Efficacy and Safety of Artemether-Lumefantrine and Dihydroartemisinin-Piperaquine for the Treatment of Uncomplicated Plasmodium Falciparum Malaria Among Children in the North Region of Cameroon
试验速览
- 阶段
- 4 期
- 发起方
- 入组人数
- 184
- 主要终点
- The number of participants with treatment success and adverse events following treatment with AL and DHA-PPQ in children infected with uncomplicated P. falciparum malaria.
研究概览
简要总结
Malaria is an infectious disease transmitted by the bite of an infected female anopheles mosquito. The most vulnerable group that bears the highest disease burden includes children less than five years and pregnant women. Artemether-lumefantrine (AL) has been used for the treatment of uncomplicated Plasmodium falciparum in Cameroon since 2006. In 2020, the government of Cameroon also adopted the use of dihydroartemisinin-piperaquine (DHA-PPQ) as one of the first line drugs for the treatment of malaria. Globally, several studies among children have reported high efficacy and safety of artemisinin-based combination therapies (ACTs). However, there is paucity of data to support the continuous use of AL and DHA-PPQ in Cameroon. The main objective of this study is to assess the efficacy and safety of artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DHA-PPQ) uncomplicated P. falciparum malaria in the North Region of Cameroon. A randomized, open-label, controlled clinical trial comparing artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DHA-PPQ) will be carried out from 11th April to 31st December, 2022 at two hospitals in the North Region of Cameroon. The study participants shall include febrile patients aged 6 months to 10 years with confirmed uncomplicated P. falciparum infection. Eligible children for whom parent/guardian assents are obtained will be randomized to receive either artemether-lumefantrine (group A) or dihydroartemisinin-piperaquine (group B) in the ratio 1:1. A minimum sample of 76 patients will be required for the study. With a 20 % increase to allow loss to follow-up and withdrawals during the 28-days (AL) or 42-days (DHA-PPQ) follow-up period, 92 patients will be enrolled into each of the two study arms. The study will recruit a total of 184 patients. However, since 2 study sites will be involved, a minimum of 92 (46 per drug arm) participants shall be enrolled per site. Drug intake will be done under strict supervision on days 0, 1 and 2. Follow-up visits will be performed on days 3, 7, 14, 21, 28, 35 and 42 to evaluate clinical and parasitological resolution of their malaria episode as well as adverse events. Polymerase chain reaction (PCR) of Plasmodium falciparum merozoite surface proteins 1 and 2 (Pfmsp1, Pfmsp2), glutamate-rich protein (Pfglurp) and microsatellites will be used to differentiate between recrudescence and new infection.
详细描述
Brief title: Efficacy and Safety of Artemether-Lumefantrine (AL) and Dihydroartemisinin-Piperaquine (DHA-PPQ) in Cameroon
Official title: Efficacy and Safety of Artemether-Lumefantrine and Dihydroartemisinin-Piperaquine for the treatment of uncomplicated Plasmodium falciparum malaria among children in the North Region of Cameroon
Purpose: To assess the efficacy and safety of artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DHA-PPQ) for the treatment of uncomplicated P. falciparum malaria among children 6 to 120 months at District Hospital Figuil and District Hospital Guider in the North Region of Cameroon.
Background: Malaria is an infectious disease transmitted by the bite of an infected female anopheles mosquito. The most vulnerable group includes children less than five years and pregnant women. artemether-lumefantrine (AL) has been used for the treatment of uncomplicated Plasmodium falciparum in Cameroon since 2006. In 2020, the government of Cameroon also adopted the use of dihydroartemisinin-piperaquine (DHA-PPQ) as one of the first line drugs for the treatment of malaria. Globally, several studies among children have reported high efficacy and safety of artemisinin-based combination therapies (ACTs). However, there is paucity of data to support the continuous use of AL and DHA-PPQ in Cameroon.
Objective: To assess the efficacy and safety of artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DHA-PPQ) for the treatment of uncomplicated P. falciparum malaria among children 6 to 120 months at District Hospital Figuil and District Hospital Guider in the North Region of Cameroon.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 6 Months 至 120 Months（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Children of either gender, aged 6 months to 10 years will be recruited.
