Trial Review

Please note that the ANZCTR website will be unavailable from 1:00pm until 2:30pm (AEST) on Thursday 5th June for website maintenance.
Please be sure to log out of the system in order to avoid any loss of data. Thank you and apologies for any inconvenience caused.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12625000532404
Ethics application status
Approved
Date submitted
5/02/2025
Date registered
27/05/2025
Date last updated
27/05/2025
Date data sharing statement initially provided
27/05/2025
Type of registration
Prospectively registered

Titles & IDs
Public title
Evaluation of blood phosphate levels following intravenous iron treatment of anaemic pregnant women in their second trimester in Bangladesh
Scientific title
Evaluation of serum phosphate following intravenous iron (ferric carboxymaltose) treatment of anaemic pregnant women in their second trimester in Bangladesh
Secondary ID [1] 313890 0
None
Universal Trial Number (UTN)
Trial acronym
EDIVA Phase
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Anemia 336567 0
Iron deficiency 336568 0
Hypophosphatemia 336569 0
Condition category
Condition code
Blood 333077 333077 0 0
Anaemia
Reproductive Health and Childbirth 333078 333078 0 0
Fetal medicine and complications of pregnancy

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants will be assigned to receive the following once during the second trimester: intravenous ferric carboxymaltose (1000 mg for body weight >50 kg, or 20 mg/kg for body weight <50 kg) in 250mL normal saline, over 15 minutes. The intervention is administered by a nurse at a health facility and it is recorded in the trial database as a condition of being enrolled in the trial. Therefore, the administration of the intervention will be directly observed.
Intervention code [1] 330476 0
Treatment: Drugs
Comparator / control treatment
This is a single arm interventional study with no control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 340617 0
The mean nadir serum phosphate concentration following a single treatment dose of FCM to treat anaemia in pregnant women.
Timepoint [1] 340617 0
The lowest serum phosphate concentration will be determined from sampling at 12 time points following the administration of ferric carboxymaltose. The time points are 3 days, 7 days, 10 days, 14 days, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 8 weeks, 10 weeks post-intervention, and 34 weeks’ gestation.
Secondary outcome [1] 444604 0
The timecourse of changes in serum phosphate over the study period.
Timepoint [1] 444604 0
Serum phosphate will be measured at 3 days, 7 days, 10 days, 14 days, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 8 weeks and 10 weeks post-intervention, and at 34 weeks’ gestation.
Secondary outcome [2] 444609 0
Timecourse of the effect of a single dose of ferric carboxymaltose on haemoglobin concentrations over the study period.
Timepoint [2] 444609 0
Haemoglobin will be measured from blood samples obtained at 3 days, 7 days, 10 days, 14 days, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 8 weeks and 10 weeks post-intervention, as well as 34 weeks’ gestation.
Secondary outcome [3] 444610 0
The effect of a single dose of ferric carboxymaltose on bone turnover as measured by bone turnover markers in the blood.
Timepoint [3] 444610 0
The time points are baseline (recruitment), 3 days, 7 days, 10 days, 14 days, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 8 weeks, 10 weeks post-intervention, as well as 34 weeks’ gestation.
Secondary outcome [4] 444611 0
Timecourse of the effect of a single dose of ferric carboxymaltose on bone metabolic parameters (calcium) over the study period.
Timepoint [4] 444611 0
The time points are baseline (recruitment), 3 days, 7 days, 10 days, 14 days, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 8 weeks, 10 weeks post-intervention, as well as 34 weeks’ gestation.
Secondary outcome [5] 444613 0
Proportion of women with at least one treatment related adverse effect (occurring immediately post-infusion)
Timepoint [5] 444613 0
The timepoint is the recruitment visit.
Secondary outcome [6] 444614 0
Proportion of women with symptoms of clinical hypophosphatemia at each study visit.
Timepoint [6] 444614 0
The timepoints are recruitment, 3 days, 7 days, 10 days, 14 days, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 8 weeks and 10 weeks post-intervention, as well as 34 weeks’ gestation and delivery.
Secondary outcome [7] 445069 0
Timecourse of the effect of a single dose of ferric carboxymaltose on iron parameters (ferritin) over the study period.
Timepoint [7] 445069 0
Ferritin will be measured from serum samples obtained at 3 days, 7 days, 10 days, 14 days, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 8 weeks and 10 weeks post-intervention, as well as at 34 weeks’ gestation

