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Trial registered on ANZCTR


Trial ID
ACTRN12612000588897
Ethics application status
Approved
Date submitted
30/05/2012
Date registered
31/05/2012
Date last updated
13/09/2013
Type of registration
Prospectively registered

Titles & IDs
Public title
A trial to evaluate the impact of an early start to iron/folic acid supplementation in pregnancy on deaths of newborns in rural Bangladesh
Scientific title
A community-based cluster randomized controlled trial in rural Bangladesh to evaluate the impact of the use of iron/folic acid supplements early in pregnancy on the risk of neonatal mortality
Secondary ID [1] 280190 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Neonatal mortality 286125 0
Preterm delivery 286126 0
Iron deficiency 286133 0
Low birthweight 286134 0
Condition category
Condition code
Public Health 286316 286316 0 0
Epidemiology
Reproductive Health and Childbirth 286317 286317 0 0
Antenatal care

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
In the intervention clusters trained BRAC (Bangladesh Rural Advancement Committee, an NGO based in Bangladesh) village volunteers will identify pregnant women and provide consenting women with a daily dose of iron (60 mg)/folic acid (400ug) supplementation early in pregnancy (in the first trimester) to be taken orally and sustained for at least 180 days, ensure resupply of supplements through fortnightly visits, and provide counselling in support of early uptake, continued use of the supplements until delivery, and compliance with the supplementation regime. This intervention is consistent with the Bangladesh Ministry of Health guidelines.

To achieve early contact with the women in pregnancy the BRAC village volunteers will identify pregnant women through routine surveillance visits to the households in their area every month.

In all clusters the BRAC village field workers will identify the pregnancy outcomes, the deaths of the neonates and mothers, and inform the study assistants who will make a visit and confirm these events and collect other details. Both intervention and control treatment arms will receive the usual antenatal and postnatal care services provided by the Bangladesh Ministry of Health, which are supported by the BRAC Essential Health Care program.
Intervention code [1] 284515 0
Prevention
Comparator / control treatment
Standard treatment: the usual antenatal and postnatal care services provided by the Bangladesh Ministry of Health, which are supported by BRAC Essential Health Care Program.
Control group
Active

Outcomes
Primary outcome [1] 286798 0
All infant deaths occurring in the first month of life assessed by the data collected by the trained research field worker visits.
Timepoint [1] 286798 0
Four weeks and 6 weeks after dlivery.
Secondary outcome [1] 296669 0
Percentage of women using iron/folic acid as prescribed in the first trimester of pregnancy assessed by data collected by trained research field worker visits.
Timepoint [1] 296669 0
In large scale cohort follow up of pregnant women registered in the trial during the first, 2nd and 3rd trimester of pregnancy.
Secondary outcome [2] 296670 0
Percentage of live births with low birthweight (weighing <2500g) (intensive).
Timepoint [2] 296670 0
Within 24 hours of delivery throughout the intervention.
Secondary outcome [3] 296671 0
Percentage of live births with preterm delivery (intensive). Preterm delivery is defined as a birth occurring with gestational age before 37 weeks of gestation and includes early preterm delivery (<34 weeks) based on maternal report of the date of last menstrual period (LMP).
Timepoint [3] 296671 0
Within 24 hours of delivery throughout the intervention.
Secondary outcome [4] 296672 0
Percentage of neonatal deaths attributable to preterm delivery asphyxia.
Timepoint [4] 296672 0
Within 1 month of all neonatal deaths.
Secondary outcome [5] 296673 0
Percentage of neonatal deaths attributable to preterm delivery.
Timepoint [5] 296673 0
Within 1 month of all neonatal deaths.
Secondary outcome [6] 296674 0
Mean marginal additional expenditure associated with early iron/folic acid supplementation, and the mean cost per neonatal death prevented referring to health service costs.
Timepoint [6] 296674 0
Interviews with mothers at baseline, and at follow up interviews at 4th, 6th & 8th months of pregnancy, and immediately after dlivery and 1st week & 6th week of delivery.

Eligibility
Key inclusion criteria
All pregnant women registered in the study clusters.
Minimum age
No limit
Maximum age
No limit
Gender
Females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1) Clusters on the sampling frame will be excluded if there are other interventions to improve antenatal iron/folic acid distribution currently being implemented either by government or non-government sectors. 2) Clusters located in areas where access is extremely difficult, for example, low land areas which are prone to flooding for extended periods of the year, will also be excluded.
3) Cohort evaluation: Pregnant women with more than 16 weeks of gestational age at enrollment will be excluded from ‘cohort’ follow-up.

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Trained field assstants (in this study trained BRAC village field workers) will identify women who have recently become pregnant by systematic door-to-door surveys across around 200 households in their area over a 2 month period. Any pregnant women resident in the cluster will be included.
Allocation is not concealed.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The interventions will be assigned to eligible clusters using a fixed randomization scheme with uniform allocation ratio of treatments, stratified by Sub-Districts (upazilla) and in blocks of 5 or 10 to ensure geographic balance across each geographic area. The random allocation sequence will be generated using SAS software. The nature of the intervention precludes the masking of the treatments.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment outside Australia
Country [1] 4211 0
Bangladesh
State/province [1] 4211 0
Dhaka Division

