Efficacy of Artesunate Monotherapy and Dihydroartemisinin - Piperaquine in Patients With Uncomplicated Falciparum Malaria in Central Vietnam
试验速览
- 阶段
- 4 期
- 发起方
- 入组人数
- 120
- 试验地点
- 1
- 主要终点
- Median parasite clearance time after treatment with Artesunate or with DHA - PIP
研究概览
简要总结
At the end of 2012, the Institute of Tropical Medicine in collaboration with National Institute of Malariology Parasitology and Entomology (NIMPE) conducted a study in Quang Nam province, central Vietnam, to assess the efficacy of the national DHA-PPQ regimen for the treatment of uncomplicated P. falciparum malaria infections, both in adults and in children. Results showed that about 30% of the study participants were parasitaemic at day 3. Parasite clearance rate was estimated at 6.2h, which was comparable to figures from Pailin, Cambodia, where artemisinin resistance were previously reported . However, results from this study have to be interpreted bearing in mind that: (i) the age-based drug dosing scheme used has been criticized as insufficient to clear parasites and (ii) DHA-PPQ drugs used (Artecan™), Vietnam, are not produced under Good Manufacturing Practices (GMPs). However, those results prompted the NMCP and WHO to declare Quang Nam, Binh Phuoc, Dak Nong, and Gia Lai provinces as a "Tier I area" (credible evidence of artemisinin resistance) in May 2013. By end of 2014 a fifth province, Khanh Hoa, was declared Tier I (Dr Hong, Personal Communication). Except for the south-eastern province of Binh Phuoc, artemisinin resistance has never been confirmed with an artemisinin based monotherapy in Central Vietnam.
Therefore, in order to confirm artemisinin resistance in Central Vietnam , a study with oral artemisinin-based monotherapy, using WHO prequalified AS and DHA-PPQ and recommended dosing scheme of 4mg/kg/day for AS and DHA, is needed. In the arm where study participants are treated with 3 days of AS monotherapy, treatment will be followed by an additional 3-day course of DHA-PPQ to effectively clear all parasites.
The aim of the present study is to confirm artemisinin resistance in Central Vietnam by assessing P. falciparum clearance time and rate after AS monotherapy (WHO recommended dosage). The investigators will conduct a two-arm open label, randomized study, with one arm receiving AS monotherapy for 3 days + 3-day of DHA-PPQ, and a second arm receiving 3 days of DHA-PPQ.
详细描述
3.1 Study Design This study is designed as a randomized open label 42-day follow-up study to evaluate the clinical and parasitological responses after treatment of uncomplicated P.falciparum infections with either AS or DHA-PPQ. Symptomatic patients with P.falciparum mono-infections, fulfilling the study criteria, will be enrolled into the study, randomized to one of the treatment arms and followed up for 42 days. All drug administration 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 carrying gametocytes will be treated with a single dose of Primaquine (0.75mg/kg) following national guidelines.
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 incidences are the highest in the country. The study will be located in Chu R'Cam commune where the study team will be working together with the local health staff and all surrounding communes health centers with malaria patients.
The local population is mainly composed by the Gia Rai ethnic minority whose main occupations 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 an 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. falciparum infected patients either presenting spontaneously to the CHC or being referred by the health staff of the surrounding CHCs.
3.5. Trial procedures 3.5.1 Screening. 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 and 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
- Randomized
- 干预模型
- Parallel
- 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 with P. falciparum;
- •Parasite density (trophozoites) between 500-100,000/µl;
- •Fever (axillary temperature 37.5C) or history of fever in the previous 24h.;
- •Ability to swallow oral medication;
- •Ability and willingness to comply with the study protocol and with the study visit schedule;
- •Written informed consent/assent to participate to the trial.
排除标准
- •Mixed or mono-infection with another Plasmodium species confirmed by microscopy;
- •General danger signs or symptoms of severe malaria according to WHO definitions;
- •Signs or symptoms of severe malnutrition (weight-for-age ≤ 3 standard deviations below the mean (NCHS/WHO normalized reference values));
- •Anaemia (Hb <7g/dl in adults (<5g/dl in children));
- •Pregnancy or lactation (urine test for β HCG);
- •Concomitant acute illness necessitating specific treatment (antibiotics);
- •Underlying chronic severe illness (e.g. cardiac, renal, hepatic diseases, HIV/AIDS);
- •Known hypersensitivity to any of the drugs being evaluated;
- •Regular use of medication that may interfere with antimalaria pharmacokinetics
研究组 & 干预措施
Artesunate (AS) group
P. falciparum infected patients randomly allocated to this arm will be treated with AS (50mg/tablet) 4 mg/kg body weight once daily for three days followed by DHA-PPQ (40mg of DHA +320mg of PPQ/tablet) once daily for three days.
干预措施: Artesunate (AS) group (Drug)
DHA - PPQ group
P. falciparum infected patients randomly allocated to this arm will be treated with the combination DHA-PPQ (40mg of DHA +320mg of PPQ/tablet) once daily for three days.
干预措施: DHA - PPQ group (Drug)
结局指标
主要结局
Median parasite clearance time after treatment with Artesunate or with DHA - PIP
时间窗: From time of first treatment dose (day0 hh-mm) until day and time of parasite clearance (=two consecutive blood samples are found negative for parasites) assessed up day 42
Median parasite clearance time (total hours) in both arms (by light microscopy (LM) and quantitative real time PCR (qPCR)) will be computed using the 12-hourly parasite density measurements from day0 till parasite clearance. Parasite clearance time (in hours) will be computed using the Parasite Clearance Estimator tool available online (http://www.wwarn.org/toolkit/data-management/parasite-clearance-estimator).
次要结局
- Number of patients with Adequate Clinical and Parasitological Response (ACPR) to DHA-PPQ for the treatment for uncomplicated P falciparum malaria infections in central Vietnam.(From day0 to day 42)