- •Uncomplicated P. falciparum malaria confirmed by microscopy using Giemsa-stained thick film with an asexual parasite density within the range of 1000 to 200000 parasites/μl.
- •Presenting with fever (axillary temperature ≥ 37.5 ºC) or having a history of fever in the preceding 24 hours.
- •Able to ingest tablets orally (either suspended in water or uncrushed with food).
- •Willing to participate in the study with written informed consent from parent/guardian.
- •Willing and able to attend the clinic on stipulated regular follow-up visits.
排除标准
- •Mixed or mono-infection with another Plasmodium species detected by microscopy.
- •Children who are currently suffering or had the following within the last 2 months: tuberculosis, HIV, schistosomiasis, diabetes mellitus, cardiovascular disease, gout, rheumatoid arthritis, underlying chronic hepatic or renal disease, hypoglycemia, jaundice, respiratory distress, and other inflammatory-related diseases.
- •Signs/symptoms indicating severe/complicated malaria" according to WHO criteria (WHO definition) such as:
- •Not able to drink or breastfeed.
- •Persistent vomiting (>2 episodes within the previous 24 hours).
- •Convulsions (>1 episode within the previous 24 hours).
- •Lethargic/unconscious.
- •Severe anemia (hemoglobin < 5 g/dl).
- •Serious gastrointestinal disease.
- •Presence of severe malnutrition defined as a child aged between 6-60 months whose weight-for-height is below -3 z-score (W/H < 70%) or has symmetrical edema involving at least the feet or has a mid-upper arm circumference <115 mm).
- •Regular medication, which may interfere with antimalarial pharmacokinetics.
- •History of hypersensitivity reactions or contraindications to any of the medicine (s) being tested or used as alternative treatment (s).
- •Individuals who have taken part in anti-malarial efficacy and safety studies in the last 3 months.
- •Participants who have taken antimalarial drugs within the last one month.
研究组 & 干预措施
Artemether-lumefantrine
Drug: Artemether-lumefantrine drug combination Artemether-lumefantrine is formulated as tablets and will be provided in blister packs. Each tablet contains 20 mg artemether and 120 mg lumefantrine. Every pack has a picture showing how the drug should be given and contains a blister of 12 tablets. It will be administered each day as one, two or three tablets depending on the weight of the child.
干预措施: Artemether-Lumefantrine Drug Combination (Drug)
Dihydroartemisinin-piperaquine
Drug: Dihydroartemisinin-piperaquine drug combination Dihydroartemisinin-piperaquine is formulated as tablets and will be provided in blister packs. Each tablet contains 40 mg dihydroartemisinin and 320 mg piperaquine. Every pack has a picture showing how the drug should be given and contains a blister of 6 tablets and given each day as half, one, two or three tablets depending on the weight of the child.
干预措施: Dihydroartemisinin-Piperaquine drug combination (Drug)
结局指标
主要结局
The number of participants with treatment success and adverse events following treatment with AL and DHA-PPQ in children infected with uncomplicated P. falciparum malaria.
时间窗: 10 months
Eligible children for whom parent/guardian informed consents are obtained will be randomized to receive either artemether-lumefantrine (group A) or dihydroartemisinin-piperaquine (group B) in the ratio of 1:1.
次要结局
- The proportion of patients with early treatment failure, late clinical failure, late parasitological failure or an adequate clinical and parasitological response as indicators of efficacy according to the WHO 2009 guidelines.(10 months)
- The number of children with single nucleotide polymorphisms of P. falciparum genes responsible for resistance to AL and DHA-PPQ.(10 months)
- The number of children with single nucleotide polymorphisms of P. falciparum histidine-rich protein 2 and 3 genes.(10 months)
- The number of participants with treatment-related adverse events as assessed by CTCAE v4.0.(10 months)
研究者
Professor Wilfred Fon Mbacham
Principal Investigator, Professor of Public Health Biotechnology
University of Yaounde 1