Assessment of in Vivo and in Vitro Efficacy of Combined Artesunate/Mefloquine Therapy for Treatment of Uncomplicated Plasmodium Falciparum Infection in the Peruvian Amazon
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 45
- 试验地点
- 1
- 主要终点
- Parasite clearance time
研究概览
简要总结
There is growing evidence of the emergence of P. falciparum resistance to artesunate (a derivative of artemisin) in Southeast Asia. The emergence and spread of resistant strains to artemisinin would represent an alarming threat to the success of the antimalarial combination therapy in the region. The delayed clearance of parasitemia for more than 24 hours has been taken as an early sign of resistance, a phenomenon seen at the Thai-Cambodia border.
The purpose of this research study, is to assess the in vitro and in vivo efficacy of combinated artesunate/mefloquine therapy to treatment of uncomplicated Plasmodium falciparum malaria in the Peruvian Amazon through the analysis of the rate of clearance of parasitemia and other important outcomes.
详细描述
Combination therapy with artemisinin derivatives is the treatment of choice for malaria by P. falciparum since 2006, but there is growing evidence of the emergence of P. falciparum resistance to artesunate in Southeast Asia. The delayed clearance of parasitemia for more than 24 hours has been taken as an early sign of resistance, a phenomenon seen at the Thai-Cambodia border. The emergence and spread of resistant strains to artemisinin would represent an alarming threat to the success of the antimalarial combination therapy in the region.
This research study, will be conducted in collaboration with the National Institute of Health of Peru.
Objectives:
Main Objective: To determine the rate of clearance of parasitemia in the first 72 hours after administration of artesunate.
Secondary/exploratory objectives:
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 5 Years 至 65 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age between 5 and 65 years old inclusive
- •Monoinfection of P. falciparum confirmed by microscopy
- •Documented fever (axillary temperature > 37.5°C) and/or history of fever during the previous 48 hours in the absence of other obvious causes of fever (such as pneumonia, otitis media, etc)
- •Infection with P. falciparum of 1000 and 100,000 asexual parasites per microliter (μl) to be determined by microscopic examination of a thick or thin smear, and positive confirmation by polymerase chain reaction (PCR); * Presence of sexual form of P. vivax is acceptable; ** PCR confirmation is not an enrollment requirement
- •Informed consent must be obtained from the participant or both parents/guardian (in the case of children), and assent from the child (from 8 to 17 years old)
- •Willingness of the participant to return to the health facility for regular check-ups during the follow-up period of 42 days
- •Willingness of the participant to transfer to the Hospital de Apoyo Iquitos to start treatment
排除标准
- •Severe malaria signs (as defined by the World Health Organization):
- •Cerebral malaria (irreversible coma)
- •Severe anemia (hematocrit < 15%, or clinic signs)
- •Clinic signs of kidney failure (e.g., serum creatinine > 3 mg/dL)
- •Pulmonary edema
- •Hypoglycemia (glucose in the blood <40mg/dL or clinic signs)
- •Shock (PA systolic < 70 mm Hg in adults; < 50 in children)
- •Spontaneous bleeding/Disseminated intravascular coagulation (CID)
- •Recurrent generalized convulsions
- •Acidemia/acidosis (clinic signs)
- •Macroscopic hemoglobinuria
- •Jaundice Laboratory tests for measuring some of these conditions may not be available at all study sites. If they are not, we will use clinical criteria of severe malaria at the discretion of the study physician
- •Background of other chronic or severe diseases (e.g., heart, kidney, liver diseases, HIV/AIDS, severe malnutrition), determined clinically by medical history and physical examination
- •Background of hypersensitivity to any of the drugs tested or used as an alternative treatment: AS, MQ, quinine or tetracycline/clindamycin
- •Gestation (based on a serum pregnancy test or medical history) or desire to become pregnant during the study period, or not using any family planning method while being sexually active (confirmed by urine pregnancy test)
- •Breastfeeding a child under 6 months old
- •Have received antimalarial drugs in the previous 7 days
- •Inability to eat or drink, vomiting (more than twice in the last 24 hours), recent history of seizures (one or more in the previous 24 hours), altered level of consciousness, inability to sit or stand
- •Splenectomy background
研究组 & 干预措施
Artesunate/mefloquine
Orally administration of artesunate 4mg/Kg by three days Orally administration of mefloquine 15mg/Kg in the fourth day Orally administration of mefloquine 10mg/Kg in the fifth day
干预措施: Artesunate (Drug)
Artesunate/mefloquine
Orally administration of artesunate 4mg/Kg by three days Orally administration of mefloquine 15mg/Kg in the fourth day Orally administration of mefloquine 10mg/Kg in the fifth day
干预措施: Mefloquine (Drug)
结局指标
主要结局
Parasite clearance time
时间窗: up to 72 hours after administration of artesunate
Parasite clearance time assessed by microscopy and quantitative PCR
次要结局
- Parasite reduction rates and ratios(24, 48 hours after the first administration of artesunate)
- Time for parasite count to fall(at least 24 hours)
- Fever clearance time(at least 24 hours)
- Gametocyte carriage rates(up to 14 days since the first administration of artesunate)