Clinical trial NCT01319955: Flu Vaccine Against Childhood Pneumonia, Bangladesh
Official title: Influenza Vaccine Efficacy Against Childhood Pneumonia in an Urban Tropical Setting
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pneumonia
Laboratory Confirmed Influenza
Keywords: Pneumonia
Influenza
Child
Respiratory
Pathogen
Lead sponsor: International Centre for Diarrhoeal Disease Research, Bangladesh
Sponsor class: OTHER
Collaborators: name: Johns Hopkins University
name: Centers for Disease Control and Prevention
First posted: 2011-03-22
Enrollment: 3508
Sex: ALL
Minimum age (years): 6
Maximum age (years): 23
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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. 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.

Eligibility 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.

Primary outcomes:
measure: Clinical pneumonia
timeFrame: Up to 12 months post-vaccination
measure: Laboratory confirmed influenza infection
timeFrame: Up to 12 months post-vaccination
Secondary outcomes:
measure: Indirect effects
timeFrame: Up to 12 months post-vaccination
measure: Epidemiological and clinical characteristics of influenza infection
timeFrame: Up to 12 months post vaccination
measure: Effect on non-influenza viral and bacterial invasive disease
timeFrame: Up to 12 months post vaccination
measure: Immunogenicity
timeFrame: Within 4 months of vaccine administration
measure: Adverse events associated with the vaccine
timeFrame: Beginning Day 0 (day of vaccination) and for the next 7 days
Other outcomes:
Locations:
city: Dhaka
country: Bangladesh
facility: ICDDR,B
Study officials:
affiliation: International Centre for Diarrhoeal Disease Research, Bangladesh
name: W. Abdullah Brooks, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: Rolfes 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.