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.
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. Study sites: District Hospital Guider and District Hospital Figuil in the North Region of Cameroon. Study period: 11th April to 31st December 2022. Study design: This surveillance study is a two-arm, open-label, randomized controlled clinical trial. Patient population: Febrile patients aged 6 months to 10 years, with confirmed uncomplicated P. falciparum infection. 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 1:1. Sample size: A minimum sample of 76 patients will be required for the study. With a 20 % increase to allow for loss to follow-up and withdrawals during the 28-days and 42-days follow-up period, 92 patients will be enrolled for each of the two study arms. The study will recruit a total of 184 patients. At least 46 participants shall be enrolled into each drug arm of at the two sites. Treatment (s) and follow-up: 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 (AL), 35 and 42 (DHA-PPQ) 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. Classification of treatment outcomes: Classification of treatment outcomes will be done based on the WHO 2009 guidelines: treatment failure (Early Treatment Failure-ETF, Late Clinical failure-LCF and Late Parasitological Failure-LPF) and treatment success (Adequate Clinical and Parasitological Response-ACPR).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
184
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 1 blister of 12 tablets. It will be administered each day as two, four, six or eight tablets depending on the weight of the child.
Dihydroartemisinin-piperaquine is a 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 1 blister of 6 tablets. It will be given each day as a half, one, two or three tablets depending on the weight of the child.
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.
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.
Time frame: 10 months
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.
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. Recrudescence will be distinguished from re-infection by polymerase chain reaction (PCR) analysis.
Time frame: 10 months
The number of participants with treatment-related adverse events as assessed by CTCAE v4.0.
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.
Time frame: 10 months
The number of children with single nucleotide polymorphisms of P. falciparum genes responsible for resistance to AL and DHA-PPQ.
Pre-treatment and recrudescence/reinfection samples during follow-up shall be used to characterize the molecular markers of Plasmodium falciparum chloroquine resistant transporter(Pfcrt), Plasmodium falciparum multi-drug resistant 1 (Pfmdr1), and Plasmodium falciparum K13 (Pfk13) propeller domain conferring resistance to artemisinins or partner drugs.
Time frame: 10 months
The number of children with single nucleotide polymorphisms of P. falciparum histidine-rich protein 2 and 3 genes.
Pre-treatment shall be used to detect single nucleotide polymorphisms present in Plasmodium falciparum histidine-rich protein 2 and 3 genes.
Time frame: 10 months
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