Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12620000382976
Ethics application status
Approved
Date submitted
5/01/2020
Date registered
20/03/2020
Date last updated
11/10/2022
Date data sharing statement initially provided
20/03/2020
Type of registration
Retrospectively registered

Titles & IDs
Public title
A follow-up of the Randomized controlled trial of the Effect of intraVenous iron on Anaemia in Malawian Pregnant women (REVAMP) and their children: REVAMP Extend
Scientific title
A follow-up of the Randomized controlled trial of the Effect of intraVenous iron on Anaemia in Malawian Pregnant women (REVAMP) and their children: REVAMP Extend
Secondary ID [1] 299938 0
None
Universal Trial Number (UTN)
Trial acronym
REVAMP Extend
Linked study record
This record is a follow-up study of ACTRN12618001268235.

Health condition
Health condition(s) or problem(s) studied:
anaemia 315376 0
iron deficiency 315377 0
child development 315378 0
Child growth 315379 0
Maternal depression 315380 0
Infection 315381 0
Condition category
Condition code
Blood 313678 313678 0 0
Anaemia
Public Health 313679 313679 0 0
Other public health

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
This is a follow-up study of REVAMP (ACTRN12618001268235), in which pregnant women with Hb<10g/dL randomly assigned to the intervention group received the following:
Intravenous iron treatment: intravenous ferric carboxymaltose 1000mg (weight >50kg) or 20mg/kg (weight <50kg) given over 15min once at recruitment (Day 0).
Participants will comprise mothers enrolled in the trials and their babies. They will undergo ongoing observational follow up comprising questionnaires, physical assessment, cognitive assessments, and laboratory sample assessment (blood and/or stool) at 3, 6, 9 and 12 months post birth/ partum. EEG neurocognitive assessments in children at 6 months will be undertaken. Children will be assessed for the presence of radiological rickets at 6 and 12 months of age. We will take x-rays of wrist and knee to identify the presence of radiological rickets using standard techniques. A study radiologist will assess the x-rays and the data will be collected into the trial's REDCAP database. The use of x-rays is a safe and non-invasive method for the assessment of bones. Neurodevelopment will be assessed in children using portable low field magnetic resonance imaging technology (Hyperfine) as 12 months of age. After provision of detailed information and the opportunity to ask questions, mothers will be invited to provide written informed consent for their participation and the participation of their infant in the REVAMP-Bone and -Neuro sub-study. The first 200 mothers who provide informed consent for themselves and their infants will continue with the study visits. REVAMP-Extend participants will be invited to participate
Intervention code [1] 316718 0
Not applicable
Comparator / control treatment
This is a follow-up study of REVAMP (ACTRN12618001268235), in which pregnant women with Hb<10g/dL randomly assigned to the intervention group received the following:
Control group in the main trial: Oral iron treatment course: oral iron- 200mg ferrous sulphate (approx. 65mg elemental iron) given as tablets twice daily for 90 days (reaching a total dose of approx. 11.7g), for the remaining duration of pregnancy, whichever is shorter.

We will compare the interventional and control groups from the main study over the first 12 months post partum.
Control group
Active

