Serological Testing and Treatment for Plasmodium Vivax Malaria: a Cluster-Randomised Trial in Ethiopia and Madagascar
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 19,200
- 试验地点
- 2
- 主要终点
- Proportion of individuals with PCR detectable P. vivax blood-stage infections 6 months after the second round of PvSeroTAT or 6 months after the second round of blood sampling in the control clusters.
研究概览
简要总结
The resilience of P. vivax to malaria elimination efforts is due to its ability to form dormant liver stages (hypnozoites) that reactivate weeks to months after the initial infection causing recurrent episodes of malaria (relapses) and ongoing parasite transmission. Relapses account for a majority of recurrent infections and clinical cases of P. vivax malaria, and therefore have a significant effect on morbidity at the individual level.
With current technology, it is not possible to directly measure hypnozoite biomarkers. Rather than directly detecting hypnozoites, our team developed an indirect approach by measuring antibodies induced by the primary blood-stage infection. Antibodies to different blood-stage antigens decay at different rates. Measuring antibodies to a carefully selected panel of P. vivax antigens can aid to identify individuals who have been infected within the previous 9 months (approximately the lifespan of hypnozoites).
A serological test based on selected P. vivax antigens can detect recent exposure and predict future relapses. Coupling this test with a safe and efficacious primaquine treatment regimen, results in a population-based intervention to target the hypnozoite reservoir. This intervention is referred to as Plasmodium vivax Serological Testing and Treatment (PvSeroTAT).
PvSTATEM is a cluster randomised trial in Madagascar and Ethiopia. This study will provide insights into the feasibility, acceptability, and efficacy of the PvSeroTAT approach. In this study, individuals, randomised by clusters, will be tested for the presence of serological markers of a recent P. vivax infection, followed by a targeted drug treatment intervention aimed at killing P. vivax hypnozoites.
详细描述
In each country, 24 clusters (48 clusters in total) will be randomly allocated using computer generated numbers to one of the two interventions:
Arm 1 (PvSeroTAT intervention) or Arm 2 (Control arm). Within each cluster, approximately 400 participants (range 100-600) will be enrolled, based on the trial's inclusion and exclusion criteria. At baseline (month 0) and month 6 serology for P. vivax infections will be performed in all study participants. In the clusters in the PvSeroTAT arm, participants with a positive P. vivax serology at baseline or month 6 will be approached for treatment. First G6PD enzyme activity will be measured. If the enzyme activity is normal and no other contra-indication for treatment are found, the participants will be treated with 14 days of primaquine 0.25mg/kg/day OR 7 days of primaquine 0.5mg/kg (Ethiopia) or 7 days of primaquine 0.5mg/kg/day (Madagascar), and a three-day course of either chloroquine (Ethiopia) or artesunate-amodiaquine (Madagascar). It is possible that a participant could receive a radical P. vivax treatment at both baseline (month 0) and month 6. Participants will be monitored for side effects and adherence during the first 7 days after the start of antimalarial treatments. In addition, blood samples will be taken to measure hemoglobin levels to monitor for post-treatment hemolysis.
In the clusters in both arms, the incidence of malaria will be monitored through passive case detection in health posts up to 18 months after the first intervention. All cases that are detected during the passive case detection will be treated according to the national guidelines.
At month 12 and month 18 of the study, a cross sectional survey will be conducted in all study clusters. Blood samples will be taken to determine the prevalence of P. vivax and P. falciparum through PCR assays.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 12 Months 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participant will remain in the study area for at least the next month.
- •Participant is older than 12 months
排除标准
- •Participant is unwilling to participate.
研究组 & 干预措施
Control arm
干预措施: Control (Diagnostic Test)
PvSeroTAT intervention
干预措施: PvSeroTAT (Combination Product)
结局指标
主要结局
Proportion of individuals with PCR detectable P. vivax blood-stage infections 6 months after the second round of PvSeroTAT or 6 months after the second round of blood sampling in the control clusters.
