Clinical trial NCT04767191: Malaria Therapeutic Efficacy Study (TES) Kenya
Official title: Efficacy of Artemether Lumefantrine (AL) and Dihydroartemisinin-Piperaquine (DHP) for the Treatment of Uncomplicated Plasmodium Falciparum Malaria in Siaya and Bungoma Counties, Kenya
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Uncomplicated Malaria
Lead sponsor: Jhpiego
Sponsor class: OTHER
Collaborators: name: Kenya Ministry of Health
name: Centers for Disease Control and Prevention
name: United States Agency for International Development (USAID)
First posted: 2021-02-23
Enrollment: 400
Sex: ALL
Minimum age (years): 6
Maximum age (years): 59
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The two drugs being assessed are already approved and in use by the Kenya Ministry of Health as the 1st and 2nd line treatments for malaria. The study is to assess the continued efficacy of the drugs.
Primary purpose: TREATMENT

Brief summary: WHO recommends that Therapeutic Efficacy Studies (TES) for 1st and 2nd line antimalarial medicines should be routinely carried out and data made available for decision-making due to the threat of emergence and spread of artemisinin resistance in malaria-endemic countries, especially in Africa. In line with this WHO recommendation, Kenya Ministry of Health (MOH) is conducting the TES to determine the efficacy of artemether lumefantrine (AL), and dihydroartemisinin-piperaquine (DHP), the first and second line treatment of uncomplicated malaria in Kenya. The objective of this study is to inform the decisions or actions made by a public health authority (Kenya Ministry of Health) to inform decision on revision of the antimalarial guidelines and policy in Kenya. Jhpiego's Impact Malaria project in Kenya, with funding and technical oversight from US President's Malaria Initiative (PMI) through USAID and CDC, will support the Kenya MOH in its effort to evaluate the efficacy of AL and DHP in the treatment of children with uncomplicated malaria. The study is being conducted by Kenya MOH, with technical support and funding by PMI-USAID through Jhpiego in Kenya.

Detailed description: WHO recommends that Therapeutic Efficacy Studies (TES) for 1st and 2nd line antimalarial medicines should be routinely carried out and data made available for decision-making due to the threat of emergence and spread of artemisinin resistance in malaria-endemic countries, especially in Africa. In its strategy to strengthen malaria surveillance, Kenya's Ministry of Health (MOH) National Malaria Program (NMP) planned to conduct TES every three years to ascertain continuing efficacy of the first and second-line treatments. The last TES for 1st line treatment of malaria in Kenya was done in Siaya county in 2016. In line with the WHO recommendation, Jhpiego Impact Malaria project in Kenya, with funding and technical oversight from Center for Disease Prevention and Control (CDC) will be supporting the Kenya MOH NMP to conduct a TES to assess the efficacy of the current first and second line treatment policy in Kenya. The study is being conducted by Kenya MOH NMP, with technical oversight and funding by CDC through the Jhpiego Impact Malaria project in Kenya.

Objective: To assess the efficacy of Artemether Lumefantrine (AL) and Dihydroartemisinin-Piperaquine (DHP) for the treatment of uncomplicated P. falciparum malaria infections.

Study Sites: One site will be selected in Siaya county and one site will be selected in Bungoma county (Kimilili Sub-County). Both sites will be Level-2 facilities (health centers) with high outpatient department attendance of patients with malaria. At each site, there will be two study arms: one arm for AL and one arm for DHP.

Study Period: March 2021 to September 2021

Study Design: This surveillance study is a two-arm prospective study Patient population: Febrile patients aged between 6 months and 59 months, with confirmed uncomplicated P. falciparum monoinfection.

Sample Size: At each site, at least 100 patients will be enrolled per drug (200 patients per site, 400 patients total).

Treatment(s) and follow-up: Clinical and parasitological parameters will be monitored over a 28-day follow-up period to evaluate AL efficacy, and over a 42-day follow-up period to evaluate DHP efficacy.

Primary endpoints: 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. Recrudescence will be distinguished from re-infection by polymerase chain reaction (PCR) analysis.

Secondary endpoints: The frequency and nature of adverse events.

Exploratory endpoints: to determine the polymorphism of molecular markers of drug resistance and evasion of diagnostic testing; to determine the blood concentration of AL

Eligibility criteria: Inclusion Criteria:

* age between 6 months to 59 months; mono-infection with P. falciparum confirmed by positive blood smear (i.e. no mixed infection);
* parasitaemia of 1,000 - 100,000/µl asexual forms;
* presence of axillary temperature ≥ 37.5 °C or history of fever during the past 24 h;
* ability to swallow oral medication;
* haemoglobin ≥5.0 g/dL at admission;
* informed consent from a parent or guardian;
* parent/guardian agrees to bring the patient for planned follow-up visits at day 7, 14, 21, and 28

Exclusion Criteria:

* general danger signs or signs of severe falciparum malaria according to the definitions of WHO;
* severe malnutrition according to WHO child growth standards (WHO, 2006), children with marasmus or oedematous malnutrition;
* mixed or mono-infection with another Plasmodium species detected by microscopy;
* presence of febrile conditions due to diseases other than malaria (e.g. measles, acute lower respiratory tract infection, severe diarrhea with dehydration) or other known underlying chronic or severe diseases (e.g. cardiac, renal and hepatic diseases, HIV/AIDS);
* 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);
* history of receiving any antimalarial treatment in the preceding 72 hours;. exposure to malaria vaccine

Primary outcomes:
measure: Number of patients (in the Artemether Lumefantrine arm) with clinical and parasitological cure (i.e. free of malaria symptoms and parasites) assessed clinically and via microscopy and rapid diagnostic test.
timeFrame: By day 28 post-treatment
measure: Number of patients (in the Dihydroartemisinin-Piperaquine arm) with clinical and parasitological cure (i.e. free of malaria symptoms and parasites) assessed clinically and via microscopy and rapid diagnostic test.
timeFrame: By day 42 post-treatment
Secondary outcomes:
measure: Number of patients (in the Artemether Lumefantrine arm arm) with treatment-related adverse events
timeFrame: by day 28 post-treatment
measure: Number of patients (in the Dihydroartemisinin-Piperaquine arm) with treatment-related adverse events
timeFrame: by day 42 post-treatment
measure: Number of patients (in the Artemether Lumefantrine arm) with molecular markers of drug resistance assessed via phenotype test
timeFrame: by day 28 post-treatment
measure: Number of patients (in the Dihydroartemisinin-Piperaquine arm) with molecular markers of drug resistance assessed via phenotype test
timeFrame: by day 42 post-treatment
Other outcomes:
Locations:
city: Bungoma
country: Kenya
facility: Makhonge Health Centre
state: Bungoma County
city: Siaya
country: Kenya
facility: Kaluo Health Centre
state: Siaya County
Study officials:
References: