Efficacy and Safety of Artemether-lumefantrine for the Treatment of Uncomplicated Plasmodium Falciparum Malaria in the Philippines in 2015
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 82
- 主要终点
- Number of Patients with Early Treatment Failure (ETF)
研究概览
简要总结
Artemether-lumefantrine has been used as a first-line treatment for uncomplicated Plasmodium falciparum infection since 2009 in the Philippines. The 28 day therapeutic efficacy study was conducted between February 2015 and December 2015, in accordance with WHO guidelines in the three (3) municipalities (Bataraza, Brookes and Rizal) of Palawan. Attempt was made to include Panglima-Sugala, Tawi-Tawi; however, due to the decline in the number of malaria cases, no evaluable subject was enrolled. The study subjects were febrile individuals between > 6 months old and 59 years old with confirmed uncomplicated P. falciparum. They were treated with artemether-lumefantrine (20 mg and 120 mg, respectively) administered 3 days (Days 0, 1 and 2) according to body weight. Primaquine (0.75 mg base/kg body weight single dose) was given on Day 3. Outcomes were classified as early treatment failure (ETF), late clinical failure (LCF), late parasitological failure (LPF) and adequate clinical and parasitological response (ACPR).
详细描述
In 2002, the Philippines changed its antimalarial drug policy to the combination treatment, CQ+SP as 1st-line treatment and artemether-lumefantrine as 2nd-line treatment. The DOH prescribed the use of artemether-lumefantrine (AL) combination as the second-line drug, limiting its use only in the treatment of confirmed Plasmodium falciparum until a further study on its efficacy was done before making it the first-line treatment. Consequently, AL became the first-line drug for falciparum malaria in the 2009 revised drug policy. The DOH in the past 6 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.
In the 2009 drug policy, chloroquine (CQ) remains the primary treatment for P. vivax malaria, with primaquine as an anti-relapse drug. Previous studies (1999-2005) elsewhere in the country have shown 100% efficacy of CQ or the CQ+PQ combination. However, in 2011, a recurrence of parasitemia was observed in one of 117 enrolled patients in Palawan. The last TES of AL as a first-line drug of choice for falciparum malaria was made in 2007. This study will update this drug's efficacy for this parasite.
STUDY OBJECTIVES The general objective of this study is to assess the therapeutic efficacy and safety of artemether-lumefantrine for the treatment of uncomplicated P. falciparum infections in Palawan province, the Philippines in 2015.
The specific objectives are:
- To measure the clinical and parasitological efficacy of artemether-lumefantrine (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 with an Adequate Clinical and Parasitological Response (ACPR) as indicators of efficacy;
- To evaluate the incidence of adverse events;
- To formulate recommendations to enable the Department of Health to make informed decisions about the possible need for updating of the current national antimalarial treatment guidelines.
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; and
- •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 an 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 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 to day 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.
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.
次要结局
未报告次要终点
研究者
Fe Espino
Medical Specialist IV / Head of Parasitology Department / Principal Investigator
Research Institute for Tropical Medicine, Philippines