Outcomes
Primary outcome [1] 322102 0
Child cognitive development measured using the Bayley Scales of Infant and Toddler Development-III (cognitive composite scores)
Timepoint [1] 322102 0
6 months of age
Secondary outcome [1] 377329 0
Language and Motor development measured using the Bayley Scales of Infant and Toddler Development-III (language and motor composite scores)
Timepoint [1] 377329 0
6 months of age
Secondary outcome [2] 377330 0
Child length-for-age z-score,
Timepoint [2] 377330 0
3, 6, 9, and 12 months of age
Secondary outcome [3] 377331 0
Child head circumference using tape measure
Timepoint [3] 377331 0
3, 6, 9, 12 months of age
Secondary outcome [4] 377332 0
Prevalence of child stunting using WHO growth standards
Timepoint [4] 377332 0
3, 6, 9, 12 months of age
Secondary outcome [5] 377333 0
Prevalence of malaria in children (measured by microscopy and filter paper for PCR)
Timepoint [5] 377333 0
3, 6, 9, 12 months of age
Secondary outcome [6] 377335 0
Child haemoglobin concentration using automated haemoglobin measurement
Timepoint [6] 377335 0
3, 6, 9, 12 months of age
Secondary outcome [7] 377336 0
Prevalence of child anaemia based on automated haemoglobin measurement (Hb<110g/L)
Timepoint [7] 377336 0
3, 6, 9, 12 months of age
Secondary outcome [8] 377337 0
Child ferritin concentration using automated biochemistry ferritin assays
Timepoint [8] 377337 0
3, 6, 9, 12 months of age
Secondary outcome [9] 377338 0
Prevalence of child iron deficiency (as defined by low ferritin concentration using automated ferritin assay)
Timepoint [9] 377338 0
3, 6, 9, 12 months of age
Secondary outcome [10] 377339 0
Maternal mental health as measured using the Depression, Anxiety and Stress Scale and the Edinburg Postpartum Depression Scale
Timepoint [10] 377339 0
1, 3, 6, 9, and 12 months postpartum
Secondary outcome [11] 377340 0
Microbiome to assess parasite load, microbiome diversity and composition.
Timepoint [11] 377340 0
4 weeks post intervention and 36 weeks gestation
Secondary outcome [12] 377341 0
Prevalence of maternal anaemia (Hb <11.0g/dl) measured by HemoCue using capillary blood
Timepoint [12] 377341 0
3, 6, 9, and 12 months postpartum
Secondary outcome [13] 377342 0
Maternal haemoglobin as measured on venous blood via automated analyser
Timepoint [13] 377342 0
3, 6, 9, and 12 months postpartum
Secondary outcome [14] 377343 0
Maternal anaemia (Hb<11g/dL) as measured on venous blood via automated analyser
Timepoint [14] 377343 0
3, 6, 9, and 12 months postpartum
Secondary outcome [15] 377344 0
Maternal iron deficiency (defined by i) ferritin<15mg/L, and ii) sTfR/Ferritin index – assay dependent cut-off)
Timepoint [15] 377344 0
3, 6, 9, and 12 months postpartum
Secondary outcome [16] 377345 0
Prevalence of maternal malaria parasitaemia based on RDT, microscopy, and filter paper for PCR
Timepoint [16] 377345 0
3, 6, 9, and 12 months postpartum
Secondary outcome [17] 377346 0
Maternal hypophosphatemia based on biochemical measurement of serum Phosphate
Timepoint [17] 377346 0
3, 6, 9, and 12 months postpartum
Secondary outcome [18] 377347 0
Maternal inflammation (elevated C-reactive protein by serum assay)
Timepoint [18] 377347 0
3, 6, 9, and 12 months postpartum
Secondary outcome [19] 377348 0
Incidence of maternal all-cause sick visits to the clinic based on visits recorded by study staff at the study clinic
Timepoint [19] 377348 0
1 to 12 months postpartum
Secondary outcome [20] 377349 0
Incidence of child all-cause sick visits to the clinic based on visits recorded by study staff at the study clinic
Timepoint [20] 377349 0
1 to 12 months of age
Secondary outcome [21] 378414 0
Child cognitive development measured by Event Related Potentials
Timepoint [21] 378414 0
6 months of age
Secondary outcome [22] 379428 0
weight-for-age z-score using digital scales
Timepoint [22] 379428 0
3, 6, 9 and 12 months of age
Secondary outcome [23] 379429 0
weight-for-height z-score using digital scales and infantometer measurement
Timepoint [23] 379429 0
3, 6, 9, 12 months of age
Secondary outcome [24] 379430 0
Prevalence of wasting measured using digital scales and infantometer
Timepoint [24] 379430 0
3, 6, 9, 12 months of age
Secondary outcome [25] 379431 0
Prevalence of underweight measured using digital scales
Timepoint [25] 379431 0
3, 6, 9, 12 months of age
Secondary outcome [26] 414645 0
Infant neurodevelopment measured by low field portable MRI technology
Timepoint [26] 414645 0
12 months of age
Secondary outcome [27] 414646 0
Prevalence of radiological Rickets in infants. We will take x-rays of wrist and knee to identify the presence of radiological Ricketts using standard techniques. A study radiologist will assess the x-rays and the data will be collected into the trial's REDCap. The use of x-rays is a safe and non-invasive method for the assessment of bones.
Timepoint [27] 414646 0
6 and 12 months of age

Eligibility
Key inclusion criteria
Participants must have participated in the main REVAMP trial, or be a child born to a participant of the parent study to be included in this substudy.
Participants meeting the following criteria were included in the parent trial (main REVAMP trial):
1. Confirmed singleton pregnancy at 13-26 weeks gestation
2. Moderate to severe anaemia not requiring an immediate blood transfusion (Hb <10g/dl)
3. Negative malaria parasitaemia
4. Resident in the study catchment area of Blantyre and Zomba district
5. Plan to deliver at a health facility
6. Written informed consent (including assent if <18 years old)
Minimum age
3 Months
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Non participation in the main REVAMP trial.

