Pregnancy RelatedPhase 3NCT03350516
Non-inferiority of Lower Dose Calcium Supplementation During Pregnancy
A Phase 3 study testing Daily 500 mg elemental calcium as calcium carbonate and Daily1500 mg elemental calcium as calcium carbonate in people with Pregnancy Related, run by Harvard School of Public Health (HSPH) at 3 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, women onlyHealthy volunteers can take part
- Conditions the study is for
- Pregnancy Related
- What is being tested?
- Daily 500 mg elemental calcium as calcium carbonate and Daily1500 mg elemental calcium as calcium carbonate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22,000 participants
- Where
- 3 sitesin 2 countries
- Study dates
- 30 Nov 2018to 16 Dec 2022
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- History or signs and/or symptoms of nephrolithiasis
- Prior diagnosis of parathyroid disorder or thyroidectomy
- Diseases that require digoxin, phenytoin, or tetracycline therapy
Trial locations and contacts
3 sites in 2 countries.
3 sites in 2 countries
Tanzania2 sites
Africa Academy for Public Health
Dar es Salaam
Ifakara Health Institute
Dar es Salaam
About this study
Official title: 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.
- Conditions
- Pregnancy Related
- Being tested
- Daily 500 mg elemental calcium as calcium carbonate, Daily1500 mg elemental calcium as calcium carbonate
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Daily 500 mg elemental calcium as calcium carbonateDietary supplement
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.
Daily1500 mg elemental calcium as calcium carbonateDietary supplement
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.
| Study group | Role | What they receive |
|---|---|---|
| Daily 500 mg Calcium | Experimental | Not described Receives: Dietary Supplement: Daily 500 mg elemental calcium as calcium carbonate |
| Daily1500 mg Calcium (Standard dose) | Active comparator | Not described Receives: Dietary Supplement: Daily1500 mg elemental calcium as calcium carbonate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of pregnant women with incident preeclampsia
Measured: Gestational week 20 to Delivery
Proportion of preterm birth
Measured: Birth
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Nov 2017
- Study start30 Nov 2018
- Primary completion3 Nov 2022
- Study completion16 Dec 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Pregnancy RelatedStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 22,000 participants (actual)
Sponsor and investigators
- Lead sponsor
- Harvard School of Public Health (HSPH)
- Sponsor type
- University, hospital or other
- Collaborators
- St. John's Research Institute, Ifakara Health Institute, Africa Academy for Public Health
- Responsible party
- Principal investigator, Wafaie Fawzi, Harvard School of Public Health (HSPH)
- Investigators
- Wafaie W Fawzi, MBBS, DrPH, Principal investigator, Harvard School of Public Health (HSPH)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03350516
- Sponsor's protocol ID
- OPP1172660
- Status last verified
- Dec 2024
- First submitted
- 19 Nov 2017
- Last updated
- 24 Dec 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 38197817Ali NB, Sudfeld CR, Muhihi A, Thomas T, Perumal N, Sando MM, Masanja HM, Partap U, Duggan CP, Kurpad AV, Dwarkanath P, Pembe AB, Fawzi WW. Effect of calcium supplementation in pregnancy on maternal anemia and iron status: secondary analyses of two randomized trials in India and Tanzania. Am J Clin Nutr. 2026 Jul;124(1):101338. doi: 10.1016/j.ajcnut.2026.101338. Epub 2026 Apr 30.
PubMed 42067065Pembe AB, Dwarkanath P, Kikula A, Raj JM, Perumal N, Paulo HA, M R, Duggan CP, Masanja HM, Chopra N, Sando MM, Thomas T, Yelverton CA, Muhihi A, Kurpad AV, Fawzi WW, Wylie BJ, Sudfeld CR. Hypertensive disorders of pregnancy and perinatal outcomes: two prospective cohort studies of nulliparous women in India and Tanzania. BMJ Glob Health. 2025 Jul 10;10(7):e016339. doi: 10.1136/bmjgh-2024-016339.
PubMed 40639854Dwarkanath 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.
PubMed 34819147
Study at a glance
From the registry record, last updated by the sponsor on 24 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Demonstrating Non-inferiority of Lower Dose Calcium Supplementation During Pregnancy for Reducing Preeclampsia and Neonatal Outcomes
- ClinicalTrials.gov ID
- NCT03350516
- Acronym / sponsor ID
- OPP1172660
- Conditions
- Pregnancy Related
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22,000 participants (actual)
- Lead sponsor
- Harvard School of Public Health (HSPH)University, hospital or other
- Collaborators
- St. John's Research Institute, Ifakara Health Institute, Africa Academy for Public Health
- Study start
- 30 Nov 2018 (actual)
- Primary completion
- 3 Nov 2022 (actual)
- Study completion
- 16 Dec 2022 (actual)
- First posted
- 22 Nov 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Daily 500 mg Calcium | Experimental | Dietary Supplement: Daily 500 mg elemental calcium as calcium carbonate |
| Daily1500 mg Calcium (Standard dose) | Active comparator | Dietary Supplement: Daily1500 mg elemental calcium as calcium carbonate |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (3 listed)
- History or signs and/or symptoms of nephrolithiasis
- Prior diagnosis of parathyroid disorder or thyroidectomy
- Diseases that require digoxin, phenytoin, or tetracycline therapy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Daily 500 mg elemental calcium as calcium carbonatePregnant 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. | Dietary supplement | Daily 500 mg Calcium |
| Daily1500 mg elemental calcium as calcium carbonatePregnant 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. | Dietary supplement | Daily1500 mg Calcium (Standard dose) |
Primary outcome
Proportion of pregnant women with incident preeclampsia
Time frame: Gestational week 20 to Delivery
Proportion of preterm birth
Time frame: Birth
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Dec 2024.
- Results publication: PubMed 38197817Dwarkanath 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.
- Derived from this study: PubMed 42067065Ali NB, Sudfeld CR, Muhihi A, Thomas T, Perumal N, Sando MM, Masanja HM, Partap U, Duggan CP, Kurpad AV, Dwarkanath P, Pembe AB, Fawzi WW. Effect of calcium supplementation in pregnancy on maternal anemia and iron status: secondary analyses of two randomized trials in India and Tanzania. Am J Clin Nutr. 2026 Jul;124(1):101338. doi: 10.1016/j.ajcnut.2026.101338. Epub 2026 Apr 30.
- Derived from this study: PubMed 40639854Pembe AB, Dwarkanath P, Kikula A, Raj JM, Perumal N, Paulo HA, M R, Duggan CP, Masanja HM, Chopra N, Sando MM, Thomas T, Yelverton CA, Muhihi A, Kurpad AV, Fawzi WW, Wylie BJ, Sudfeld CR. Hypertensive disorders of pregnancy and perinatal outcomes: two prospective cohort studies of nulliparous women in India and Tanzania. BMJ Glob Health. 2025 Jul 10;10(7):e016339. doi: 10.1136/bmjgh-2024-016339.
- Derived from this study: PubMed 34819147Dwarkanath 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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Wafaie W Fawzi, MBBS, DrPH principal investigator
Harvard School of Public Health (HSPH)
3 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Daily 500 mg elemental calcium as calcium carbonate and Daily1500 mg elemental calcium as calcium carbonate in people with Pregnancy Related, run by Harvard School of Public Health (HSPH) at 3 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Tanzania, India. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of pregnant women with incident preeclampsia (time frame: Gestational week 20 to Delivery). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03350516, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Dec 2024.