Division of Nutrition, St. John's Research Institute, Bangalore, India.
Africa Academy for Public Health, Dar es Salaam, Tanzania.
Trials. 2021 Nov 24;22(1):838. doi: 10.1186/s13063-021-05811-7.
Hypertensive disorders of pregnancy are important causes of maternal morbidity and mortality, as well as preterm birth, the leading cause of death for children under 5 years globally. The World Health Organization currently recommends that pregnant women receive high-dose calcium supplementation (1500-2000 mg elemental calcium) for prevention of preeclampsia in populations with low dietary calcium intake. Trials of low-dose calcium supplementation (< 1000 mg elemental calcium/day) during pregnancy have also shown similar reductions in the risk of preeclampsia; however, no trials to date have directly compared low-dose to the standard high-dose calcium supplementation. Our objective is to assess the non-inferiority of low-dose as compared to standard high-dose calcium supplementation in pregnancy.
METHODS/DESIGN: We will conduct two independent trials in Bangalore, India (n = 11,000 pregnancies), and Dar es Salaam, Tanzania (n = 11,000 pregnancies). The trial designs are individually randomized, parallel group, quadruple-blind, non-inferiority trials of low-dose calcium supplementation (500 mg elemental calcium/day) as compared to standard high-dose calcium supplementation (1500 mg elemental calcium/day) among nulliparous pregnant women. Pregnant women will be enrolled in the trial before 20 weeks of gestation and will receive the randomized calcium regimen from randomization until the time of delivery. The co-primary outcomes are (i) preeclampsia and (ii) preterm birth; we will test non-inferiority of the primary outcomes for low-dose as compared to the standard high-dose supplementation regimen in each trial. The trials' secondary outcomes include gestational hypertension, severe features of preeclampsia, pregnancy-related death, third trimester severe anemia, fetal death, stillbirth, low birthweight, small-for-gestational age birth, and infant death.
The trials will provide causal evidence on the non-inferiority of low-dose as compared to the standard high-dose supplementation in India and Tanzania. A single tablet, low-dose calcium supplementation regimen may improve individual-level adherence, reduce programmatic costs, and ultimately expand implementation of routine calcium supplementation in pregnancy in populations with low dietary calcium intake.
ClinicalTrials.gov identifier: NCT03350516 ; registered on 22 November 2018. Clinical Trials Registry-India identifier: CTRI/2018/02/012119 ; registered on 23 February 2018. Tanzania Medicines and Medical Devices Authority Trials Registry identifier: TFDA0018/CTR/0010/5 ; registered on 20 December 2018.
妊娠高血压疾病是孕产妇发病率和死亡率的重要原因，也是全球 5 岁以下儿童死亡的主要原因。世界卫生组织目前建议，低膳食钙摄入人群的孕妇应接受高剂量钙补充剂（1500-2000mg 元素钙）以预防子痫前期。在妊娠期间进行低剂量钙补充剂（<1000mg 元素钙/天）的试验也显示出类似降低子痫前期风险的效果；然而，迄今为止尚无试验直接比较低剂量与标准高剂量钙补充剂。我们的目标是评估低剂量与妊娠期间标准高剂量钙补充剂相比的非劣效性。
方法/设计：我们将在印度班加罗尔（n=11000 例妊娠）和坦桑尼亚达累斯萨拉姆（n=11000 例妊娠）进行两项独立试验。试验设计为个体随机、平行分组、四重盲、非劣效性试验，比较低剂量钙补充剂（500mg 元素钙/天）与标准高剂量钙补充剂（1500mg 元素钙/天）在初产妇中的应用。孕妇将在妊娠 20 周前入组试验，并从随机分组开始至分娩时接受随机钙治疗方案。主要结局为（i）子痫前期和（ii）早产；我们将在每个试验中检验低剂量与标准高剂量补充方案相比的主要结局的非劣效性。试验的次要结局包括妊娠期高血压、子痫前期严重特征、妊娠相关死亡、孕晚期严重贫血、胎儿死亡、死产、低出生体重、小于胎龄儿出生和婴儿死亡。
这些试验将提供关于低剂量与标准高剂量补充剂在印度和坦桑尼亚的非劣效性的因果证据。单一片剂、低剂量钙补充方案可能会提高个体依从性、降低项目成本，并最终扩大低膳食钙摄入人群常规妊娠钙补充的实施。
ClinicalTrials.gov 标识符：NCT03350516；于 2018 年 11 月 22 日注册。印度临床试验注册中心标识符：CTRI/2018/02/012119；于 2018 年 2 月 23 日注册。坦桑尼亚药品和医疗器械管理局试验注册中心标识符：TFDA0018/CTR/0010/5；于 2018 年 12 月 20 日注册。
