Intravenous Versus Oral Iron for Iron Deficiency Anaemia in Pregnant Nigerian Women (IVON): an Open Label, Randomized Controlled Trial
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 1,056
- 试验地点
- 11
- 主要终点
- Prevalence of maternal anemia at 36 weeks' gestation
研究概览
简要总结
Background: Anaemia in pregnancy is a public health burden with high incidence in Africa. Currently high dose oral iron is recommended for treatment of mild to moderate anaemia and blood transfusion for severe anaemia. The high dose oral iron is often poorly tolerated and associated with several side effects. Various parenteral iron preparations are now available for treatment of iron deficiency anaemia (IDA). The earliest of these, iron dextran is not commonly used because of its potential to cause anaphylactic reactions. Newer preparations have been found to be safer and their use for treatment of IDA is currently being evaluated.
Objective: This study sought out to compare the effectiveness of intravenous ferric carboxymaltose (intervention) versus oral ferrous sulphate (control) for treating IDA in pregnancy and to compare the tolerability, safety and the cost-effectiveness of intravenous versus oral iron among pregnant Nigerian women with moderate and severe IDA at 20-32 weeks' gestation.
Methodology: This study will be a hybrid Type 1 effectiveness-implementation design. 1056 eligible and consenting pregnant women with anaemia at 20 - 32 weeks gestation will be recruited. They will be randomized into either of 2 groups. Group A will have intravenous ferric carboxymaltose 20mg/kg to a maximum of 1000mg in 200mls of normal saline infusion over 15 - 20 minutes at enrolment. Group B will have oral ferrous sulphate 200mg (65mg elemental iron) thrice daily from enrolment till delivery. They will be followed up through delivery and until 6 weeks post partum. Their haemoglobin concentration, full blood count, serum ferritin and serum transferrin will be assayed at specific intervals using standard laboratory techniques. Depression will be assessed at each visit using Edinburg Postnatal Depression Scale. Cost effectiveness analysis will also be done at each visit. The primary outcome measure will be incidence of maternal anaemia and rise in haemoglobin level. Secondary outcome measures will include safety and tolerability of trial drugs, severe maternal events, incidence of infant low birth weight and incidence of depression. Statistical analysis will be done using STATA version 16.0 statistical software (STATACorp, Texas, USA).
详细描述
1.0 INTRODUCTION Anemia in pregnancy (AIP) remains a critical global health problem especially in low- and middle-income countries (LMICs), affecting 46% of pregnant women in Africa and 49% in Asia. AIP is defined as a venous blood hemoglobin concentration of <11 g/dl in a pregnant woman. Iron deficiency anemia (IDA) is the commonest cause of AIP, accounting for 50-75% of AIP. Antenatal maternal anemia has significant implications on both maternal and neonatal outcomes, including maternal mortality from hemorrhage and morbidity from infections, and neonatal low birth weight and prematurity. It has also been associated with an increased risk of depression.
In most LMICs, including Nigeria, routine treatment of IDA in pregnancy is with oral iron preparations, due to fears of serious adverse reactions from parenteral iron, including anaphylaxis, and the belief that oral iron is equally effective. Parenteral, especially intravenous, iron is also more expensive, and it is not clear whether its benefits are worth the cost. In settings like Nigeria, where most people still pay out-of-pocket for healthcare, cost effectiveness is particularly important. However, apart from the side effects caused by oral iron, it also takes longer to correct the anemia, and in cases where patients are unable to absorb iron, oral intake is rendered ineffective. Reservations on use of parenteral iron have been due largely to experience with high molecular weight iron dextran preparations, which had a relatively high incidence of anaphylactic reactions. Fortunately, there are now several safe parenteral iron preparations, such as iron sucrose, iron polymaltose, ferric carboxymaltose (FCM) and iron isomaltoside.
2.0 AIMS AND OBJECTIVES Aims: To determine the comparative effectiveness of intravenous FCM (intervention) versus oral ferrous sulphate (control) for treating iron deficiency anemia in pregnancy and to compare the tolerability, safety, and the cost-effectiveness of intravenous versus oral iron among pregnant Nigerian women with moderate and severe IDA at 20-32 weeks' gestation. It also aims to evaluate the acceptability, feasibility, and fidelity of use of intravenous FCM for treating IDA.
