An Open-label in Vivo Drug Study to Evaluate the Pharmacokinetics, Therapeutic Efficacy, Gametocyte Carriage and Birth Outcomes Following Sulfadoxine-pyrimethamine Intermittent Presumptive Treatment (SP IPT) in Pregnant Women
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 31
- 试验地点
- 1
- 主要终点
- Pharmacokinetic parameters by measurement of whole blood levels of sulfadoxine and pyrimethamine and plasma levels of artesunate to determine Cmax, Tmax, AUC, half life, volume of distribution and clearance
研究概览
简要总结
The main purpose of this study is to compare the drug levels of sulfadoxine-pyrimethamine found when given to pregnant women for the prevention of malaria to those found in pregnant women given the same drug with artesunate for the treatment of malaria, and also with those drug levels found in non-pregnant women in other malaria treatment studies.
详细描述
Pregnancy increases the risk of malaria progression and complications with up to a 10-fold increase in the malaria case fatality rate in areas of low transmission. Sulfadoxine-pyrimethamine (SP) is used widely in Africa for the systematic intermittent presumptive, or preventive, treatment (IPTp) during the second and third trimester of pregnancy and a national program of IPTp with SP has been implemented recently in Mozambique. There is evidence that the kinetics of several other antimalarial drugs are altered in pregnancy to the extent that doses are not adequate in pregnancy, however no published study has included a pharmacokinetic component to confirm that standard doses of SP are optimal in this vulnerable patient group. This study therefore creates the opportunity to study whether the pharmacokinetic properties of SP are altered by physiological changes that occur during pregnancy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- 否
入选标准
- •Pregnant female, older than 18 years, > 35kg.
- •Gestational age > 16 weeks (fundal height > 16cm) and below 36 weeks gestation.
- •Documented informed consent.
- •Lives close enough to the study site for reliable follow up and is willing to attend ANC and follow-up visits regularly.
排除标准
- •Diagnoses of uncomplicated acute P. falciparum malaria parasitaemia
- •Has received anti-malarial treatment in the past 7 days and/or sulfadoxine-pyrimethamine in the past 28 days.
- •Known hepatic or renal impairment
- •Has received chloramphenicol, cotrimoxazole or tetracyclines (including doxycycline) in the past 7 days or is likely to require these during the study period.
- •History of G6PD deficiency.
- •Has a history of allergy to any of the study drugs (including other sulphonamides e.g. cotrimoxazole).
- •Serious underlying disease that in the opinion of the clinic team and/or Principal Investigator would make the patient unsuitable for the study in terms of their safety or study analysis.
- •Imminent delivery expected.
- •Prior inclusion in this study.
研究组 & 干预措施
SP plus artesunate
SP (Fansidar®, Roche South Africa) at a dose of 25/1.25mg/kg of sulfadoxine/pyrimethamine respectively on day 0 only, and artesunate (Arsumax®, Sanofi-Aventis, South Africa) at a dose of 4mg/kg on days 0, 1, and 2
干预措施: sulfadoxine-pyrimethamine (Drug)
结局指标
主要结局
Pharmacokinetic parameters by measurement of whole blood levels of sulfadoxine and pyrimethamine and plasma levels of artesunate to determine Cmax, Tmax, AUC, half life, volume of distribution and clearance
时间窗: 0 hours (pre treatment) and repeated on day 0 or 1 at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours, and days 2, 3, 7, 14, 21, 28 and 42
次要结局
- Correlation of treatment outcome and gametocyte carriage with pharmacokinetic parameters and pregnancy status(0 hours (pre treatment) and repeated on day 0 or 1 at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12 and 24 hours, and days 2, 3, 7, 14, 21, 28 and 42 , and time of birth outcome)
- Correlation of frequency of DHFR mutations at codons 436, 437, 540 and 581 in maternal and placental samples with treatment outcomes(Day 42 (or day of withdrawal))
- Birth outcomes in terms of major congenital abnormalities, spontaneous abortions, still births and neonatal deaths, gestational age and birth weight, placental weight, newborn head circumference, arm circumference and neurological development(Day of birth outcome)
- Risk of harm by describing all adverse events and their causality assessments and changes in full blood count, glucose, bilirubin, creatinine, urea and ALT(Days 3, 7, 14, 21, 28 and every 2 weeks thereafter until birth (for a minimum of 42 days) or withdrawal visit)
- Capacity building by describing the training and development of study teams and their subsequent skills attained(Duration of trial)
研究者
Professor Karen I Barnes
Professor, Clinical Pharmacology
University of Cape Town