Eligibility
Key inclusion criteria
Participants meeting the following criteria will be included in the trial:
1. Confirmed singleton pregnancy in the second trimester (13-25 completed weeks of gestation), dated by ultrasound.
2. Moderate to severe anaemia (capillary haemoglobin (Hb) <10g/dl).
3. Currently afebrile.
4. Expected to deliver the baby inside or within 30 minutes of road transport of the study catchment area.
5. Have drinking water iron <2mg/L.
5. Written informed consent (if <18 years of age, consent will be collected from her guardian, while she will sign an assent form).
Minimum age
13 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Previous enrolment in EDIVA trial (PR-20125).
2. Actively participating in another intervention trial.
3. Known hypersensitivity to the study drug.
4. Clinical symptoms of current bacterial/ viral infection (fever, focal symptoms of internal infection i.e. LRTI/ diarrhoea).
5. Any condition requiring hospitalisation in the next seven days or serious concomitant illness.
6. Known to have a diagnosis of thalassemia, sickle cell or sickle-haemoglobin C anaemia or other inherited red cell condition
7. Women with severe anaemia requiring an emergency blood transfusion (Hb <5g/dL), or with haemodynamic or acute clinical compromise as judged by a study physician.
8. Known diagnosis of preeclampsia
9. Known diagnosis of X-linked hypophosphatemia
10. Women who have already received a dose of intravenous iron during the current pregnancy.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 4
Type of endpoint/s
Safety
Statistical methods / analysis
We plan to recruit 55 women in total. A sample size of 44 participants with complete data at nadir will have 90% power to demonstrate that the nadir of phosphate is statistically significantly higher than the threshold of moderate hypophosphatemia (i.e. > 2 mg/dL), assuming a mean phosphate of 2.5 mg/dL with standard deviation of 1 mg/dL [Rosano, 2020] and two-sided 5% level of significance using a one-sample t-test. In addition, this sample size will allow estimating the mean phosphate at nadir with a precision of +/-0.3 mg/dL (i.e. two-sided 95% confidence interval 2.2 to 2.8 mg/dL) if the sample mean and standard deviation are equal to our assumptions. Using a conservative assumption of 20% drop-out due to the burden of involvement in this study, 55 women are required to be enrolled.

A detailed statistical analysis plan for the final analysis will be drawn up during the course of the study and finalised before the start of data analysis. Serum phosphate, maternal haemoglobin, iron parameters, key bone metabolic parameters (e.g. calcium), and bone turnover markers in the blood (e.g., alkaline phosphatase, ALP), will be analysed using mixed effects regression models to describe longitudinal changes following a single dose of intravenous iron over the study period. Appropriate transformation of the outcome may be applied before fitting the statistical model. Safety including adverse events (occurring immediately post-infusion) and hypophosphatemia (clinical and biochemical) at baseline and during the study period will be summarised.

Reference:
Rosano G. A pooled analysis of serum phosphate measuremens and potential hypophosphatemia events in 45 interventional trials with ferric carboxymaltose. J Clin Med 2020; 9:3587-600.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
6/06/2025
Actual
Date of last participant enrolment
Anticipated
27/02/2026
Actual
Date of last data collection
Anticipated
30/06/2026
Actual
Sample size
Target
55
Accrual to date
Final
Recruitment outside Australia
Country [1] 26863 0
Bangladesh
State/province [1] 26863 0

Funding & Sponsors
Funding source category [1] 318358 0
Charities/Societies/Foundations
Name [1] 318358 0
Bill and Melinda Gates Foundation
Country [1] 318358 0
United States of America
Primary sponsor type
Other
Name
icddr,b
Address
Country
Bangladesh
Secondary sponsor category [1] 320760 0
Other
Name [1] 320760 0
The Walter and Eliza Hall Institute of Medical Research
Address [1] 320760 0
Country [1] 320760 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 316989 0
Ethical Review Committee, IRB Secretariat, Research Administration, CMS International Centre for Diarrhoeal Disease Research, Bangladesh
Ethics committee address [1] 316989 0
Ethics committee country [1] 316989 0
Bangladesh
Date submitted for ethics approval [1] 316989 0
Approval date [1] 316989 0
03/07/2024
Ethics approval number [1] 316989 0
PR-24032
Ethics committee name [2] 316990 0
The Walter and Eliza Hall Institute of Medical Research's Human Research Ethics Committee
Ethics committee address [2] 316990 0
Ethics committee country [2] 316990 0
Australia
Date submitted for ethics approval [2] 316990 0
01/10/2024
Approval date [2] 316990 0
01/10/2024
Ethics approval number [2] 316990 0

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

Contacts
Principal investigator
Name 139674 0
Prof Sant-Rayn Pasricha
Address 139674 0
Infection and Global Health Division, Walter and Eliza Hall Institute, 1G Royal Parade, Parkville, Victoria 3052
Country 139674 0
Australia
Phone 139674 0
+61 393452618
Fax 139674 0
Email 139674 0
[email protected]
Contact person for public queries
Name 139675 0
Sant-Rayn Pasricha
Address 139675 0
Infection and Global Health Division, Walter and Eliza Hall Institute, 1G Royal Parade, Parkville, Victoria 3052
Country 139675 0
Australia
Phone 139675 0
+61 393452618
Fax 139675 0
Email 139675 0
[email protected]
Contact person for scientific queries
Name 139676 0
Sant-Rayn Pasricha
Address 139676 0
Infection and Global Health Division, Walter and Eliza Hall Institute, 1G Royal Parade, Parkville, Victoria 3052
Country 139676 0
Australia
Phone 139676 0
+61 393452618
Fax 139676 0
Email 139676 0
[email protected]

Data sharing statement
Will the study consider sharing individual participant data?
Yes
Will there be any conditions when requesting access to individual participant data?
Persons/groups eligible to request access:
• This will be determined on a case-by-case basis at the discretion of Principal Investigator

Conditions for requesting access:
• -

What individual participant data might be shared?
• Individual participant data underlying published results only

What types of analyses could be done with individual participant data?
• To achieve the aims in an approved proposal, for IPD meta-analyses

When can requests for individual participant data be made (start and end dates)?
From:
IPD available from 31st December 2026 onwards (no end date)

To:
-

Where can requests to access individual participant data be made, or data be obtained directly?
• Access subject to approvals by Principal Investigator (email [email protected])

Are there extra considerations when requesting access to individual participant data?
No


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
24511Study protocol  [email protected] Will be made available at the time of datasharing.... [More Details]



Results publications and other study-related documents

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

Documents added automatically
No additional documents have been identified.