Reducing Anemia in Pregnancy in India: the RAPIDIRON Trial
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 4,368
- 试验地点
- 4
- 主要终点
- Return to non-anemic status in the last trimester of pregnancy
研究概览
简要总结
Anemia is a worldwide problem with iron deficiency being the most common cause. When anemia occurs in pregnancy, it increases the risk of adverse maternal, fetal, and postnatal outcomes. Anemia rates are among the highest in South Asia, with a recent national survey indicating that over half of pregnant women in India are classified as anemic. For nearly 40 years, India's first-level treatment for anemia in pregnancy has been oral iron; however, side effects, poor adherence to tablet ingestion, and low therapeutic impact are among reasons to consider a new paradigm for treatment of pregnant women with iron deficiency anemia (IDA). Reducing Anemia in Pregnancy in India: the RAPIDIRON Trial is a 3-arm, randomized-controlled trial designed to assess if a single dose of an intravenous (IV) iron formulation, administered early in the second trimester of pregnancy for treatment of moderate IDA, will result in a greater proportion of participants in the IV iron arms achieving a normal hemoglobin concentration in the third trimester when compared to participants randomized to receive oral iron. This trial is also designed to test the hypothesis that the low birth weight (LBW) rate for participants randomized to the IV iron arms will be lower when compared to the LBW rate of those randomly assigned to the oral iron arm. The three arms include two IV iron arms (arm 1 - ferric carboxymaltose, arm 2 - iron isomaltoside, also known as ferric derisomaltose) and an active, comparator arm receiving oral iron, which is the standard of care. This study will be conducted in two states in India - Karnataka and Rajasthan. This study supports the overall goals of the Indian Ministry of Health and Family Welfare for pregnancy care; thus, all study participants will be followed according to the Ministry's antenatal care guidelines, and data will be collected through 42 days post-delivery.
(see attached protocol for more detail)
详细描述
Anemia is a worldwide problem with iron deficiency being the most common cause. When occurring in pregnancy, anemia increases the risk of adverse maternal, fetal and neonatal outcomes, including maternal mortality, preterm and low birth weight (LBW) deliveries, perinatal and neonatal deaths, and long-term developmental sequelae in the surviving offspring. Anemia rates are among the highest in south Asia, and India's latest National Family Health Survey (NFHS-5) for 2019-21 indicates that anemia with hemoglobin (Hb) <11.0 g/dL affects over 50% of pregnant women.
Optimal fetal, neonatal and childhood brain growth and development require adequate iron. However, women with moderate to severe anemia during the late 2nd and early 3rd trimesters of pregnancy are often unable to make up their iron deficit. Thus, despite active transport via the placenta, insufficient iron may be transmitted to the developing fetus with consequent negative sequelae, including long-term neurodevelopmental impairment of the newborn.
For close to 40 years, India's first-level treatment for anemia in pregnancy has been oral iron; however, side effects, poor adherence to tablet ingestion and low therapeutic impact are among reasons for consideration of a new paradigm for treatment of pregnant women with iron deficiency anemia. The Government of India has given high priority to reducing the prevalence of anemia in India, and several initiatives have been directed at this objective. The latest anemia strategy, built on prior strategies and supported by the Ministry of Health and Family Welfare, was presented in a 2018 publication, Anemia Mukt Bharat-Intensified National Iron Plus Initiative. The same overall strategy remains in effect, but a few changes have been made to specific intervention guidelines. The updated guidelines can be viewed online. Notably, this research focuses on pregnant women, one of the population groups targeted by Anemia Mukt Bharat which has the goal of reducing prevalence of anemia among children, adolescents and women in the reproductive age group by 3% a year. The current anemia strategy, supported by the RAPIDIRON Trial, can help facilitate India's efforts to achieve a 2025 Global World Health Assembly target of a 50% reduction of anemia among women of reproductive age.
Reducing Anemia in Pregnancy in India: the RAPIDIRON Trial is a 3-arm, randomized-controlled trial. The study intervention is a single dose of an intravenous (IV) formulation - ferric carboxymaltose in arm 1 or iron isomaltoside (also known as ferric derisomaltose) in arm 2 - administered early in the second trimester of pregnancy for treatment of moderate iron deficiency anemia (IDA). The third arm is an active, comparator arm consisting of oral iron, which is the standard of care. For this trial, approximately 4,320 pregnant women with moderate IDA across four research sites in the Indian states of Karnataka and Rajasthan will be randomized with a one-to-one-to-one ratio to the three study arms.
