Evaluating the Efficacy of Chloroquine for the Treatment of Plasmodium Vivax Infections in Central Vietnam
试验速览
- 阶段
- 4 期
- 发起方
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Number of patients with Adequate Clinical and Parasitological Response (ACPR) at day 42 after treatment with Chloroquine.
研究概览
简要总结
Understanding the extent and regional distribution of CQR vivax malaria and detecting early signs of resistance is critical to prevent the spread of resistant strains, optimize treatment guidelines, and reduce the risk of recurrent and severe malaria. In Vietnam, CQR in P.vivax has been reported sporadically. One study carried out in Binh Thuan province (central-south Vietnam) at the end of the 1990s demonstrated early P.vivax recurrences (7%) by Day 16 after a 3-day CQ treatment. However, in a summary report to World Health Organization (WHO) including data from 11 sentinel sites, from studies conducted between 2006 and 2011 in central and southern Vietnam (total 350 patients), P.vivax is still considered sensitive to CQ. More recently in a cohort study conducted in Quang Nam province (Central Vietnam) in which P.vivax patients were treated radically with CQ and primaquine (10-day at 0.5mg/kg/day) following national guidelines, the 28-day failure rate was measured at 3.45% and CQ blood concentrations measured at day of recurrence (>100ng/ml) confirmed resistance in three patients. The current national guidelines for the radical cure regimen of P.vivax infections recommends 3 days of CQ (total 25 mg/kg body weight (bw)) together with 14 days of primaquine at 0.25 mg/kg bw/ day.
The current WHO protocol recommends a 28-day follow-up to assess the efficacy of CQ for the treatment of P.vivax infections. However, recurrence of early stage resistant parasites may occur after Day 28 in the presence of CQ blood levels above the minimum efficacy concentration (MEC, ≥100ng/ml) and relapses could occur as early as 36 days after standard CQ treatment. Therefore, in order to confirm CQR it is recommended to extend the follow-up period, to Day 42 or 63 and measure whole blood CQ level at Day 28 and at the time of recurrence. Moreover, it has been shown that emerging drug resistance in P.vivax is associated with delayed parasite clearance after treatment, i.e. some parasites are still detectable at Day 3. The aim of the present study is to assess the in vivo and ex vivo susceptibility of P.vivax to CQ in Central Vietnam following the currently recommended radical cure regimen and using GMP certified CQ.
详细描述
3.1 Study Design This study is designed as a 42-day drug efficacy study to evaluate clinical and parasitological responses after treatment of P.vivax malaria infections. Symptomatic patients with P. vivax mono-infections, meeting the study criteria, will be enrolled into the study, and treated with CQ (total dose 25gm/kg over 3 days). The treatment will be directly observed and the patients will be actively followed-up for 42 days according to an extended WHO protocol. At the end of the follow-up time, all patients will be treated with primaquine following national guidelines for the radical cure of P.vivax infections.
3.2 Study Site and Population The study will be carried out in Krong Pa district, Gia Lai province where both P.falciparum and P.vivax malaria incidence are among the highest in the country. The study will be located in Chu'R Cam commune where the study team will be working with the local health staff and all surrounding communes with malaria patients.
The local population is mainly composed by the JaRai ethnic minority and the main occupation consist of slash and burn agriculture (mainly maize, manioc and rice) in forest fields, together with seasonal work in rubber plantations, and small-scale production of goods for daily subsistence or trade e.g. coffee and cashew nuts. The climate is tropical with the dry season from November to April and the rainy season from May to October. The area is hilly and forested (secondary forest) and the main malaria vector is Anopheles dirus.
3.4 Trial Population The target population includes all P.vivax infected patients (children and adults) either presenting spontaneously at the CHC or identified through active screening in the community.
3.5 Trial Procedures 3.5.1 Screening and recruitment All consulting patients who meet the basic enrolment criteria during screening will be assigned a consecutive screening number and evaluated in greater depth by the medical doctor. Once the patient meets all the enrolment criteria, he or she (or a parent or guardian in case of children) will be asked for consent to participate in the study. Then, he/she will be allocated a study number (ID=sequential numbering). Any person who decides not to participate in the study will be examined, treated and followed-up by the health facility staff according to the standard of care established by the Ministry of Health.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 1 Year 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Mono-infection of P. vivax by light microscopy (LM) with asexual parasite density >250/µl
- •Age ≥1year
- •Axillary temperature ≥ 37.5º C and/or history of fever during the previous 48 hours;
- •Patient or caregiver consent to enrolment and agree to sampling and return visits;
排除标准
- •General danger signs or symptoms of severe malaria (as per WHO definitions; Annex I);
- •Signs or symptoms of severe malnutrition, defined as weight-for-age ≤ 3 standard deviations below the mean (NCHS/WHO normalized reference values, Annex II);
- •Slide confirmed infection with any other Plasmodium species (including mixed infections);
- •Severe anaemia, defined as haemoglobin (Hb) <7g/dl in adults and <5g/dl in children;
- •Known hypersensitivity to any of the drugs being evaluated;
- •Presence of fever due to illness other than malaria;
- •History of serious and/or chronic medical condition (cardiac, renal, hepatic diseases, sickle cell disease, HIV/AIDS);
- •Pregnancy (confirmed by rapid test) or breastfeeding;
- •Regular use of medication that may interfere with antimalarial pharmacokinetics;
研究组 & 干预措施
Chloroquine
Single treatment arm
干预措施: Chloroquine (Drug)
结局指标
主要结局
Number of patients with Adequate Clinical and Parasitological Response (ACPR) at day 42 after treatment with Chloroquine.
时间窗: day 42
This outcome will be measured at day42 of follow-up. Treatment outcomes such as ACPR, early or late clinical failures are defined following WHO guidelines;
次要结局
- Ex vivo susceptibility of P. vivax isolates to QN, DHA , PPQ and CQ (Mean IC50 and IC90)(At day0 and day of recurrence of P.vivax parasitemia after initial parasite clearance assessed up to day 42)