IPTp With Dihydroartemisinin-piperaquine and Azithromycin for Malaria, Sexually Transmitted and Reproductive Tract Infections in Pregnancy in High Sulphadoxine-pyrimethamine Resistance Areas in Kenya, Malawi and Tanzania
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 4,680
- 试验地点
- 7
- 主要终点
- Adverse pregnancy outcome
研究概览
简要总结
This study evaluates the efficacy and safety of monthly intermittent preventive treatment using dihydroartemisinin piperaquine (DP) alone or in combination with azithromycin (AZ) compared to sulphadoxine-pyrimethamine (SP) for the prevention of malaria in pregnant women in the second and third trimester.
详细描述
Intermittent preventive treatment with sulphadoxine-pyrimethamine (IPTp-SP) is one of the pillars of malaria prevention in pregnancy in sub-Saharan Africa, in addition to prompt case management and use of long lasting insecticide treated bednets. However, mounting resistance to SP by Plasmodium falciparum increasing renders IPTP-SP ineffective.
Two exploratory trials in Uganda and Kenya demonstrated that IPTp with DP was superior to IPTp-SP for the prevention of malaria infection in pregnancy. However, neither study was adequately powered to look at adverse birth outcomes. This study is a confirmatory efficacy trial in Malawi, Tanzania and Kenya to determine the efficacy and safety of IPTp with DP alone or in combination with AZ.
This will be a 3-arm trial, superiority, partial blinded, placebo controlled, randomized trial comparing IPTp with SP, versus IPTp with DP alone, and IPTp with DP+AZ with the following hypotheses:
- IPTp with DP is superior to IPTp with SP in preventing adverse pregnancy outcomes.
- The combination of DP with AZ further reduces adverse pregnancy outcomes compared to IPTp with DP alone.
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
The study will be a partially placebo-controlled involving a single placebo for AZ. To further minimise bias, an objective primary outcome measure will be used and all staff will be masked to the treatment assignment of individual women. The trial statistician will also be masked in regard to the treatment code when he develops the statistical analysis plan and writes the statistical programmes, which will be validated and completed using dummy randomisation codes. The actual allocation will only be provided to the study team after locking of the database and approval of the statistical analysis plan by the independent Data Monitoring and Ethics Committee (DMEC) before they review any trial results. The study statistician conducting the interim analysis will remain masked throughout the analysis.
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
- •Pregnant women between 16-28 weeks' gestation
- •Viable singleton pregnancy
- •Resident of the study area
- •Willing to adhere to scheduled and unscheduled study visit procedures
- •Willing to deliver in a study clinic or hospital
- •Provide written informed consent
排除标准
- •Multiple pregnancies (i.e. twin/triplets)
- •HIV-positive
- •Known heart ailment
- •Severe malformations or non-viable pregnancy if observed by ultrasound
- •History of receiving IPTp-SP during this current pregnancy
- •Unable to give consent
- •Known allergy or contraindication to any of the study drugs
研究组 & 干预措施
IPTp-SP
Stat course of 3 tablets of quality-assured SP (tablets of 500 mg of sulphadoxine and 25 mg of pyrimethamine) at each scheduled antenatal visit
干预措施: sulphadoxine-pyrimethamine (Drug)
IPTp-DP
Dihydroartemisinin-piperaquine [3 to 5 tablets of DP (tablets of 40 mg of dihydroartemisinin and 320 mg of piperaquine, based on bodyweight) daily for 3 days] + placebo AZ at each scheduled antenatal visit
干预措施: dihydroartemisinin-piperaquine (Drug)
IPTp-DPAZ
Dihydroartemisinin-piperaquine [3 to 5 tablets of DP (tablets of 40 mg of dihydroartemisinin and 320 mg of piperaquine, based on bodyweight) daily for 3 days] + AZ tablet [1.5g over 3 days as 500mg per day] at each scheduled antenatal visit.
干预措施: dihydroartemisinin-piperaquine plus azithromycin (Drug)
结局指标
主要结局
Adverse pregnancy outcome
时间窗: 8 months
Composite of foetal loss (spontaneous abortion or stillbirth), or singleton live births born small-for-gestational age (SGA), or with low birthweight (LBW), or preterm (PT) (SGA-LBW-PT), or subsequent neonatal death by day 28.
次要结局
- LBW(6 months)
- Placental malaria detected by molecular methods (PCR)(6 months from randomisation)
- QTc-prolongation(6 months from randomisation)
- Congenital malformations(6 months from randomisation)
- Other SAEs and AEs(8 months from randomisation)
- (History of) vomiting study drug(6 months from randomisation)
- Molecular markers of drug resistance in Plasmodium falciparum infections during pregnancy and delivery(6 months from randomisation)
- Neonatal length and stunting(8 months)
- Maternal nutritional status(6 months from randomisation)
- Maternal anaemia during pregnancy and delivery(6 months from randomisation)
- Congenital anaemia(6 months from randomisation)
- Composite of foetal loss and neonatal mortality(8 months)
- SGA-LBW-PT composite(6 months)
- SGA(6 months)
- Congenital malaria infection(6 months from randomisation)
- Gastrointestinal complaints(6 months from randomisation)
- PT(6 months)
- Placental malaria detected by microscopy(6 months from randomisation)
- Placental malaria detected by histology(6 months from randomisation)
- Clinical malaria during pregnancy(6 months from randomisation)
- Malaria infection during pregnancy detected by microscopy and PCR(6 months from randomisation)
- Composite placental malaria detected by microscopy, by molecular methods or by histology(6 months from randomisation)
- Maternal mortality(8 months from randomisation)
- Dizziness(6 months from randomisation)
- Changes in the colony composition of maternal vaginal microbiota, and intestinal microbiota of mother and infant.(6 months from randomisation)
- Presence of STIs/RTIs prior to delivery (syphilis, gonorrhoea, Chlamydia trachomatis, Trichomonas vaginalis, and bacterial vaginosis)(6 months from randomisation)
- Changes in macrolide resistance in Pneumococcus detected in maternal nasopharyngeal samples(6 months from randomisation)