Non-inferiority of Lower Dose Calcium Supplementation During Pregnancy

Study Overview
=================
Brief Summary
-----------------
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.

Official Title
-----------------
Demonstrating Non-inferiority of Lower Dose Calcium Supplementation During Pregnancy for Reducing Preeclampsia and Neonatal Outcomes

Conditions
-----------------
Pregnancy Related

Intervention / Treatment
-----------------
* Dietary Supplement: Daily 500 mg elemental calcium as calcium carbonate
* Dietary Supplement: Daily1500 mg elemental calcium as calcium carbonate


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Daily 500 mg Calcium<br> | Dietary Supplement: Daily 500 mg elemental calcium as calcium carbonate<br>* 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.<br>|
| Active Comparator: Daily1500 mg Calcium (Standard dose)<br> | Dietary Supplement: Daily1500 mg elemental calcium as calcium carbonate<br>* 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.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of pregnant women with incident preeclampsia |  | Gestational week 20 to Delivery | 
| Proportion of preterm birth |  | Birth |