A Safety, Tolerability, Pharmacokinetic and Efficacy Study of Azithromycin Plus Piperaquine as Presumptive Treatment in Pregnant Papua New Guinean Women
试验速览
- 阶段
- 4 期
- 入组人数
- 150
- 试验地点
- 1
- 主要终点
- Efficacy of azithromycin plus piperaquine for the prevention of malaria during pregnancy
研究概览
简要总结
Plasmodium falciparum parasitaemia in pregnancy is associated with maternal anaemia, low birth-weight and increased perinatal mortality. Whilst continuous prophylaxis is difficult to implement, intermittent presumptive treatment in pregnancy (IPTp) has proved to be practical and effective. In PNG, pregnant women currently receive IPTp using sulfadoxine-pyrimethamine, however, this therapy has the potential to be compromised by parasite resistance.
The aim of the present trial is to assess the safety, tolerability, pharmacokinetics and efficacy of azithromycin (AZI) plus piperaquine (PQ) given as IPTp to pregnant Papua New Guinea women. The study will comprise of two sub-studies:
(i) A safety, tolerability and pharmacokinetic study of AZI-PQ in pregnancy. (ii) A safety, tolerability and preliminary efficacy study of AZI-PQ 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
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •>14 weeks and <30 weeks gestation
- •No signs of severe malaria by World Health Organisation criteria
- •No significant concomitant disease (such as TB)
- •No prior history of an adverse reaction to AZI or PQP
- •No prior treatment with these drugs in the past 4 weeks
- •Can attend all follow-up visits
- •Provide informed consent
排除标准
- •Have signs of severe malaria by WHO criteria
- •Significant concomitant disease such as TB as assessed by the attending clinician
- •A history/family history of sudden death or of congenital prolongation of the QTc interval
- •Any clinical condition known to prolong the QTc interval
- •A history of complicated pregnancies/deliveries
- •A prior history of an adverse reaction to AZI or PQP
- •Have taken these drugs in the past 4 weeks
- •Cannot attend any of the follow-up visits
- •Do not provide informed consent
研究组 & 干预措施
Efficacy Study: Azithromycin plus piperaquine
At baseline, participants receive three daily doses (0, 24 and 48 hours) of i) 1 g azithromycin as 2 x film-coated 500 mg tablets ii) 960 mg piperaquine tetraphosphate tablets as 3 x 320 mg tablets
干预措施: Azithromycin plus piperaquine phosphate (Drug)
Efficacy Study Control: National Standard Treatment
At baseline, participants receive a single dose of sulfadoxine-pyrimethamine comprising 1,500 mg of sulfadoxine and 75 mg pyrimethamine in tablet form
干预措施: Sulfadoxine-pyrimethamine (Drug)
Pharmacokinetic Study: Azithromycin plus piperaquine
At baseline, participants receive three daily doses (0, 24 and 48 hours) of i) 1 g azithromycin as 2 x film-coated 500 mg tablets ii) 960 mg piperaquine tetraphosphate tablets as 3 x 320 mg tablets
干预措施: Azithromycin plus piperaquine phosphate (Drug)
结局指标
主要结局
Efficacy of azithromycin plus piperaquine for the prevention of malaria during pregnancy
时间窗: 42 days intensive follow-up, final end-point at 2 weeks post delivery
The efficacy of azithromycin plus piperaquine for the prevention of malaria infection during pregnancy will be investigated in 120 women. Women will be randomized to receive either (i) 3 daily doses of AZI plus PQ, or, (ii) single dose sulfadoxine-pyrimethamine Participants will be actively followed for a period of 42 days (1, 2, 3, 4, 7, 14, 21, 28 and 42 days after treatment). At each follow-up time point the participant will have a clinical examination, fundal height measurement and assessment of foetal lie, perform a symptoms questionnaire, blood film for malaria and other scheduled safety tests (eg. Hb, glucose, ultrasound). A single blood sample for pharmacokinetic analysis will be collected at Day 4. At delivery all participants and their babies will be assessed, including blood sample for Hb, glucose, blood spot for PCR, cord blood and maternal blood. Breast milk samples will be collected for 2 weeks (Day 1, 2, 3, 4, 7, 14) after the establishment of lactation.
次要结局
- Pharmacokinetics - distribution, terminal elimination and absorption half-life(t1/2) of azithromycin and piperaquine(42 days intensive follow-up, final end-point at 2 weeks post delivery)
- Pharmacokinetics - peak plasma concentration (Cmax) of azithromycin and piperaquine(42 days intensive follow-up, final end-point at 2 weeks post delivery)
- Pharmacokinetics - area under the plasma concentration versus time curve (AUC) of azithromycin and piperaquine(42 days intensive follow-up, final end-point at 2 weeks post delivery)
- Pharmacokinetics - volume of distribution (Vd) of azithromycin and piperaquine(42 days intensive follow-up, final end-point at 2 weeks post delivery)
- PCR adjusted 42 day cure(42 days)
- Number of participants with adverse events as a measure of safety and tolerability(42 days intensive follow-up, final end-point at 2 weeks post delivery)
- Pharmacokinetics - clearance (CL) of azithromycin and piperaquine(42 days intensive follow-up, final end-point at 2 weeks post delivery)
- PCR adjusted 28 day cure(28 days)