Evaluation of Safety and Efficacy of Two Primaquine Dosing Regimens for the Radical Treatment of Plasmodium Vivax Malaria in Vanuatu and Solomon Islands
试验速览
- 阶段
- 不适用
- 入组人数
- 180
- 试验地点
- 4
- 主要终点
- Efficacy: Numbers of Plasmodium vivax relapses per person-years of follow-
研究概览
简要总结
The Melanesian states of the Western Pacific (Papua New Guinea, Solomon Islands and Vanuatu) represent a unique and especially prescient challenge to malaria control and elimination.
While the use of bed nets and other vector control and case management measures have achieved major advances in overall malaria control, the P. vivax and P. ovale species account for an ever-increasing burden of clinical disease.
The lack of effective treatment of the hypnozoite stages of infection with these species result in ongoing relapses and a continuing reservoir of infection.
The only known drug effective for treatment of the hypnozoite stage is primaquine; however the safe and effective dose of this drug in malaria treatment is still unclear.
A recent study evaluated the safety and efficacy of two primaquine dosing regimens (0.25mg/kg and 0.5mg/kg) in a population in New Ireland province, PNG. This study aims to replicate this methodology in Vanuatu and Solomon Islands, to provide a more complete picture of primaquine efficacy and safety in each of the three countries of this region.
详细描述
Study Aims
Primary To define and compare the efficacy of standard (0.25mg/kg/day for 14 days) and high-dose (0.5mg/kg/day for 14 days) primaquine in preventing early relapses from P. vivax in Solomon Islands and Vanuatu.
Secondary To measure safety and toxicity of primaquine when administered as a standard or high-dose regimen in Melanesian adults and children in Solomon Islands and Vanuatu.
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
- 12 Months 至 60 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 12 months to 60 years
- •Melanesian background and living in local area
- •Microscopically (based on field microscopy) or RDT confirmed P.vivax regardless of parasite density. Mixed infections (P.falciparum-P.vivax and P.malariae-P.vivax) can be included.
排除标准
- •Any signs of severe malaria (see WHO definitions) including: impaired consciousness, respiratory distress, severe anaemia (Hb<5), multiple seizures, frequent vomiting/ inability to swallow tablets, prostration, jaundice, hypotension, abnormal bleeding or hypoglycaemia.
- •Clinical evidence of non-malarial illness (such as pneumonia or otitis media)
- •Severe malnutrition (weight-for-age nutritional Z score [WAZ] <60th percentile)
- •Permanent disability, which prevents or impedes study participation.
- •Treatment with primaquine in the previous 14 days
- •Residence or planned travel outside the study area during the follow-up period (precluding supervised treatment and follow-up procedures)
- •Known or suspected pregnancy
- •Currently breastfeeding
- •A positive rapid test for G6PD deficiency (Binax or Carestart RDT)
- •Following later PCR-based confirmation of malaria speciation, there may be some post-hoc exclusion of subjects in whom it is thought the initial field-based microscopic diagnosis may have been incorrect.
研究组 & 干预措施
Standard dose
Participants will receive a standard 3-day treatment course of artemether-lumefantrine at the standard age-based dosage, and will be administered the standard recommended primaquine dose of 0.25mg/kg for 14 consecutive days.
干预措施: Primaquine (Drug)
High dose
Participants will receive a standard 3-day treatment course of artemether-lumefantrine at the standard age-based dosage, and will be administered a primaquine dose of 0.5mg/kg/day for 14 consecutive days.
干预措施: Primaquine (Drug)
Control
Participants will receive a standard 3-day treatment course of artemether-lumefantrine at the standard age-based dosage, but will not receive primaquine until the time of confirmed recurrent parasitaemia or completion of 3 months follow up.
干预措施: delayed primaquine (Drug)
结局指标
主要结局
Efficacy: Numbers of Plasmodium vivax relapses per person-years of follow-
时间窗: 12 months
Total number of microscopically diagnosed (including both symptomatic and asymptomatic infections), PCR-confirmed relapses with Plasmodium vivax in participants in each treatment arm over the 3-month follow-up period, expressed as number of relapses per person-years of follow-up.
次要结局
- Safety and toxicity (5) Numbers with assumed significant haemolysis(12 months)
- Safety and toxicity (1): Numbers with mild adverse events(12 months)
- Safety and toxicity (2) Numbers with moderate adverse events(12 months)
- Safety and toxicity (3) Numbers with severe adverse events(12 months)
- Safety and toxicity (4) Numbers with any adverse events(12 months)
- Safety and toxicity (6) Numbers with significant methaemoglobinaemia(12 months)