Clinical Efficacy of Artemisinin-based Combination Therapy for Treatment of Uncomplicated Plasmodium Falciparum Malaria in North Sumatera, Indonesia and the Association of Molecular Markers With Treatment Outcomes
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 338
- 试验地点
- 2
- 主要终点
- Efficacy of dihydroartemisinin-piperaquine and artemether-lumefantrine
研究概览
简要总结
This is a prospective, open label, randomised controlled trial to assess the safety and efficacy of dihydroartemisinin-piperaquine and artemether-lumefantrine in children and adults with uncomplicated Plasmodium falciparum malaria infection. Molecular markers for antimalarial resistance will also be assessed and the presence of molecular markers in the parasites will be associated with treatment outcomes.
详细描述
Artemisinin-based combination therapy (ACT) is the current recommended treatment by WHO for uncomplicated falciparum malaria. It is highly effective with few adverse effects. The artemisinin component is combined with a partner drug with a longer half-life to ensure the clearance of the remaining parasites after rapid reduction by artemisinin.
ACT is used as first-line treatment for uncomplicated P. falciparum infection in Indonesia since 2004. There are 3 combinations available in the country including artesunate-amodiaquine (AS-AQ), dihydroartemisinin-piperaquine (DHA-PQ) and artemether-lumefantrine (AL). Studies at different sites across Indonesia have shown various efficacy. Yet, there is an increased concern of reduced susceptibility of P. falciparum to artemisinin in neighbouring countries. Therefore, there is a need to evaluate and monitor the efficacies of these combinations in Indonesia.
Molecular markers are an important tool for detecting and monitoring the presence of antimalarial resistance. Their significant implication is to geographically map the extent of resistant-parasites, thus enabling strategies for their control and elimination to be applied before the inevitably increase in the disease burden occurs. Different markers have been used to identify antimalarial resistance and recently a molecular marker for artemisinin susceptibility in P. falciparum has also been proposed. The presence of these markers in parasites from our study will also be investigated.
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
- 6 Months 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female
- •All patients per 6 months of age
- •Fever as defined by axillary temperature > 37.5 C or history of fever during the 48 hours before recruitment
- •Infection with P. falciparum detected by microscopy
- •Parasitaemia > 250 /uL blood
- •Ability to swallow oral medication
- •Ability and willingness to comply with the protocol for the duration of the study and to comply with the study visit schedule
- •Informed consent from the patient or from a parent or guardian in the case of children
- •Absence of history to hypersensitive reactions or contraindication to antimalarial drugs
- •Not currently consuming antibiotic with antimalarial activity (such as cotrimoxazole, macrolides, tetracycline or doxycycline)
排除标准
- •Presence of general danger signs in children under 5 years or signs of severe falciparum malaria according to the definitions of WHO (2000)
- •Presence of severe malnutrition according to WHO child growth standards
- •Presence of febrile conditions caused by diseases other than malaria
- •Presence of severe anemia (Hemoglobin < 7 gr/dL)
- •Received any of the study drugs within the past 4 weeks
- •Received any antimalarial within the last 2 weeks
- •Recurrent vomiting )necessitating more than a single repeat dose)
- •Pregnant (demonstrated by positive result of b-HCG in women of childbearing age
- •Lactating mother
研究组 & 干预措施
DHA-PQ
One tablet of dihydroartemisinin-piperaquine consists of 40 mg of dihydroartemisinin and 320 mg of piperaquine. DHA-PQ is administered once daily for 3 days (at enrolment, hour 24 and you 48). Dosing should be given based on body weight. Daily dose for dihydroartemisinin is 2.25 mg/kg (total 6.75 mg/kg) and for piperaquine is 18 mg/kg (total 54 mg/kg).
干预措施: Dihydroartemisinin-Piperaquine (Drug)
AL
Half a tablet of artemether-lumefantrine consists of 20 mg of artemether and 120 mg of lumefantrine is given per 5 kg body weight. AL is administered as 6-dose regimens given twice daily for 3 days (at enrolment, hour 8, hour 24, hour 36, hour 48 and hour 60).
干预措施: Artemether-lumefantrine (Drug)
结局指标
主要结局
Efficacy of dihydroartemisinin-piperaquine and artemether-lumefantrine
时间窗: 42 days
Early treatment failure, late treatment failure, adequate clinical and parasitological response Proportion of participants with Adequate Clinical and Parasitological Response
次要结局
- Parasite clearance times(3 days)
- Fever clearance times(3 days)
- Prevalence of molecular markers and the impact on treatment outcomes(42 days)
- Prevalence of gametocyte(42 days)
- Presence of other Plasmodium species(42 days)
- Haematological recovery(28 days)