Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT02669654 |
| Other study ID # |
PR-14066 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
Phase 4
|
| First received |
|
| Last updated |
|
| Start date |
November 1, 2015 |
| Est. completion date |
October 31, 2021 |
Study information
| Verified date |
February 2021 |
| Source |
International Centre for Diarrhoeal Disease Research, Bangladesh |
| Contact |
Nurul Hoque Alam, MD |
| Phone |
9827001-10 |
| Email |
nhalam[@]icddrb.org |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Background: At present pneumonia and malnutrition have become the leading causes of mortality
among <5-year-old children in developing countries. World Health Organization standard
management of severe pneumonia and severe malnutrition requires hospitalization for
supportive care. As many developing countries including Bangladesh do not have enough
pediatric hospital beds to accommodate the demand for admission of all children with severe
pneumonia and malnutrition, Investigators developed alternative treatment option such as "Day
Care Approach", for those children who cannot be hospitalized, but are too sick to be managed
in the community. After successful Day Care Approach of management of efficacy trials with
severe childhood pneumonia and severe malnutrition, the next step is to conduct an
effectiveness trial under "real life" condition, i.e. within the Health Systems of
Bangladesh.
Burden: Pneumonia is the leading cause of mortality in developing countries, being
responsible for 1,368,000 (18%) of annual 7.6 million deaths, 95% occurring in developing
countries. Similarly, malnutrition is a major health problem with an estimated 1.7 & 3.6
million children dying annually because of Severe Acute Malnutrition & Moderate Acute
Malnutrition, respectively.
Objectives: To assess & implement the Day Care Approach of management of severe childhood
pneumonia with or without Moderate Acute Malnutrition and/or severe underweight into existing
Health Systems of Bangladesh as a safe & cost effective alternative to Existing Treatment.
Methods: A cluster randomized controlled trial will be conducted in Bangladesh by involving
16 clusters (Wards) in Dhaka & 16 clusters (Unions) in rural areas that will be randomly
assigned to intervention & control arm. Children with severe pneumonia will be enrolled in
(i) Tikatuli, (ii) Circular Road, (iii) Dhamrai Upazilla of Dhaka, (iv) Karimganj Upazillas
to one of two management schemes: (i) Existing Treatment in control clusters or (ii) Day care
Approach in intervention clusters by involving Comprehensive Reproductive Health Centres in
urban and Health and Family Welfare Centres in rural areas.
Outcome variables:
- Primary: clinical treatment failure by day 6
- Secondary:
(i) Treatment failure between day 7-14 in children who are well on day 6 (ii) Cost
effectiveness (iii) Referrals to hospitals (iv) Deaths
Description:
Specific Objectives:
1. To assess whether or not the Day care Approach for the management of severe childhood
pneumonia with or without moderate acute malnutrition and/or severe underweight
incorporated into the existing urban and rural Health Systems of Bangladesh is safe and
effective.
2. To implement the Day care Approach for the management of severe childhood pneumonia with
or without moderate acute malnutrition and/or underweight within the Health Systems of
Bangladesh as a cost effective alternative to the Existing Treatment of care for both
the Health Systems and the families.
3. To examine and compare the cost effectiveness of the Day care Approach versus Existing
Treatment of care for the management of severe childhood pneumonia with or without
moderate acute malnutrition and/or severe underweight.
4. To identify and assess potential barriers and challenges during the whole implementation
process.
Background of the Project including Preliminary Observations:
At present and depending on clinical presentation, pneumonia is classified as severe
pneumonia, pneumonia, or no pneumonia, according to the recent guidelines by the World Health
Organization in 2013. Since pneumonia is the leading cause of death in <5-year-old children,
interventions to promote the prevention and treatment of pneumonia are an essential part of
child survival efforts to achieve Millennium Development Goal 4. World Health Organization
standard management of severe pneumonia requires hospitalization for supportive treatment
including oxygen therapy for hypoxaemia, airway suctioning, fluid and nutritional management,
antibiotics, and careful monitoring.
Most, if not all, developing countries including Bangladesh do not have enough hospitals, or
pediatric hospital beds to accommodate the demand for admission of all children with severe
pneumonia with or without malnutrition and other co-morbidity. In addition, mothers of ill
children have other childcare and household responsibilities that constrain their ability to
attend the child during hospitalization, which is often mandatory. Furthermore,
transportation, cost, long distance from the hospital, lack of adequate child-care at home,
or cultural perceptions represent additional huge limitations to hospitalization.
