Observational Study to Evaluate the Clinical Safety After Introduction of the Fixed Dose Artemisinin-based Combination Therapy Eurartesim® (Dihydroartemisinin/Piperaquine [Dha/Pqp]) in Public Health Districts in Sub-Saharan Africa.
试验速览
- 阶段
- 不适用
- 入组人数
- 10,000
- 试验地点
- 7
- 主要终点
- Adverse events
研究概览
简要总结
WHO recommends the use of artemisinin-based combination therapies (ACTs) in the treatment of uncomplicated malaria to stem falciparum malaria drug resistance. New ACTs are entering the African market and will be used by the public health care system. The collection of safety data and risk evaluation through observational data are critical in order to assess risk/benefit profile of each ACT through its life cycle and providing information on the best use. Additionally there is need to assess the impact of the introduction of a new ACT in the evolution of its efficacy and malaria morbidity and mortality. Dihydroartemisinin/Piperaquine (DHA/PQP) is a new ACT approved by European Medical Agency and a number of African countries. This is a phase IV observational evaluation of the clinical safety of the fixed-dose DHA/PQP (Eurartesim®) in public health facilities within selected Health and Demographic Surveillance Centres in Burkina Faso (Nouna), Mozambique (Manhica), Ghana (Dodowa, Kintampo, Navrongo), Tanzania (Rufiji) and other African countries to be added. Eurartesim® will be used as first-line treatment of uncomplicated malaria an objective to evaluate the safety of Eurartesim® when used under usual conditions in 10,000 patients. Patients > 6 months and 5 kg except pregnant women will be enrolled and Eurartesim® administered as a single daily dose regimen over 3 days. Patients will be contacted at Day 5 (± 2 days) after treatment, to assess recovery and any adverse events.
详细描述
Study will be performed in public health facilities in up to 7 selected HDSS centres (Health and Demographic Surveillance sites) within the HDSS in Burkina Faso (1), Mozambique (1), Ghana (3), and Tanzania (2), where Eurartesim® will be used as first-line treatment of uncomplicated malaria episodes.
Primary:
Evaluate the safety of Eurartesim® when used under usual conditions in 10,000 patients with signs and symptoms of uncomplicated malaria confirmed by a parasitological diagnosis (Microscopy/Rapid Diagnostic Test) or, when this test is not available, by WHO diagnostic criteria.
Main Secondary:
Intensive assessment of a nested subset of 1,000 patients to evaluate the effect of the administration of Eurartesim® on blood biochemistry, full blood count, WBC differential count and QTc intervals. QTc interval and piperaquine concentration relationship will also be investigated in selected centers.
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 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Uncomplicated malaria (Plasmodia of any species) diagnosed as per national policies and in line with WHO recommendations (a history of fever in the previous 24 h and/or the presence of anaemia, for which pallor of the palms appears to be the most reliable sign in young children). Confirmation of malaria by a parasitological diagnosis with RDT is encouraged but its absence does not prevent patients from being enrolled.
- •Age ≥ 6 months and weight ≥ 5 kg.
- •Capability of taking an oral medication.
- •Ability and willingness to participate based on signed informed consent (a parent or a guardian has to sign for children below 18 years old), or on verbal consent given in front of a witness signing the informed consent, and access to health facility. The patient is to comply with all scheduled follow-up visits.
排除标准
- •• Known allergy to artemisinin or to piperaquine.
- •Known pregnancy.
- •Lactating women should be excluded if other anti-malarial treatments are available
- •Complicated malaria.
- •Taking medicinal products that are known to prolong the QTc interval. These include (but are not limited to):
- •Antiarrhythmics (e.g. amiodarone, disopyramide, dofetilide, ibutilide, procainamide, quinidine, hydroquinidine, sotalol).
- •Neuroleptics (e.g. phenothiazines, sertindole, sultopride, chlorpromazine, haloperidol, mesoridazine, pimozide, or thioridazine), antidepressive agents.
- •Certain antimicrobial agents, including agents of the following classes:
- •macrolides (e.g. erythromycin, clarithromycin),
- •fluoroquinolones (e.g. moxifloxacin, sparfloxacin),
- •imidazole and triazole antifungal agents,
- •and also pentamidine and saquinavir.
- •Certain non-sedating antihistamines (e.g. terfenadine, astemizole, mizolastine).
- •Cisapride, droperidol, domperidone, bepridil, diphemanil, probucol, levomethadyl, methadone, vinca alkaloids, arsenic trioxide.
- •Have taken a DHA/PQP dose in the previous four weeks.
- •Family history of sudden unexplained death, or personal or family history of predisposing cardiac conditions for arrhythmia/QT prolongation (including congenital long QT syndrome, arrhythmia, QTc interval greater than 450 milliseconds with either Bazett or Fridericia correction).
研究组 & 干预措施
Dihydroartemisinin and piperaquine
The patients will take Eurartesim® (DHA/PQP) with a dose regimen of one administration every 24 hours over a period of three days, i.e. at Day 1, then after 24 hours (Day 2) and after 48 hours (Day 3) from the first administration. The dose will be based on body weight. Two strengths of Eurartesim® will be provided for dosing in children and adults: 20/160mg and 40/320mg of DHA and PQP respectively. Body weight (kg) Daily dose (mg) Number of tablets per dose 20/160mg DHA/PQ 40/320mg DHA/PQ 5 to <7 10 mg DHA and 80 mg PQP ½ tablet 7 to <13 20 mg DHA and 160 mg PQP 1 tablet 13 to < 24 40 mg DHA and 320 mg PQP 1 tablet 24 to < 36 80 mg DHA and 640 mg PQP 2 tablets 36 to < 75 120 mg DHA and 960 mg PQP 3 tablets 75 to < 100 160 mg DHA and 1280 mg PQP 4 tablets > 100.
干预措施: Dihydroartemisinin and piperaquine (Drug)
结局指标
主要结局
Adverse events
时间窗: 28 Days
• Clinical safety will be determined by analysis of the number of adverse events (frequency, intensity, action taken, outcome) captured during their follow up contacts on Day 5 (±2 days) after starting the treatment with Eurartesim® as well as those identified in the referring hospitals or through adverse events spontaneously reported by the patient detected at the health facility within 28 days after the first medication intake.
次要结局
- Adverse events of special interest(28 Days)