The two primary hypotheses of this trial are as follows:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
盲法说明
Oral iron use will not be masked (as tablets will be provided). However, blinding will occur for the two IV iron intervention arms, as participants, primary health center (PHC) staff, and community health center (CHC) infusion teams will only know that participants have been randomly assigned to receive an IV iron infusion without knowing the specific arm and formulation to be used. A pharmacist associated with each CHC performing infusions for the trial will be designated to prepare the randomly assigned IV iron formulation (according to participant weight and manufacturer instructions) on the day of treatment.
入排标准
- 年龄范围
- 18 Years 至 40 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- •Fetal anomaly, if detectable when an initial ultrasound is done to date the pregnancy (subsequent discovery of a fetal anomaly is not viewed as an exclusion criterion);
- •History of cardiovascular disease, hemoglobinopathy, or other disease or condition considered a contraindication for treatment, including conditions recommended for exclusion by the manufacturers of oral or IV iron to be used in this study;
- •Any condition that, in the opinion of the consenting physician, warrants study exclusion.
研究组 & 干预措施
IV iron intervention arm 1
Intervention arm 1 involves a single dose of an IV iron formulation - ferric carboxymaltose - given during pregnancy.
干预措施: Ferric carboxymaltose (Drug)
IV iron intervention arm 2
Intervention arm 2 involves a single dose of an IV iron formulation - iron isomaltoside - given during pregnancy.
干预措施: Iron isomaltoside (Drug)
Active comparator
Participants randomly assigned to the active comparator arm will receive oral iron tablets to take daily, which is the current standard of care.
干预措施: Ferric Sulfate (Drug)
结局指标
主要结局
Return to non-anemic status in the last trimester of pregnancy
时间窗: 30-34 week antenatal visit or prior to delivery
Return to non-anemic status, defined as hemoglobin concentration ≥11 g/dL, measured at either a 30-34 week antenatal visit or prior to delivery
Low birth weight (<2500 grams) deliveries
时间窗: Delivery/birth
Low birth weight (\<2500 grams) deliveries
次要结局
- Changes in ferritin(After randomization to 42 days post-delivery)
- Offspring ferritin from cord blood(Delivery/birth)
- Weight gain(After randomization to delivery)
- Incidence of hemorrhage(Delivery/birth)
- Offspring transferrin saturation from cord blood(Delivery/birth)
- Incidence of hypertensive disorders(After randomization to 42 days post-delivery)
- Changes in offspring hemoglobin measured from cord blood(Delivery/birth)
- Mode of delivery/incidence of c-section(Delivery/birth)
- Incidence of maternal mortality(After randomization to 42 days post-delivery)
- Time from delivery to cord clamping(Within 72 hours of birth)
- Incidence of breastfeeding(42 days after delivery)
- Referral for evaluation due to little improvement(26-30 weeks of pregnancy)
- Incidence of preterm and small for gestational age births(Delivery/birth)
- Changes in hemoglobin concentration by moderate anemia subgroups(30-34 week antenatal visit or prior to delivery)
- Changes in transferrin saturation(After randomization to 42 days post-delivery)
- Incidence of maternal infections(After randomization to 42 days post-delivery)
- Incidence of neonatal mortality(After randomization to 42 days post-delivery)
- Well-being/quality of life(42 days after delivery)
- Incidence of need for 'rescue therapy'(After randomization to delivery)
- Incidence of neonatal infections(After randomization to 42 days post-delivery)
- Newborn weight(Measured within 72 hours of delivery)
- Incidence of neonatal resuscitation(Within 72 hours of birth)
- Incidence of neonatal admissions to an intensive care unit(Birth to 28 days of life)
- Incidence of unscheduled healthcare visits(After randomization to 42 days post-delivery)
- Incidence of pregnancy loss and stillbirth(After randomization to delivery)
- Newborn length(Measured within 72 hours of delivery)