Hospitalization also may not be feasible due to inability of parents to stay in hospital for
the entire duration of illness. The sum total of all these common potential constraints lead
to failure of hospitalization of children with severe pneumonia and severe malnutrition with
or without additional co-morbidity. This inadequate availability and use of hospital beds
leading to failure of hospitalization of children with severe pneumonia and/or malnutrition
assuredly results in excess and unwanted deaths of children, who, with proper care, would
otherwise survive. Although Investigators do not have direct evidence (no data available)
that the bottleneck to pneumonia deaths in Bangladesh is lack of hospital beds mainly. But
Investigators know from experience that many children with severe pneumonia requiring
hospitalization are not hospitalized due to the lack of free pediatric beds, as observed
during the observational day care studies.
Study Design A cluster randomized controlled clinical trial will be conducted in urban Dhaka
and rural Bangladesh. The trial areas are pre-selected on the basis of infrastructure
(adequate space, water supply, electricity, and willingness for performing the study). In the
urban areas, 16 clusters equivalent to Wards (either whole or partial), with a population of
50,000 to 80,000 each and in the rural areas, another 16 clusters equivalent to Unions each
with about 20,000 to 30,000 inhabitants. Children with severe pneumonia, according to recent
World Health Organization criteria (2013) with or without malnutrition will be enrolled into
the study in urban Dhaka: (i) Tikatuli, Surjer Hashi Clinic, 12, K.M. Das Lane and (ii)
Circular Road Circular Road Surjer Hashi Clinic, New Circular Road; and rural Bangladesh:
(iii) Dhamrai Upazilla of Dhaka District, and (iv) Karimganj Upazilla of Kishoreganj District
to one of the two management schemes: (i) the Existing Treatment in the control clusters, or
(ii) the Day care Approach in the intervention clusters. Children with history of cough,
fever and difficult breathing suggestive of having severe pneumonia will be enrolled at
primary health facilities such as Primary Health Care Centres or Comprehensive Reproductive
Health Centres in the urban areas and Health and Family Welfare Centres or Community Clinics
in the rural areas.
Methods
Primary study sites Urban: United States Agency for International Development -Department For
International Development support Non Government Organization Health Service Delivery Project
through Pathfinder run by the Population Services and Training Center and Concerned Women for
Family Development. The Ministry of Health and Family Welfare contributes to urban health
care through the outpatient services offered through its secondary, tertiary and specialized
hospitals located in the urban settings.
Rural: Health services in Bangladesh in the rural areas are mostly provided by the
Government's Ministry of Health and Family Welfare, Non-Government Organizations (NGOs), and
private providers. In the government sector, two community based workers - a family welfare
assistant and a health assistant - and a community clinic run by a community health care
provider serve a population of 6000 to 7000. Another first level outpatient clinic - e.g.
Union Health and Family Welfare Centres - serves a population of about 20,000.
Randomization and masking The trial field sites have been pre-selected on the basis of
infrastructure (adequate space, water supply, electricity and willingness for performing the
study).
Case Management
Existing Treatment (control) clusters
Children in the control Existing Treatment clusters with pneumonia (not severe pneumonia)
with/without malnutrition will be identified by the Community Health Worker/Community Service
Providers in the urban areas or Field Research Assistants/Field Assistants in the rural
areas, or self-referred by the parents/caregivers to the Primary Health Care Centres (Vital
clinics)/Comprehensive Reproductive Health Centres (Ultra clinics) in the urban areas and
Community Clinics/Health and Family Welfare Centres in the rural areas.
Follow-up in the Existing Treatment control clusters
Community Health Workers/Field Research Assistants/Field Assistants will perform the
follow-up visits at the clinics on days 2, child's home on day 3, and clinics on day 6 and
day 14 (window period + 1 day) in the Existing Treatment clusters of all four primary study
sites.
In case of treatment failure in control areas children will be referred to hospital from Day
2.
