A Prospective Randomized Open-Label Study on the Efficacy and Safety of Intermittent Preventive Treatment in Pregnancy (IPTp) With Dihydroartemisinin-Piperaquine (DP) Versus IPTp With Sulfadoxine-Pyrimethamine (SP) in Malawi
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 602
- 试验地点
- 1
- 主要终点
- Malaria infection at the time of delivery
研究概览
简要总结
This study aims to compare the efficacy of monthly IPTp-DP with monthly IPTp-SP to determine if IPTp-DP is associated with a reduction in malaria infection at delivery among HIV-negative women in an area with high levels of SP resistance in Malawi.
详细描述
Problem to be studied Malaria in pregnancy (MiP) due to Plasmodium falciparum infection is a major cause of maternal morbidity and poor birth outcomes in malaria-endemic countries. Pregnant women are at increased risk of more frequent and severe malaria infections than non-pregnant women. Intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP), which involves administration of treatment doses of SP at each antenatal visit in the second and third trimesters of pregnancy, at least one month apart, irrespective of malaria parasitemia, is currently recommended for all women, except HIV positive women taking daily cotrimoxazole prophylaxis, in areas with stable moderate to high transmission of malaria.
SP is the only drug currently used for IPTp. Due to increasing resistance to SP, it is no longer used as a treatment for symptomatic malaria, however, IPTp-SP remains effective even in areas where SP resistance in children under five (determined by in vivo efficacy studies) is up to 26%, and continues to be used for IPTp in countries where SP is no longer recommended to treat symptomatic malaria. However, IPTp-SP has become more controversial given recent data from northern Tanzania and Malawi that have demonstrated that at higher rates of resistance, IPTp-SP may no longer be effective.
Alternative drugs which could replace SP have been tested; mefloquine, azithromycin-chloroquine, and amodiaquine have been abandoned as options due to poor tolerability among pregnant women. Dihydroartemisinin-Piperaquine (DP) remains an attractive option because of the long half-life of piperaquine (PQ) and the demonstrated efficacy, safety, and tolerability in pregnancy. Recent studies in Kenya and Uganda using DP for IPTp demonstrated a significant reduction in the prevalence of malaria throughout pregnancy and at the time of delivery. However, there was not a clear benefit in terms of improved neonatal outcomes. Additional studies are therefore needed to determine the impact of switching from IPTp-SP to IPTp-DP.
Study aims Primary objectives To compare the efficacy of monthly IPTp-DP with monthly IPTp-SP to determine if IPTp-DP is associated with a reduction in malaria infection at delivery among HIV-negative women in an area with high levels of SP resistance in Malawi.
Secondary objectives
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 16 Years 至 —（Child, Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Viable singleton pregnancy
- •Gestational age ≤28 completed weeks (28 6/7) by fundal height/ultrasound
- •Maternal age ≥16 years
- •No history of IPTp use during this pregnancy
- •Willing to participate and complete the study schedule, including laboratory studies and delivery in the labor ward of the study clinic or hospital
- •Willing to sign or thumb print informed consent
- •Resident of study area and intending to stay in the area for the duration of the follow-up
- •HIV-negative at enrolment
排除标准
- •HIV-positive or unknown
- •Multiple gestation
- •High-risk pregnancy, including any pre-existing illness likely to cause complication of pregnancy (hypertension, diabetes, asthma, epilepsy, renal disease, liver disease, fistula repair, leg or spine deformity)
- •Severe anemia requiring blood transfusion (Hb <7.0 g/dL) at enrolment
- •Known allergy or previous adverse reaction to any of the study drugs
- •Previous inclusion in the same study
- •Participating in other malaria intervention studies
- •Known or suspected cardiac disease
- •Corrected QT interval (QTcF) greater than 450 ms at baseline
- •Patients taking any of the following drugs:
- •Antimicrobial agents of the following classes (systemic use only):
- •Macrolides (e.g. erythromycin, clarithromycin, azithromycin, roxithromycin)
- •Fluoroquinolones (e.g., levofloxacin, moxifloxacin, sparfloxacin)
- •Pentamidine
- •Antiarrhythmic agents (e.g. amiodarone, sotalol)
- •Antihistamines (e.g. promethazine)
- •Antifungals (systemic): ketoconazole, fluconazole, itraconazole
- •Antiretrovirals: Saquinavir
- •Diuretics (e.g. hydrochlorothiazide, furosemide)
- •Antipsychotics (neuroleptics): haloperidol, thioridazine
- •Antidepressants: imipramine, citalopram, escitalopram
- •Antiemetics: domperidone, chlorpromazine, ondansetron
研究组 & 干预措施
dihydroartemisinin-piperaquine
Intermittent preventive treatment with dihydroartemisinin-piperaquine: Monthly course of daily doses of co-formulated DP tablets containing 40 mg dihydroartemisinin and 320 mg piperaquine, dosed based on the woman's weight, for 3 days:
- 24-35.9 kg: Two tablets
- 36-59.9 kg: Three tablets
- 60-79.9 kg: Four tablets
- ≥80 kg: Five tablets
干预措施: dihydroartemisinin-piperaquine (Drug)
Sulfadoxine-pyrimethamine
Intermittent preventive treatment with Sulfadoxine-pyrimethamine: Monthly dose of 3 co-formulated tablets containing 500 mg sulfadoxine and 25 mg pyrimethamine
干预措施: Sulfadoxine-pyrimethamine (Drug)
结局指标
主要结局
Malaria infection at the time of delivery
时间窗: delivery
The composite of peripheral and placental parasitemia, detected by placental histology, positive peripheral blood smear at the time of delivery, or positive rapid diagnostic test at the time of delivery
Fetal morbidity
时间窗: Delivery
Composite endpoint of fetal morbidity, defined as any of the following: Preterm birth (birth before 37 weeks gestation), Low-birth-weight (birth weight under 2,500 grams), Small for gestational age (SGA)
次要结局
- Serious adverse events(From date of randomization until the date of delivery or last date of follow-up, average of ~4-5 months)
- Incidence of clinical malaria episodes(From date of randomization until the date of delivery or last date of follow-up, average of ~4-5 months)
- Maternal anemia at 3rd trimester(3rd trimester)
- Fetal anemia(Delivery)
- Electrocardiogram changes following the receipt of DP(4-6 hours after the 3rd dose with each course)
- Incidence of all cause sick visits(From date of randomization until the date of delivery or last date of follow-up, average of ~4-5 months)
- Microbiome changes following receipt of DP or SP(From date of randomization until the date of delivery or last date of follow-up, average of ~4-5 months)
- Maternal hemoglobin at 3rd trimester(3rd trimester)
研究者
Julie Gutman
Medical epidemiologist
Kamuzu University of Health Sciences