Funding & Sponsors
Funding source category [1] 284946 0
Government body
Name [1] 284946 0
National Health & Medical Research Council of Australia
Address [1] 284946 0
Level 1, 16 Marcus Clarke Street
Canberra ACT 2601
Country [1] 284946 0
Australia
Primary sponsor type
University
Name
The University of Sydney
Address
NSW 2006
Country
Australia
Secondary sponsor category [1] 283820 0
Other
Name [1] 283820 0
International Centre for Diarrhoeal Disease Research, Bangladesh
Address [1] 283820 0
Mohakhali, Dhaka 1212
Country [1] 283820 0
Bangladesh
Other collaborator category [1] 260652 0
Other
Name [1] 260652 0
Bangladesh Rural Advancement Committee (BRAC)
Address [1] 260652 0
75 Mohakhalia, Dhaka 1212
Country [1] 260652 0
Bangladesh

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 286960 0
Ethical Review Committee of the International Centre for Diarrhoeal Disease Research, Bangladesh
Ethics committee address [1] 286960 0
Mohakhali, Dhaka 1212
Ethics committee country [1] 286960 0
Bangladesh
Date submitted for ethics approval [1] 286960 0
20/02/2012
Approval date [1] 286960 0
Ethics approval number [1] 286960 0
PR-11074
Ethics committee name [2] 289885 0
The University of Sydney Human Research Ethics Committee
Ethics committee address [2] 289885 0
Level 6, Jane Foss Russell Building - G02
City Road, Darlington Campus
University of Sydney, NSW 2006
Ethics committee country [2] 289885 0
Australia
Date submitted for ethics approval [2] 289885 0
Approval date [2] 289885 0
26/09/2012
Ethics approval number [2] 289885 0
14915

Summary
Brief summary
BACKGROUND
In rural Bangladesh neonatal mortality remains unacceptably high, and the current rate of decline will be insufficient for the country to reach its child survival Millennium Development Goal (MDG). An effective program of antenatal iron/folic acid supplementation in pregnant women in Bangladesh may be a key intervention to help accelerate the needed decline in neonatal mortality.

AIMS
The study aims to collect high-level evidence of whether enhanced distribution of iron-folic acid to women early in pregnancy in rural Bangladesh can improve perinatal outcomes for the infant. Specifically, the aims of the trial are to evaluate if iron-folic acid supplementation starting in the first trimester of pregnancy and sustained throughout pregnancy:
i) Reduces neonatal mortality including deaths related to preterm delivery and birth asphyxia?
ii) Reduces rates of low birth weight and preterm delivery?
iii) Is cost effective compared to the usual supplementation program?

PRIMARY HYPOTHESIS
In a cluster randomized controlled trial (CRCT) of women from rural Bangladesh, daily iron (60mg)/folic acid (400µg) starting in the 1st trimester of pregnancy, & sustained for at least 180 days, will reduce neonatal mortality by 30% from 33/1000 to 23.2/1000 live births compared to usual supplementation programs.

RESEARCH PLAN
The trial will be conducted in 4 districts (depending upon availability of sufficient BRAC field workers), where BRAC, Bangladesh’s largest NGO, currently has community programs. A CRCT will be used, in which BRAC field worker areas (SK), will be randomly allocated to an enhanced iron/folic acid, or to usual programs. In total 202 clusters will be randomized, with equal numbers per treatment group, giving a sample of 20,000 live births in 30 months. In intervention areas trained field workers will identify pregnant women & provide iron/folic acid in the 1st trimester, resupply supplements fortnightly, & provide counselling for early and continued use of supplements until delivery.

The primary outcome will be changes in the neonatal mortality rate in the intervention & comparison areas in a large scale cohort follow up of women registered in the trial using direct records of neonatal deaths. Secondary outcomes will include the percentage of women using iron/folic acid in the 1st trimester, the rates of low birth weight & preterm delivery, percentage of neonatal deaths attributable to preterm delivery & birth asphyxia. These outcomes will be assessed in an intensively followed up cohort of women followed during pregnancy until 6 weeks after birth.

OUTCOME AND SIGNIFICANCE
This project will determine if antenatal iron-folic acid from early in pregnancy will reduce neonatal deaths, & if this approach is cost-effective. This intervention potentially offers a new way to accelerate reductions in neonatal deaths that could save millions of lives.
Trial website
None
Trial related presentations / publications
None yet
Public notes

Contacts
Principal investigator
Name 33957 0
A/Prof Michael J Dibley
Address 33957 0
Sydney School of Public Health
Room: 307A, Edward Ford Building (A27)
University of Sydney, NSW 2006
Country 33957 0
Australia
Phone 33957 0
+61 2 93513620
Fax 33957 0
+61 2 9351 5049
Email 33957 0
michael.dibley@sydney.edu.au
Contact person for public queries
Name 17204 0
Dr Dr Tanvir Huda
Address 17204 0
CHNRI Secretariat Coordinator, Centre for Child and Adolescent Health, ICDDR,B; Mohakhali, Dhaka 1212
Country 17204 0
Bangladesh
Phone 17204 0
+880 2 9840523-32/Ext. 3820
Fax 17204 0
Email 17204 0
thuda@icddrb.org
Contact person for scientific queries
Name 8132 0
A/Prof A/Prof Michael Dibley
Address 8132 0
Sydney School of Public Health, Room: 307A, Edward Ford Building (A27), University of Sydney, NSW 2006
Country 8132 0
Australia
Phone 8132 0
+61 2 9351 3620
Fax 8132 0
+61 2 9351 5049
Email 8132 0
michael.dibley@sydney.edu.au