Day Care Approach (Intervention) clusters
Similarly, children of the intervention Day care Approach clusters with pneumonia (not severe
pneumonia) with or without malnutrition will be addressed in the same manner as the control
clusters, i.e. be identified by the Community Health Workers in the urban areas and Field
Research Assistants/Field Assistants in the rural areas. As with the children in the control
clusters at the 1st level care centres (Primary Health Care Centres/Comprehensive
Reproductive Health Centres in the urban areas and Community Clinics/Health and Family
Welfare Centres in the rural areas), the children will be assessed by the
Physicians/Pediatricians working at the Comprehensive Reproductive Health Centres in the
urban areas and by the Sub Assistant Community Medical Officers working at the Health and
Family Welfare Centres in the rural areas and finally evaluated by a trained study physician
and treated at home with oral antibiotics (syrup Amoxicillin 90 mg/kg three divided doses or
Co-trimoxazole 40 mg/kg two divided doses per day for 5 days).
Children with pneumonia (i.e., not severe pneumonia) who fail to the community level oral
Amoxicillin/Co-trimoxazole treatment for two days as well as those presenting with severe
pneumonia (self-referred or identified by Community Health Workers/Field Research
Assistants/Field Assistants) right from beginning will be assessed by the
Physicians/Pediatricians working at the Comprehensive Reproductive Health Centres in the
urban areas and by the Sub Assistant Community Medical Officers working at the Health and
Family Welfare Centres in the rural areas and finally evaluated by a trained study physician
and directly referred to the Comprehensive Reproductive Health Centres in the urban areas or
Health and Family Welfare Centres in the rural areas for Day care Approach of management. For
this purpose, the children will be admitted to a day-care section of the Comprehensive
Reproductive Health Centres in the urban areas from 08:30 to 17:00 hours and to a day-care
section of the Health and Family Welfare Centres in the rural areas from 08:30 to 15:00 hours
on all days of the week including weekends and public holidays, until fulfilling the criteria
for discharge (clinical end-points, defined as no hypoxemia, no fever, no fast breathing and
no tachycardia). Parents will bring their children to the Comprehensive Reproductive Health
Centres/Health and Family Welfare Centres at 8:30 hours in the morning every day and return
them back home at 15:00 hours in rural areas or 17:00 hours in urban areas.
Follow-up study up to 3 months after discharge
After successful management of all enrolled study children belonging to all Existing
Treatment/Day care Approach clusters will be discharged from the Comprehensive Reproductive
Health Centres/Health and Family Welfare Centres. The study physicians will inform the
parents on the dates of follow-up visits for the next 3 months written down in the discharge
certificate.
Economic Evaluation of Intervention Alternatives
Effectiveness trial of severe pneumonia without/with Moderate Acute Malnutrition and or
severe underweight is planned to implement the Day care Approach of treatment into the urban
Comprehensive Reproductive Health Centres in Dhaka city or the rural Health and Family
Welfare Centres of Bangladesh.
Cost of intervention
Intervention costs consist of the costs of providers and households.
Cost of provider Cost to household
Sample Size Calculation and Outcome (Primary and Secondary) Variable(s)
Cluster-randomized design for dichotomous outcomes with an equivalency design and the
explicit expectation that the results on primary outcomes would fall within the 95%
Confidence Intervals. Because the number of clusters is fixed at 8 clusters per site per year
including 4 control and 4 intervention and a power of 90%, coefficient of variation of 0.20,
and an alpha of 0.05. On the basis of these assumptions, 50 children with severe pneumonia
with or without malnutrition with or without severe under-weight per cluster per year will be
enrolled over 2.5 years, for an estimated 2000 patients in each study arm including 15%
drop-outs. 32 clusters will be needed in each study arm. Therefore, for a period of 2.5
years, a total of 4000 children can be easily recruited within the time frame from 4 primary
study sites. The estimated incidence of pneumonia is taken as 0.23 episode/ child/ year.
Outcome Variables
- The primary outcome variable will be the following (i) Clinical treatment failure by day
6 after enrollment (ii) Success rate of the Health System Day acre Approach plus
referral to hospital verses Existing Treatment plus referral to hospital)
- The secondary outcome variables will be:
(iii) Treatment failure or relapse between day 7 and day 14 in children who are well on day 6
(iv) Economic evaluation (cost-effective analyses) (v) Referrals to hospitals (vi) Deaths
(vii) Compliance to treatment (viii) Anthropometrical indices such as body weight,
length/height, Mid Upper Arm Circumference, Weight-for-Age (%), Weight-for-Height (%),
Height-for-Age (%) (ix) Morbidity, mortality, relapse and hospitalization during 3-months
follow-up after discharge from the study (x) Family/patient satisfaction
