A Multicentre Randomised Comparative Clinical Trial of the Efficacy of Artesunate + Amodiaquine Versus Artemether-lumefantrine (Coartem®) for the Treatment of Uncomplicated Childhood Plasmodium Falciparum Malaria in Zanzibar
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 359
- 主要终点
- PCR adjusted parasitological cure rates by day 42
研究概览
简要总结
The primary objective of the study was to determine the PCR-APCR up to day 42 in children <60 months of age, weighing ≥5kg with uncomplicated malaria, treated with either artesunate+ amodiaquine (ASAQ) or artemether-lumefantrine (AL; Coartem®).
Secondary objectives included: clinical and laboratory assessment of drug tolerability and safety, evaluation of possible correlation between drug bioavailability and clinical outcome, comparison of efficacy data with the pre-implementation "ACO I" study, parasite and fever clearance, gametocyte carriage, and possible selection of mutations related to quinoline resistance.
详细描述
All children in the right age group presenting with clinical signs of malaria at the study site were considered possible study subjects. The guardians of these children were informed about the study orally in Swahili according to the informed consent form. Those who were not willing to participate in the study were treated according to local standard procedure.
On day 0 the patient was tested for parasites using light microscopy on Giemsa stained blood films. A detailed clinical history and a clinical examination including an axillary temperature was assessed. Haemoglobin was assessed and blood samples were collected on filter paper for each child for genotyping of the parasites as well as for possible determination of blood levels of different antimalarial drugs.
The guardian was asked to bring their child back to the study site on day 1, 2, 3, 7, 14, 21, 28, 35 and 42. If they failed to do so they were visited in their homes to assure proper follow-up. At each follow-up the investigator asked about concomitant medication and adverse events, carefully filling out the clinical report form (CRF).
If, during the follow-up between day 14 and 42, a child previously enrolled in the study presented with fever, all tests and examinations were run as on day 0. If the child was clinically and parasitologically diagnosed with malaria again, he was treated as a new infection. If diagnosed with severe malaria during the follow-up period the patient was given rescue treatment (oral or intravenous Quinine) and withdrawn from the study. Each time an enrolled child presented at the site the CRF was completed with regards to clinical and laboratory status, treatment given and possible adverse events.
Clinical and laboratory assessments included:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 主要目的
- Treatment
- 盲法
- None
盲法说明
No blinding was done due to the different drug formulations and regimens.
入排标准
- 年龄范围
- — 至 60 Months（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Weight ≥5kg
- •No general danger signs or severe malaria present (see 4.4.2.1 & 4.4.2.2)
- •History of fever within 24 hours OR axillary temperature ≥ 37.5Cº
- •No other cause of fever is detectable
- •No severe malnutrition
- •Patient has parasite counts between 2000-200,000/ul (50-5000/200 white blood cells)
- •Guardian/Patient has understood the procedures of the study and is willing to participate
- •Patient able to come for stipulated follow up visits and has easy access to the Study Site
排除标准
- •General Danger Signs and Complications:
- •Not able to drink or breastfeed
- •Vomiting everything
- •Recent history of convulsions
- •Lethargic or unconscious
- •Unable to sit or stand (as appropriate for age)
- •History of allergy to test drugs
- •History of intake of any drugs other than paracetamol and aspirin within 3 days
- •Signs of Severe Malaria:
- •Altered consciousness
- •Repeated convulsions
- •Inability of oral intake
- •Severe anaemia (Hb <5gm/dl)
- •Difficulty in breathing (pulmonary oedema, Respiratory Distress Syndrome)
- •Shock (small pulse, cold extremities)
- •Hypoglycaemia
- •Haemoglobinuria (dark coloured urine or Coca-Cola urine)
- •Kidney failure (little or no urine in a well-hydrated patient)
- •Jaundice (yellow colouring of eyes)
- •Hyperpyrexia (temperature above 39.5ºC) in combination with other signs
- •Hyperparasitaemia (more than 5% red blood cells parasitized or >200,000 parasites/µl)
- •Spontaneous bleeding (Disseminated Intravascular Coagulation)
研究组 & 干预措施
Treatment with artesunate + amodiaquine
Co-administration of a daily dose of artesunate (Arsumax) 4mg/kg and amodiaquine (Flavoquine) 10mg/kg for 3 days, under direct observation. Children <12months <10kg: artesunate (Arsumax) 50mg - 0.5tab/day + amodiaquine (Flavoquine) 153mg - 0.5tab/day; Children 12-59months 10-20kg: artesunate (Arsumax) 50mg - 1 tab/day + amodiaquine (Flavoquine) 153mg 1 tab/day.
干预措施: Artesunate + Amodiaquine (Drug)
Treatment with artemether-lumefantrine (Coartem®)
Artemether-lumefantrine (Coartem®) - artemether 1.3mg/kg + lumefantrine 4mg/kg administered twice daily, both doses under direct observation either in the clinic or in the patient's home. Children <60 months, 5-14kg: 1 tab/dose; Children <60 months >14kg: 2 tabs/dose.
干预措施: Artemether-lumefantrine (Drug)
结局指标
主要结局
PCR adjusted parasitological cure rates by day 42
时间窗: 42 days
Comparing PCR adjusted parasitological cure rate (PCR-APCR) between the two treatment options up to day 42. Parasitological cure will be adjusted using PCR genotyping of msp2 marker. Recrudescence is defined as the presence of at least one matching allelic band, and reinfection as the absence of any matching allelic band on day 0 and day of recurring parasitaemia. Patients with recurrent parasitaemia having missing filter paper sample or negative PCR results will be considered uncertain with regards to PCR adjusted outcome.
次要结局
- The clinical and parasitological response outcome (i.e. cure rates) on days 14, day 28 and 42.(42 days)
研究者
Professor Anders Björkman
Professor
Karolinska Institutet