Non-inferiority of Lower Dose Calcium Supplementation During Pregnancy
Demonstrating Non-inferiority of Lower Dose Calcium Supplementation During Pregnancy for Reducing Preeclampsia and Neonatal Outcomes
The World Health Organization currently recommends that pregnant women in populations with low calcium intake receive daily calcium supplementation (1500 - 2000 mg) divided into three doses which are preferably taken at mealtimes, in addition to daily iron folic-acid supplements. Despite proven efficacy and the WHO recommendation, calcium supplementation in pregnancy is not standard of care in the vast majority of low-income and middle-income countries. Two important barriers to implementation are the cost of the supplements and complexity of the suggested calcium dosing schedule. A lower dose of calcium (500 mg) administered as a single dose has been shown to be beneficial in several trials, and if found to be as effective as the 1500 mg supplementation regimen, it may help overcome these barriers and increase individual and health system adoption.
The Investigators will conduct two parallel, individually randomized, double blind non-inferiority trials in India and Tanzania. Participating pregnant woman will be randomized to either 1500 mg or 500 mg calcium supplementation. The India and Tanzania trials are independently powered for the primary outcomes of i) preeclampsia and ii) preterm birth. The India and Tanzania sites will each enroll 11,000 participants.
Study Overview
Status
Conditions
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Nulliparous
- Attending first ANC visit at study clinics
- Pregnant women <20 weeks
- ≥ 18 years old
- Intending to stay in study area until 6 weeks post delivery
- Provides informed consent
Exclusion Criteria:
- History or signs and/or symptoms of nephrolithiasis
- Prior diagnosis of parathyroid disorder or thyroidectomy
- Diseases that require digoxin, phenytoin, or tetracycline therapy
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Experimental: Daily 500 mg Calcium
|
Pregnant women in this arm will be provided and counselled to take three tablets, one containing 500 mg elemental calcium as calcium carbonate and 2 placebo supplements daily (total of 500 mg daily).
The supplements in India will also contain 83.3 IU each of vitamin D3, for a total of 250 IU daily.
No vitamin D3 will be given in Tanzania.
|
|
Active Comparator: Daily1500 mg Calcium (Standard dose)
|
Pregnant women in this arm will be provided and counselled to take three tablets each containing 500 mg elemental calcium as calcium carbonate daily (total of 1500 mg daily) as currently recommended by the World Health Organization.
The supplements in India will also contain 83.3 IU each of vitamin D3, for a total of 250 IU daily.
No vitamin D3 will be given in Tanzania.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
|---|---|
|
Proportion of pregnant women with incident preeclampsia
Time Frame: Gestational week 20 to Delivery
|
Gestational week 20 to Delivery
|
|
Proportion of preterm birth
Time Frame: Birth
|
Birth
|
Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Wafaie W Fawzi, MBBS, DrPH, Harvard School of Public Health (HSPH)
Publications and helpful links
General Publications
- Dwarkanath P, Muhihi A, Sudfeld CR, Rani S, Duggan CP, Sando MM, Wylie BJ, Fernandez R, Kinyogoli S, Munk C, Perumal N, Raj JM, Buggi N, Swai N, Thomas T, Wang M, Kurpad AV, Masanja H, Pembe AB, Fawzi WW. Non-inferiority of low-dose compared to standard high-dose calcium supplementation in pregnancy: study protocol for two randomized, parallel group, non-inferiority trials in India and Tanzania. Trials. 2021 Nov 24;22(1):838. doi: 10.1186/s13063-021-05811-7.
- Dwarkanath P, Muhihi A, Sudfeld CR, Wylie BJ, Wang M, Perumal N, Thomas T, Kinyogoli SM, Bakari M, Fernandez R, Raj JM, Swai NO, Buggi N, Shobha R, Sando MM, Duggan CP, Masanja HM, Kurpad AV, Pembe AB, Fawzi WW. Two Randomized Trials of Low-Dose Calcium Supplementation in Pregnancy. N Engl J Med. 2024 Jan 11;390(2):143-153. doi: 10.1056/NEJMoa2307212.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- OPP1172660
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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