Efficacy and Safety of Artemether-lumefantrine for the Treatment of Uncomplicated Plasmodium Falciparum Malaria in the Philippines in 2017-2018
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 80
- 主要终点
- Number of Patients with Early Treatment Failure (ETF)
研究概览
简要总结
The emergence and spread of drug resistance is a major obstacle to combating malaria. The World Health Organization (WHO) recommends that regular efficacy monitoring should be undertaken by all malaria endemic countries that have deployed artemisinin combination therapy (ACT), to help early detection of drug resistant strains of the parasite and contain their rapid spread. Artemether-lumefantrine (AL) has been the first-line antimalarial drug against uncomplicated Plasmodium falciparum malaria in the Philippines since 2009, with primaquine as an anti-relapse drug. The objective of this study is to assess the safety and efficacy of artemether-lumefantrine for the treatment of uncomplicated P. falciparum infections in the Philippines. The study was conducted in three (3) municipalities (Bataraza, Brooke's Point, and Rizal) of Palawan. Single-arm prospective study of a 28-day follow-up was conducted from February 2017 to December 2018 according to the revised WHO 2014 drug efficacy study protocol. Study subjects were consenting individuals seeking care at the selected Rural Health Units, who were aged >6 months old to 59 years old with confirmed uncomplicated P. falciparum infections. AL was administered for 3 days according to body weight (Days 0, 1 and 2) and primaquine 0.75 mg/kg body weight single dose was given on Day 3 following the National Treatment Guidelines.
详细描述
Early diagnosis and timely treatment of malaria with an effective drug is an important strategy to control malaria. However, antimalarial drug resistance is one of the major obstacles to controlling this disease. Following a widespread failure of chloroquine (CQ) and sulfadoxine-pyrimethamine (SP), most malaria-endemic countries had shifted their malaria treatment policy to artemisinin-based combination therapy (ACT). In the Philippines, AL became the first-line drug for falciparum malaria in the 2009 revised drug policy. The DOH in the past years (2002-2007) adopted the use of AL in the highly endemic areas of the country and conducted therapeutic efficacy studies (TES) in 3 sentinel sites: Kalinga-Isabela, Palawan and several Mindanao provinces, showing 97-100% efficacy. Whereas CQ+SP showed variability and declining efficacy, results ranged from 70%-95% (CARAGA region). In Sultan Kudarat province, results in 2006-2007 showed 90% efficacy of CQ+SP and 96% for AL for falciparum malaria. The last TES of AL as a first-line drug of choice for falciparum malaria was made in 2015 with 98.7% efficacy.
The results of this study will be used to assist the Department of Health of the Philippines in assessing the current national treatment guidelines for P. falciparum and updating the policy if necessary.
OBJECTIVES. The general objective of this study is to assess the therapeutic efficacy and safety of artemether-lumefantrine for treatment of chloroquine for the treatment of uncomplicated P. falciparum infections in the Philippines in 2017-2018.
The primary objectives are:
- To measure the clinical and parasitological efficacy of artemether-lumenfantrine (AL) among patients aged between > 6 months and 59 years old suffering from uncomplicated falciparum malaria, by determining the proportion of patients with Early Treatment Failure (ETF), Late Clinical Failure (LTF), Late Parasitological Failure (LPF), or an Adequate Clinical and Parasitological Response (ACPR) as indicators of efficacy;
- To differentiate recrudescences from new infections by the Polymerase Chain Reaction (PCR) analysis;
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 6 Months 至 59 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Above 6 months old to 59 years old;
- •Mono-infection with P. falciparum (1000-100 000 asexual forms per µl)
- •Axillary temperature ≥37.5 °C or oral/rectal temperature of ≥38 °C;
- •Ability to swallow medication;
- •Ability and willingness to comply with the study 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 legal guardian in the case of children less than 18 years old;
- •Informed assent from any minor participant aged 12 - 17 years;
- •Consent for pregnancy testing from females of child-bearing potential and from their parent or guardian if under 18 years old.
排除标准
- •Presence of general danger signs among children <5 years old or other signs of severe and complicated falciparum malaria according to current WHO definitions
- •Mixed Plasmodium species;
- •Presence of severe malnutrition
- •Presence of febrile conditions due to diseases other than malaria (measles, acute lower tract respiratory infection, severe diarrhea with dehydration, etc.), or other known underlying chronic or severe diseases (e.g. cardiac, renal, hepatic diseases, HIV/AIDS)
- •History of hypersensitivity reactions to any of the drug(s) being tested or used as alternative treatment.
研究组 & 干预措施
Patients detected with Plasmodium falciparum (Artemether-lumefantrine)
Patients with mono-infection of Plasmodium falciparum with 1,000-100,000 asexual forms per µl
干预措施: Artemether-lumefantrine (Drug)
Patients detected with Plasmodium falciparum (Artemether-lumefantrine)
Patients with mono-infection of Plasmodium falciparum with 1,000-100,000 asexual forms per µl
干预措施: Primaquine (Drug)
结局指标
主要结局
Number of Patients with Early Treatment Failure (ETF)
时间窗: Day 1-3
The number of patients with the following criteria based on microscopy results without PCR: * Development of danger signs or severe malaria on day 1, day 2, or day 3 in the presence of parasitemia; * Parasitaemia on day 2 higher than day 0 count irrespective of axillary temperature; * Parasitaemia on day 3 with axillary temperature ≥37.5 ºC; * Parasitaemia on day 3 ≥25% of count on day 0.
Number of Patients with Adequate Clinical and Parasitological Response (ACPR)
时间窗: Day 0-28
The number of patients with absence of parasitemia on day 28 irrespective of axillary temperature without previously meeting any of the criteria of Early Treatment Failure or Late Clinical Failure or Late Parasitological Failure.
Late Clinical Failure (LCF)
时间窗: Day 4-28
The number of patients with the following criteria based on microscopy results without PCR: * Development of danger signs or severe malaria on any day from day 4 to day 28 in the presence of parasitemia, without previously meeting any of the criteria of Early Treatment Failure; * Presence of parasitemia and axillary temperature ≥37.5 ºC (or history of fever in low/moderate transmission areas) on any day from day 4 to day 28, without previously meeting any of the criteria of Early Treatment Failure.
Number of Patients with Late Parasitological Failure (LPF)
时间窗: Day 7-28
The number of patients with the presence of parasitemia on any day from day 7 to day 28 and axillary temperature \<37.5 ºC, without previously meeting any of the criteria of Early Treatment Failure or Late Clinical Failure.
次要结局
未报告次要终点
研究者
Fe Espino
Medical Specialist IV, Principal Investigator, Head of Parasitology Department
Research Institute for Tropical Medicine, Philippines