时间窗: 6 months after the second round of PvSeroTAT or 6 months after the second round of blood sampling in the control clusters.
6 months after the second round of PvSeroTAT, a blood sample will be collected from participants through fingerprick in the intervention clusters. In the control clusters a blood sample to determine PCR prevalence will be collected 6 months after the second round of blood sampling in that control cluster.
次要结局
- Decrease in Hemoglobin between baseline and day 7 (absolute and proportional)(Day 7)
- Incidence of potential signs of clinically relevant Haemolysis(7 days)
- Incidence of Serious Adverse Events(18 months after the first round of PvSeroTAT or 18 months after the first round of blood sampling in the control clusters.)
- Proportion of eligible individuals that refuses participation in the study(Day 0 of month 0 or month 6)
- Coverage of serological tests for P. vivax antibodies as proportion of number of individuals per cluster(Day 0 of month 0 or month 6)
- Proportion of participants with positive P. vivax serology that refuses P. vivax treatment(Day 1 of drug administration)
- Proportion of serological positive individuals that start primaquine treatment(Day 1 of drug administration)
- Proportion of individuals that vomits at least once within 1 hour after treatment(Day of start of treatment until day 7 of treatment)
- Proportion of individuals that vomits twice within 1 hour after treatment.(Day of start of treatment until day 7 of treatment)
- Proportion of individuals with PCR detectable P. vivax blood-stage infections 12 months after the second round of PvSeroTAT or 12 months after the second round of blood sampling in the control clusters.(12 months after the second round of PvSeroTAT or 12 months after the second round of blood sampling in the control clusters.)
- Proportion of individuals with PCR detectable P. vivax blood-stage infections 6 months after the first round of PvSeroTAT (before second round) or 6 months after the first round of blood sampling in the control clusters.(6 months after the first round of PvSeroTAT or 6 months after the first round of blood sampling in the control clusters.)
- Decrease of mean cluster prevalence of PCR detectable P. vivax blood-stage infections at month 6 after the first round of PvSeroTAT or 6 months after the first round of blood sampling in the control clusters, compared to baseline.(6 months after the first round of PvSeroTAT or 6 months after the first round of blood sampling in the control clusters.)
- Decrease of mean cluster prevalence of PCR detectable P. vivax blood-stage infections at month 12 after the first round of PvSeroTAT or 12 months after the first round of blood sampling in the control clusters, compared to baseline.(12 months after the first round of PvSeroTAT or 12 months after the first round of blood sampling in the control clusters.)
- Decrease of mean cluster prevalence of PCR detectable P. vivax blood-stage infections at month 18 after the first round of PvSeroTAT or 18 months after the first round of blood sampling in the control clusters, compared to baseline.(18 months after the first round of PvSeroTAT or 18 months after the first round of blood sampling in the control clusters.)
- Incidence of clinical cases of P. vivax and P. falciparum malaria during the 6 months after the first round of PvSeroTAT or during the 6 months after the first round of blood sampling in the control clusters.(6 months after the first round of PvSeroTAT or 6 months after the first round of blood sampling in the control clusters.)
- Incidence of clinical cases of P. vivax and P. falciparum malaria during the 12 months after the first round of PvSeroTAT or during the 12 months after the first round of blood sampling in the control clusters.(12 months after the first round of PvSeroTAT or 12 months after the first round of blood sampling in the control clusters.)
- Incidence of clinical cases of P. vivax and P. falciparum malaria during the 18 months after the first round of PvSeroTAT or during the 18 months after the first round of blood sampling in the control clusters.(18 months after the first round of PvSeroTAT or 18 months after the first round of blood sampling in the control clusters.)
- Hemoglobin level at day 3(Day 3)
- Hemoglobin level at day 7(Day 7)
- Decrease in Hemoglobin between baseline and day 3 (absolute and proportional)(Day 3)
- Proportion of study participants that complete the 14-day or 7-day course of primaquine treatment.(Day of start of treatment until day 7 of treatment)