Study design
Purpose
Natural history
Duration
Longitudinal
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
A detailed statistical analysis plan describing the proposed analyses will be finalised before the trial database is locked for final analysis. Analyses will be undertaken on an intention-to-treat basis (child outcomes: all live-borns; maternal outcomes: all women randomized). Descriptive statistics will be presented for all outcomes, by treatment groups across the follow-up time points. The primary child outcome of cognitive development (based on the Bayley cognitive composite score) will be analysed using a linear regression, with the oral iron group as the reference, and incorporating clinic and treatment in the model. The primary child hypothesis will be evaluated by obtaining the estimate of the mean difference of IV iron versus oral iron and a 95% confidence interval. The secondary child and maternal outcomes will be analysed by fitting logistic or linear regression models with a model specification similar to that of the primary maternal outcome, where applicable also taking into account in the model the repeated data collection of the outcome. Missing values in all outcomes will be reported across treatment groups and follow-up time points. Multiple imputations under the missing at random assumption will be performed as a secondary analysis for handling missing data in the primary child outcome; results will be compared with the primary complete case analysis to investigate the robustness of the findings to missing data.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
15/07/2019
Date of last participant enrolment
Anticipated
12/02/2021
Actual
2/03/2021
Date of last data collection
Anticipated
11/02/2022
Actual
12/08/2022
Sample size
Target
862
Accrual to date
Final
862
Recruitment outside Australia
Country [1] 22153 0
Malawi
State/province [1] 22153 0
Blantyre, Zomba

Funding & Sponsors
Funding source category [1] 304398 0
Charities/Societies/Foundations
Name [1] 304398 0
Bill and Melinda Gates Foundation
Country [1] 304398 0
United States of America
Primary sponsor type
University
Name
University of Malawi, College of Medicine
Address
College of Medicine,
Private Bag 360,
Chichiri,
Blantyre 3
Malawi
Country
Malawi
Secondary sponsor category [1] 304671 0
None
Name [1] 304671 0
Address [1] 304671 0
Country [1] 304671 0
Other collaborator category [1] 281060 0
University
Name [1] 281060 0
Walter and Eliza Hall Institute of Medical Research
Address [1] 281060 0
1G Royal Parade
Parkville VIC 3052
Country [1] 281060 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 304835 0
College of Medicine Research and Ethics Committee COMREC
Ethics committee address [1] 304835 0
Ethics committee country [1] 304835 0
Malawi
Date submitted for ethics approval [1] 304835 0
24/05/2019
Approval date [1] 304835 0
07/07/2019
Ethics approval number [1] 304835 0
P.02/18/2357
Ethics committee name [2] 304849 0
The Walter and Eliza Hall Institute of Medical Research Human Research Ethics Committee
Ethics committee address [2] 304849 0
Ethics committee country [2] 304849 0
Australia
Date submitted for ethics approval [2] 304849 0
01/11/2019
Approval date [2] 304849 0
02/11/2019
Ethics approval number [2] 304849 0
18/02

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 98366 0
Dr Sant-Rayn Pasricha
Address 98366 0
Population Health and Immunity/ Infection and Immunity Divisions
The Walter and Eliza Hall Institute of Medical Research
1G Royal Parade
Parkville VIC 3052
Australia
Country 98366 0
Australia
Phone 98366 0
+61393452618
Fax 98366 0
Email 98366 0
[email protected]
Contact person for public queries
Name 98367 0
Sant-Rayn Pasricha
Address 98367 0
Population Health and Immunity/ Infection and Immunity Divisions
The Walter and Eliza Hall Institute of Medical Research
1G Royal Parade
Parkville VIC 3052
Australia
Country 98367 0
Australia
Phone 98367 0
+61393452618
Fax 98367 0
Email 98367 0
[email protected]
Contact person for scientific queries
Name 98368 0
Sant-Rayn Pasricha
Address 98368 0
Population Health and Immunity/ Infection and Immunity Divisions
The Walter and Eliza Hall Institute of Medical Research
1G Royal Parade
Parkville VIC 3052
Australia
Country 98368 0
Australia
Phone 98368 0
+61393452618
Fax 98368 0
Email 98368 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Individual participant data (IPD) underlying published results only
When will data be available (start and end dates)?
IPD will be available from 31st December 2025 onwards (no end date)
Available to whom?
Case by case basis at the discretion of the Principal Investigator
Available for what types of analyses?
To achieve the aims in an approved proposal, for IPD meta-analyses
How or where can data be obtained?
Access subject to approvals by Principal Investigator (email [email protected])


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
17325Study protocol  [email protected]



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
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