Evaluation of the Safety and Efficacy of Dihydroartemisinin-piperaquine for Intermittent Preventive Treatment of Malaria in HIV-infected Pregnant Women
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 666
- 试验地点
- 2
- 主要终点
- Maternal parasitaemia at delivery
研究概览
简要总结
Trial to evaluate the safety and efficacy of DHA-PPQ for Intermittent Preventive Treatment (IPTp) in HIV-infected pregnant women receiving cotrimoxazole prophylaxis (CTXp) and antiretroviral (ARV) drugs and using long lasting insecticide treated nets will be conducted in Mozambique and Gabon where malaria and HIV infection are moderate to highly prevalent. In addition, the possibility for a PK interaction between DHA-PPQ and ARV drugs will be assessed in a sub-sample of participants. Women will receive ARV therapy according to national guidelines and their infants will be followed until one year of age to evaluate the impact of DHA-PPQ on MTCT-HIV.
详细描述
Background
Intermittent preventive treatment in pregnancy (IPTp) with sulphadoxine-pyrimethamine (SP) is recommended for malaria prevention in HIV-uninfected women but it is contraindicated in those HIV-infected on cotrimoxazole prophylaxis (CTXp) due to potential adverse effects. A recent trial showed that an effective antimalarial added to CTXp and long-lasting insecticide treated nets (LLITNs) in HIV-infected pregnant women improves malaria prevention and maternal health. However, the antimalarial used -mefloquine- was not well tolerated and it was associated with an increase in HIV viral load at delivery and a two-fold increased risk of MTCT-HIV. These findings highlight the need to find alternative drugs with better tolerability and safety profile to prevent malaria in this vulnerable group and to further study the pharmacological interactions between antimalarials and antiretrovirals (ARVs).
Dihydroartemisinin-piperaquine (DHA-PPQ), because of its long half-life and good tolerability has been shown to improve antimalarial protection in HIV-uninfected pregnant women, constituting the most promising candidate for IPTp in HIV-infected pregnant women. However, there is limited information on the pharmacokinetics of DHA-PPQ with concomitant use of ARV drugs and CTX, particularly in pregnant women.
Objectives
- To evaluate the safety, tolerability and efficacy of DHA-PPQ as IPTp for malaria prevention in HIV-infected pregnant women receiving daily CTXp and ARV drugs
- To assess the effect of DHA-PPQ as IPTp on mother to child transmission of HIV
- To study the effects of DHA-PPQ on the pharmacokinetics of clinically relevant doses of ARV drugs used for prevention of MTCT and treatment of HIV infection
- To evaluate the effectiveness of CTXp in clearing malaria parasites in HIV-infected pregnant women
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Double blind placebo-controlled
入排标准
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Permanent resident in the study area
- •Gestational age at the first antenatal visit ≤ 28 weeks
- •HIV seropositive status
- •Agreement to deliver in the study site's maternity(ies) wards
排除标准
- •Residence outside the study area or planning to move out in the following 10 months from enrolment
- •Gestational age at the first antenatal visit > 28 weeks of pregnancy
- •Known history of allergy to CTX
- •Known history of allergy or contraindications to DHA-PPQ
- •Participating in other intervention studies
研究组 & 干预措施
IPTp-DHA-PPQ
Monthly IPTp-DHA-PPQ over three days plus daily ARVs and cotrimoxazole prophylaxis
干预措施: Dihydroartemisinin-piperaquine (DHA-PPQ) (Drug)
IPTp-Placebo
Monthly IPTp-placebo over three days plus daily ARVs and cotrimoxazole prophylaxis
干预措施: Placebo Oral Tablet (Drug)
结局指标
主要结局
Maternal parasitaemia at delivery
时间窗: Delivery
Presence of Plasmodium falciparum (P. falciparum) asexual parasites of any density in peripheral blood (determined by microscopy)
次要结局
- Incidence of clinical malaria(During first year of life)
- Incidence of all-cause admissions(On average six months follow up during pregnancy)
- Incidence of all-cause outpatient attendances(On average six months follow up during pregnancy)
- Frequency and severity of adverse events(On average six months follow up during pregnancy)
- Mean haemoglobin concentration(At delivery)
- Prevalence of submicroscopic P. falciparum peripheral parasitaemia(At delivery)
- Prevalence of anaemia (Hb<11 g/dL)(At delivery)
- Prevalence of severe anaemia (Hb<7 g/dL)(At delivery)
- Mean CD4+ T cell counts levels(At delivery)
- Proportion of women with detectable HIV viral load(At delivery)
- Prevalence of placental P. falciparum infection(At delivery)
- Prevalence of P. falciparum peripheral parasitaemia at the post-partum visit(On average 42 days after end of pregnancy (post-partum visit))
- Maternal mortality rate(On average six months follow up during pregnancy and 42 days after end of pregnancy (post-partum visit))
- Prevalence of P. falciparum parasitaemia in cord blood(At birth)
- Prevalence of neonatal anaemia(Neonatal period ( in first 28 days of life))
- Composite adverse pregnancy outcome(Birth)
- Mean birth weight(At birth)
- Prevalence of low birth weight (<2500 g)(At birth)
- Mean gestational age at birth(At birth)
- Prevalence of prematurity(At birth)
- Prevalence of embryo and foetal losses(On average six months follow up during pregnancy)
- Prevalence of small for gestational age(At birth)
- Frequency of congenital malformations(At birth)
- Neonatal mortality rate(During neonatal period (during first 28 days of life))
- Frequency of mother to child transmission of HIV at one and at 12 months of age(During first year of life)
- Infant mortality rate(During first year of life)
- Composite malaria outcome: proportion of participants with malaria infection diagnosed(From enrolment until one month after end of pregnancy (on average seven months of study follow up of women, depending on gestational age at inclusion))
- Composite maternal malaria and anemia: proportion of particiapnts diganosed either with malaria or anemia(At delivery)