CTRI Number	CTRI/2018/02/012119 [Registered on: 23/02/2018] Trial Registered Retrospectively
Last Modified On:	05/03/2018
Post Graduate Thesis	No
Type of Trial	Interventional
Type of Study	Nutraceutical
Study Design	Randomized, Parallel Group, Active Controlled Trial
Public Title of Study	Non-inferiority of Lower Dose Calcium Supplementation During Pregnancy
Scientific Title of Study Modification(s)	A cluster randomized trial to demonstrate the equivalency of lower dose calcium supplementation during pregnancy for reducing preeclampsia and preterm birth.
Secondary IDs if Any Modification(s)	Secondary ID  Registry  NCT03350516  ClinicalTrials.gov
Details of Principal Investigator or overall Trial Coordinator (multi-center study) Modification(s)	Name  Dr Anura V Kurpad  Address  St Johns National Academy of Health Sciences Sarjapura Road Bangalore KARNATAKA 560034 India  Phone  910849466349   Fax     Email  a.kurpad@sjri.res.in
Details Contact Person Scientific Query Modification(s)	Name  Dr Pratibha Dwarkanath  Address  St Johns National Academy of Health Sciences Sarjapura Road Bangalore KARNATAKA 560034 India  Phone  910849466326   Fax     Email  pratibha@sjri.res.in
Details Contact Person Public Query Modification(s)	Name  Dr Pratibha Dwarkanath  Address  St Johns National Academy of Health Sciences Sarjapura Road Bangalore KARNATAKA 560034 India  Phone  910849466326   Fax     Email  pratibha@sjri.res.in
Source of Monetary or Material Support	Bill and Melinda Gates Foundation, USA
Primary Sponsor	Name  Bill Melinda Gates Foundation USA  Address  Bill & Melinda Gates Foundation, P.O Box 23350, Seattle, WA 98102, US  Type of Sponsor  Other [Non-operating private foundation ]
Details of Secondary Sponsor	Name  Address  Harvard TH Chan School of Public Health  Harvard T.H Chan, School of Public Health, Boston, ma 02115, USA
Countries of Recruitment	India United Republic of Tanzania
Sites of Study Modification(s)	No of Sites = 5   Contact Person  Name of Site  Site Address  Phone/Fax/Email  Andreas Pembe  Africa Academy for Public Health  Plot #802, Mwai Kibaki Road, Mikocheni P.O. Box 79810 Dar es Salaam, Tanzania. Not Applicable   255227771623 andreapembe@yahoo.co.uk  Dr Anura V Kurpad  Banashankari Referral Hospital  Banashankari Referral Hospital,17th Main 27th Cross BsK 2nd Stage Bangalore   08049466349 a.kurpad@sjri.res.in  Dr Anura V Kurpad  H. Siddaiah Road Hospital  Next to Lions Eye Hospital, Off J. C. Road, H. Siddaiah Road Bangalore   08049466349 a.kurpad@sjri.res.in  Honorati Masanja  Ifakara Health Institute  Plot 463, Kiko Avenue Mikocheni Dar es Salaam P.O. Box 78 373 Not Applicable   255222774756 hmasanja@ihi.or.tz  Dr Anura V Kurpad  Ulsoor BBMP Maternity Hospital  Cambridge Road, Ulsoor, Bengaluru, Karnataka 560008 Bangalore   08049466349 a.kurpad@sjri.res.in
Details of Ethics Committee Modification(s)	No of Ethics Committees= 3   Name of Committee  Approval Status  Africa Academy for Public Health,Institutional Review Board of the Ifakara Health Institute,Tanzania  Approved  Institutional Review Board of the Ifakara Health Institute, Tanzania  Approved  St. Johns Instituitional Ethical Commiittee  Approved
Regulatory Clearance Status from DCGI	Status  Not Applicable
Health Condition / Problems Studied	Health Type  Condition  Healthy Human Volunteers  Apparent healthy pregnant women in the age group 18-40 years within 20 weeks of gestation
Intervention / Comparator Agent	Type  Name  Details  Comparator Agent  Active Comparator: Daily 1500 mg Calcium (Standard dose)  Dietary Supplement: Daily 1500 mg elemental calcium as calcium carbonate 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.   Intervention  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
Inclusion Criteria	Age From  18.00 Year(s) Age To  40.00 Year(s) Gender  Female  Details  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
ExclusionCriteria	Details  History or signs and/or symptoms of nephrolithiasis Prior diagnosis of parathyroid disorder or thyroidectomy Diseases that require digoxin, phenytoin, or tetracycline therapy
Method of Generating Random Sequence	Computer generated randomization
Method of Concealment	Pharmacy-controlled Randomization
Blinding/Masking	Participant, Investigator, Outcome Assessor and Date-entry Operator Blinded
Primary Outcome Modification(s)	Outcome  TimePoints  1)Proportion of pregnant women with incident preeclampsia 2) Proportion of preterm birth   1)Proportion of pregnant women with incident preeclampsia will be assessed by the end of recruitment phase and the last subject delivered. 2) Proportion of preterm birth will be assessed at birth
Secondary Outcome	Outcome  TimePoints  Pregnancy complications of hypertension such as gestational proteinuria, early onset preeclampsia or eclampsia, placental abruption, HELLP syndrome Adverse birth outcomes such as early preterm births, low birth weight, small for gestational age birth, still birth, neonatal death and perinatal death   During pregnancy At birth
Target Sample Size	Total Sample Size="22000" Sample Size from India="11000"
Phase of Trial	Phase 3
Date of First Enrollment (India) Modification(s)	15/01/2018
Date of First Enrollment (Global)	05/03/2018
Estimated Duration of Trial	Years="3" Months="4" Days="0"
Recruitment Status of Trial (Global) Modification(s)	Not Yet Recruiting
Recruitment Status of Trial (India)	Open to Recruitment
Publication Details Modification(s)	The study has not generated any results as yet, so NIL publications at this stage. We anticipate publications to arise directly out of this trial based on the objectives such as: 1) Low dose of calcium intervention is beneficial to women from India during pregnancy in reducing pre-eclampsia and preterm births. 2) Low dose of calcium intervention is beneficial to women from Tanzania during pregnancy in reducing pre-eclampsia and preterm births. Low dose calcium supplementation improves the acceptability and compliance in India and Tanzania as compared to the standard 1500 mg calcium/d.
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.