Feasibility of High Daily Dose Short Course Primaquine After G6PD Testing for the Radical Cure of Plasmodium Vivax Malaria
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 2,999
- 试验地点
- 6
- 主要终点
- Proportion of patients experiencing at least one Serious Adverse Event (SAE) during treatment
研究概览
简要总结
The proportion of malaria that is the Plasmodium vivax species is increasing in Indonesia. Reducing vivax malaria will require innovative solutions to cure both the blood and liver stages of the disease. This study will evaluate of the feasibility of implementing point-of-care glucose-6-phosphate dehydrogenase deficiency (G6PD) testing. This will be followed by high dose, short course primaquine treatment regimens for patients with vivax malaria, and combined with patient education, surveillance, and pharmacovigilance. We plan to implement the study at 6 health facilities across Indonesia using a staged before-and-after study, with a mixed method evaluation.
详细描述
Significant gains have been made in reducing the overall burden of malaria worldwide, however these have been far greater for Plasmodium falciparum than P. vivax. P. vivax remains a major obstacle to malaria control and elimination efforts, largely due to its ability to form dormant liver stages (hypnozoites) that allow it to escape detection and treatment. Importantly, they are susceptible only to 8 aminoquinolines such as primaquine however, primaquine is associated with risk of haemolysis in individuals with a genetic condition, called glucose-6-phosphate dehydrogenase (G6PD) deficiency.
Additionally, the recommended 14-day prolonged treatment regimen is associated with poor treatment adherence hence ineffective primaquine treatment. Innovative solutions to the radical cure of both the blood and liver stages of P. vivax are urgently required.
The Indonesian Ministry of Health has requested a pragmatic study of the feasibility and cost-effectiveness of implementing point-of-care G6PD testing followed by high-dose, short-course primaquine treatment regimens for patients with vivax malaria. These interventions are to be combined with practicable enhancements to patient education, supervision, malariometric surveillance and pharmacovigilance.
This will be a before-after longitudinal health facility-based study implemented at six sites in Indonesia; four in Papua, one in North Sumatra and one in Lampung. We will use a staged approach for the implementation of the revised case management strategy, including patient education and counselling,community-based clinical review, with mixed methods evaluation.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 6 Months 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with vivax malaria
排除标准
- •Patients who are pregnant
- •Patients who are breastfeeding
- •Patients with a Hb <8g/dL
- •Patients with a previous adverse reaction to primaquine
- •Patient with severe malaria
研究组 & 干预措施
Revised case management package
干预措施: Revised case management package (Combination Product)
结局指标
主要结局
Proportion of patients experiencing at least one Serious Adverse Event (SAE) during treatment
时间窗: During treatment (up to 8 weeks) ]
SAEs are collected during clinical review using a study-specific questionnaire
Proportion of patients experiencing at least one Adverse Event of Special Interest(AESI) during treatment
时间窗: During treatment (up to 8 weeks)
AESIs (haemolysis, methaemoglobinaemia and gastrointestinal discomfort) are collected during clinical review using a study-specific questionnaire
Proportion of patients with P. vivax malaria who correctly receive all components of the revised case management package
时间窗: 3 days
Measured by completion of G6PD testing and the correct prescription of primaquine based on G6PD activity, completion of patients counselling and community based follow up on Day 3
次要结局
- Proportion of patients who were reviewed on Day 3 and Day 7(1 week)
- Proportion of patients receiving a SD Biosensor G6PD test(1 day)
- Proportion of P. vivax malaria patients who are ineligible for daily primaquine and are incorrectly given primaquine (including infants, pregnant females and G6PD deficient patients(1 day)
- The proportion of patients with any AESI during treatment(During treatment (up to 8 weeks))
- The proportion of patients with a gastrointestinal (GI) AESI during treatment(During treatment (up to 8 weeks))
- The proportion of patients with an AESI related to haemolysis during treatment(During treatment (up to 8 weeks) ])
- The proportion of patients an AESI related to methaemoglobinaemia(During treatment (up to 8 weeks))
- The proportion of patients receiving correct treatment based on G6PD activity(1 day)
- Proportion of health care practitioners who comply with the revised radical cure treatment algorithm(1 day)
- Proportion of patients permanently stopping PQ before end of treatment(During treatment (up to 8 weeks))
- Perception of and experience with new radical cure tools among health care providers and community members(6 months)
- Proportion of P. vivax malaria patients that are reviewed on Day 3(3 days)
- Proportion of eligible P. vivax malaria patients receiving the correct dose of primaquine based on the result of the G6PD test(1 day)
- Barriers and enablers of uptake and implementation at the sub-national levels are identified(18 months)
- Perceptions of the new radical cure tools and serious adverse events at the community level identified(18 months)
- Costs of implementing policy from a healthcare provider perspective, including health systems strengthening processes(18 months)
- Number of patients with an SAE who are identified by community or clinic staff follow-up and referred to hospital for further management(During treatment (up to 8 weeks))
- Proportion of P. vivax malaria patients that adhere to their prescribed primaquine regimen(3 days)
- Factors influencing acceptability and feasibility of the new radical cure tools among health care providers are identified(3 days)
- Required knowledge, skills, and training to administer the revised case management and patient-counselling identified(18 months)
- The prevalence of P. vivax parasitaemia in patients presenting with fever before implementation versus after implementation(18 months)
- Household costs per P. vivax episode(3 days)
- Overall cost-effectiveness of changing policy if revised case management is effective(18 months)
- Cost per episode of P. vivax malaria from the healthcare provider and societal perspectives(18 months)
- Cost per component of the revised case management package(18 months)
- Factors influencing compliance with G6PD testing and perceptions of new drug regimens and serious adverse events among health care providers are identified(18 months)
- Factors influencing the barriers and facilitators to patient adherence to primaquine after the rollout of the revised case management identified(18 months)
- Factors influencing the acceptability and feasibility of community-based clinical review at Day 3 of primaquine treatment identified(18 months)
- Local acceptability of the revised case management algorithms among patients, their families, and healthcare workers established(Day 3)
- The monthly incidence of confirmed symptomatic P. vivax malaria episodes (mono-infection or mixed) before implementation versus after implementation(18 months)
- Proportion of CHWs who correctly act on early signs of haemolytic anaemia and GI events (i.e. refer patients for further medical review, instruct patient to discontinue treatment)(3 days)
- Cumulative risk of representation to the same clinic with symptomatic P. vivax malaria within 6 months(18 months)
- If revised case management package is effective (significantly reduces the incidence of malaria), then the cost-effectiveness of implementing the revised case management as compared with usual care(18 months)
- The proportion of patients eligible to receive PQ who had a SAE during treatment(During treatment (up to 8 weeks))
- Prevalence of severe anaemia in patients presenting with fever before and after implementation(18 months)