Clinical trial NCT03350516: Non-inferiority of Lower Dose Calcium Supplementation During Pregnancy
Official title: Demonstrating Non-inferiority of Lower Dose Calcium Supplementation During Pregnancy for Reducing Preeclampsia and Neonatal Outcomes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pregnancy Related
Lead sponsor: Harvard School of Public Health (HSPH)
Sponsor class: OTHER
Collaborators: name: St. John's Research Institute
name: Ifakara Health Institute
name: Africa Academy for Public Health
First posted: 2017-11-22
Enrollment: 22000
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


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

Primary outcomes:
measure: Proportion of pregnant women with incident preeclampsia
timeFrame: Gestational week 20 to Delivery
measure: Proportion of preterm birth
timeFrame: Birth
Secondary outcomes:
Other outcomes:
Locations:
city: Bangalore
country: India
facility: St. John's Research Institute
city: Dar Es Salaam
country: Tanzania
facility: Africa Academy for Public Health
city: Dar Es Salaam
country: Tanzania
facility: Ifakara Health Institute
Study officials:
affiliation: Harvard School of Public Health (HSPH)
name: Wafaie W Fawzi, MBBS, DrPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.