A Placebo Controlled, Randomised Evaluation of an Eight Week Primaquine Regimen for the Treatment of Vivax Malaria.
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 150
- 主要终点
- Primary Efficacy Variable: Proportion with relapse(s) of P. vivax in 12 months of follow-up.
研究概览
简要总结
Plasmodium vivax represents a major health problem throughout the tropics. Outside Africa it accounts for over 50% of cases, affecting an estimated 70-80 million people per year. A substantial proportion of clinical cases are not caused by infective bites of Anopheles spp, but by activation of latent hypnozoites in the liver. These relapses may significantly impede development since each illness may result in 5-15 days of absence from work or school.
Primaquine(PQ) is the only drug available that eliminates hypnozoites, though its use is beset by clinical problems; it may precipitate haemolytic anaemia in individuals deficient in the blood enzyme glucose 6 phosphate dehydrogenase (G6PD). Without affordable G6PD testing, primaquine use is precluded. Evidence suggests, however, that a course of 8 weekly doses may be a safe and effective alternative to the traditional 14 day course of the drug. The aim of the proposed study, therefore, is to test whether 8 weekly doses of primaquine is as effective as the 14 day course at preventing relapse malaria, without the risk of hemolysis in G6PD deficient individuals.
详细描述
Old evidence suggests that successful PQ therapy is not a function of the length of the course of treatment, nor the circulating concentration of the drug, but of the total dosage administered. The same dose administered over 7 days, 14 days, and 8 weeks equally prevented relapse in vivax malaria. The hemolysis seen in shorter courses is often self-limiting, suggesting that feedback mechanisms up-regulate production of red cells in response to haemolytic challenge. The proposed extended course is likely to be well tolerated in G6PD deficient individuals as a result of these safeguards, especially in this population which has been exposed to the 5 day PQ regimen for a number of years without reported adverse effects.
The aim of the study, therefore, is to test whether an 8 week regimen proves effective, without the associated risk of haemolysis in G6PD deficient individuals. However, operational concerns remain about adherence to this protracted treatment regimen. Therefore we will compare the 8 week course in 2 different groups; the first to be directly observed dosing, the second to be unsupervised dosing using pre-packaged, foil wrapped PQ in appropriately labelled individual boxes, supplied with strong health education messages. This would be appropriate for deployment in a resource-poor setting if it proved effective and safe.
Objectives:
To evaluate whether an eight week primaquine regimen, using single weekly doses, can provide adequate radical cure of vivax malaria under experimental and operational conditions and is safe in and acceptable to a population with glucose 6 phosphate dehydrogenase deficiency. The specific objectives of the study are set out below.
- Determine the efficacy of an eight-week primaquine regime, using single weekly doses, in preventing relapses of P. vivax infections following supervised versus unsupervised administration of the drug.
- Compare the efficacy and operational aspects (e.g. adherence) between the two week, eight week supervised and eight week blister package regimes.
- Monitoring of the effect of 8 week PQ on G6PD deficient individuals.
- Examine the user acceptability and economic advantages of this course of treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 3 Years 至 70 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients diagnosed with P. vivax parasitaemia
- •Patients over 3 years
- •Patients with G6PD deficiency to a safety trial
- •Patients without G6PD deficiency to all other groups.
排除标准
- •Children under the age of three
- •Pregnant / breast feeding women
- •Patients with severe clinical anaemia [Hb<7g/dl]
- •Patients with P. falciparum
- •Patients unavailable for the duration of study.
- •Patients who have taken antimalarial drugs in the 2 weeks prior to consultation.
- •Patients with concomitant infections or whose general health is considered too poor.
结局指标
主要结局
Primary Efficacy Variable: Proportion with relapse(s) of P. vivax in 12 months of follow-up.
时间窗: 2004-March 2007
次要结局
- Number of relapse episodes in 12 months(2004-March 2007)
- Side effects / adverse events(2004-March 2007)
- Secondary Efficacy Variables: Time to subsequent relapse episode(2004-March 2007)
研究者
Brian Greenwood
Professor
London School of Hygiene and Tropical Medicine