Objectives
- To determine effect of intravenous FCM on the prevalence of maternal anemia at 36 weeks' gestation and on increase in hemoglobin concentration 4 weeks after administration, compared with oral ferrous sulphate (FS) in pregnant women with IDA.
- To determine effect of intravenous FCM on incidence of postpartum hemorrhage, sepsis, shock, need for blood transfusion, prevalence of depression and other maternal clinical outcomes, compared with oral FS in pregnant women with IDA.
- To determine effect of intravenous FCM on the incidence of low infant birthweight, prematurity, stillbirth, and neonatal mortality, and on breastfeeding and immunization, compared with use of oral FS in pregnant women with IDA.
- To measure implementation outcomes of intravenous FCM including its acceptability, feasibility, and fidelity in the context in which the trial is being carried out.
- To determine cost-effectiveness of intravenous FCM compared with oral FS in treatment of IDA in pregnancy.
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
入排标准
- 年龄范围
- 15 Years 至 49 Years（Child, Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Pregnant women aged 15 to 49 years old between 20*- and 32**-weeks' gestational age.
- •Baseline (enrollment) laboratory-confirmed moderate or severe anemia (Hb < 10g/dl).
排除标准
- •Medically-confirmed significant bleeding, major surgery or received blood transfusion within the last 3 months.
- •Severe symptomatic anemia needing urgent correction with blood transfusion.
- •Anemia of other cause besides IDA e.g., Sickle cell anemia.
- •Clinically-confirmed malabsorption syndrome.
- •Hypersensitivity to any form of iron treatment.
- •History of any immune related illness e.g., SLE, Rheumatoid arthritis.
- •Preexisting maternal depression or other psychiatric illness.
- •Severe allergic reactions such as severe asthma.
- •History of severe drug allergy.
研究组 & 干预措施
FCM - Intravenous Ferric carboxymaltose
Intravenous Ferric Carboxymatlose administered in a single dose of 20mg/Kg to a maximum of 1000mg in 200mls of infusion given over minimum of 15 - 20 minutes at enrollment.
干预措施: Ferric carboxymaltose (Drug)
FS -Oral Ferrous sulphate
Oral Ferrous Sulphate (containing 65mg of elemental iron) to be taken as one 200mg tablet 3 times a day until delivery.
干预措施: Ferrous sulfate (Drug)
结局指标
主要结局
Prevalence of maternal anemia at 36 weeks' gestation
时间窗: Measurement taken at 36 weeks gestational age
To be collected from data source on number of women with hemoglobin concentration less than 10g/dl as determined by hemocue.
Incidence of preterm delivery
时间窗: Data will be collected following delivery.
Measured using data source. Preterm delivery is defined as all births after 28 weeks gestational age but before 37 completed weeks of gestation.
次要结局
- Proportion of patients with severe maternal events, specifically, haemorrhage, sepsis, shock and the need for blood transfusion measured using data source at delivery(Measured at delivery)
- The incidence of low infant birthweight, prematurity, stillbirth and neonatal mortality, proportion of infants being breastfed at 1, 2 and 4 weeks of life, and receiving BCG, oral polio and hepatitis vaccination in same time period(Measurements will be taken at delivery, 1,2 and 4 weeks post delivery)
- The incidence of depression linked to emotional well-being of mothers using the validated Edinburgh Postnatal Depression Scale measured at enrolment, 36 weeks gestational age and 7 days post delivery(Measurements taken at enrolment, 36 weeks gestational age and 7 days post delivery)
- Maternal hemoglobin levels at 4 weeks post-initiation of treatment(Measurement taken at 4 weeks post-initiation of treatment)
- Prevalence of maternal iron deficiency at 36 weeks' gestation(Measurement taken at 36 weeks gestational age)
- Proportion of patients with side effects or intolerance to medication in FCM vs. FS group, including incidence of hypophosphatemia and severe maternal adverse effects at Day 1 and 4 weeks post enrolment, at 36 weeks gestation and 6 weeks post delivery(Assessment to be done on Day 1 and 4 weeks post enrolment, at 36 weeks gestational age and at 6 weeks post delivery)
研究者
Bosede Bukola Afolabi
Professor
University of Lagos, Nigeria