time points) using standardised questionnaires.


Estimated Enrollment: 3408
Study Start Date: August 2010
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Influenza vaccine (trivalent inactivated vaccine) Biological: Trivalent inactivated influenza vaccine
Two doses of 0.25 ml vaccine delivered IM at least 4 weeks apart.
Other Name: Vaxigrip Junior
Active Comparator: Inactivated polio vaccine Biological: Trivalent inactivated influenza vaccine
Two doses of 0.25 ml vaccine delivered IM at least 4 weeks apart.
Other Name: Vaxigrip Junior

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.

  Eligibility

Ages Eligible for Study:   6 Months to 23 Months
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01319955

Contacts
Contact: W. Abdullah Brooks, MD, MPH 88 02 988 1662 abrooks@icddrb.org
Contact: Alicia G Fry, MD, MPH 404 639 2680 agf1@cdc.gov

Locations
Bangladesh
ICDDR,B Recruiting
Dhaka, Bangladesh, 1000
Sponsors and Collaborators
International Centre for Diarrhoeal Disease Research, Bangladesh
Johns Hopkins University
Investigators
Principal Investigator: W. Abdullah Brooks, MD, MPH International Centre for Diarrhoeal Disease Research, Bangladesh
  More Information

Publications:
Responsible Party: International Centre for Diarrhoeal Disease Research, Bangladesh
ClinicalTrials.gov Identifier: NCT01319955     History of Changes
Other Study ID Numbers: PR-09054, 00002579
Study First Received: March 9, 2011
Last Updated: July 9, 2014
Health Authority: Bangladesh: Data Safety Monitoring Board

Keywords provided by International Centre for Diarrhoeal Disease Research, Bangladesh:
Pneumonia
Influenza
Child
Respiratory
Pathogen

Additional relevant MeSH terms:
Influenza, Human
Pneumonia
Lung Diseases
Orthomyxoviridae Infections
RNA Virus Infections
Respiratory Tract Diseases
Respiratory Tract Infections
Virus Diseases

ClinicalTrials.gov processed this record on November 24, 2014