Efficacy and Safety of Artemether-lumefantrine for the Treatment of Uncomplicated Plasmodium Falciparum Malaria and Chloroquine for Plasmodium Vivax in the Philippines From 2013-2014
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 159
- 主要终点
- Early Treatment Failure (ETF)
研究概览
简要总结
An antimalarial drug efficacy trial was conducted for artemether-lumefantrine (AL) and chloroquine (CQ) in the three (3) municipalities (Bataraza, Brookes and Rizal) of Palawan. Study subjects are febrile individuals between > 6 months old and 59 years old with confirmed uncomplicated P. falciparum or P. vivax infections. Patients with P. falciparum was treated with Artemether-lumefantrine administered 3 days (Days 0, 1 and 2) according to body weight. Primaquine at 0.75 mg base/kg body weight single dose was given on Day 3. For Plasmodium vivax patients chloroquine were administered according to body weight at a total dose of 25 mg/kg over 3 days (10 mg/kg on Day 0; 10 mg/kg on Day 1 and 5 mg/kg on Day 2), and primaquine following the National Treatment Guidelines.
During the period that this report covers, 84 and 75 patients met the inclusion criteria for Pf and Pv respectively. Clinical and parasitological parameters were monitored over a 28-day follow-up period for both drugs.
The presence of only 1 Late Clinical Failure (LCF) of P. falciparum parasitemia out of 84 enrolled patients and 2 Late Parasitological Failure (LPF) of P. vivax patients out of 75 enrolled patients within the 28 days follow up suggest that both drugs are still efficacious.
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 as 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, 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 and that of P. vivax.
STUDY OBJECTIVES The general objective of this study is to assess the therapeutic efficacy and safety artemether-lumefantrine for the treatment of uncomplicated P. falciparum infections and of chloroquine for the treatment of P. vivax infections in Palawan province, the Philippines from 2013-2014.
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 measure the clinical and parasitological efficacy of Chloroquine among patients aged between > 6 months and 59 years old suffering from vivax malaria, by determining the proportion of patients with clinical and parasitological failure, 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) and P. vivax (≥250/ul)
- •Axillary temperature ≥37.5 °C or oral/rectal temperature of ≥38 °C;
- •Glucose-6-dehydrogenase (G6PD) test normal for vivax patients if available
- •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 female 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: Arthemeter-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)
Patients detected with Plasmodium vivax (Chloroquine)
Patients with mono-infection of Plasmodium falciparum with ≥ 250 per µl
干预措施: Chloroquine (Drug)
Patients detected with Plasmodium vivax (Chloroquine)
Patients with mono-infection of Plasmodium falciparum with ≥ 250 per µl
干预措施: Primaquine (Drug)
结局指标
主要结局
Early Treatment Failure (ETF)
时间窗: Day 1-3
The classification of treatment outcomes will be based on an assessment of the parasitological and clinical outcomes of antimalarial treatment according to the latest guidelines of WHO. Accordingly, all patients will be classified as having an Early Treatment Failure by microscopy results P without PCR correction * 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.
Late Parasitological Failure (LPF)
时间窗: day 7 to day 28
Patients with late parasitological failure without PCR correction: • 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.
Late Clinical Failure (LCF)
时间窗: Day 4-28
Patients with late clinical failure without PCR correction: * Development of danger signs or severe malaria on any day from day 4 to day 28 in the presence of parasitaemia, 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.
Adequate Clinical and Parasitological Response (ACPR)
时间窗: Day 0-28
Adequate Clinical and Parasitological Response (ACPR): 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
Principal Investigator, Head of Parasitology Department
Research Institute for Tropical Medicine, Philippines