Efficacy of Artesunate-amodiaquine and Artemether-lumefantrine for Treatment of Plasmodium Falciparum Malaria in Liberia

Phase 4

Completed

• Conditions: Malaria; Plasmodium Falciparum; Uncomplicated Malaria
• Interventions: Drug: Amodiaquine-artesunate (ASAQ); Drug: Artemether+Lumefantrine (AL)

• Registration Number: NCT06300970
• Lead Sponsor: Centers for Disease Control and Prevention

Brief Summary

To assess the efficacy of both first-line antimalarial medications used for the treatment of uncomplicated Plasmodium falciparum malaria infections in two geographic regions in Liberia.

Detailed Description

Title: Efficacy of artesunate+amodiaquine (ASAQ) and artemether+lumefantrine (AL) for the treatment of uncomplicated Plasmodium falciparum malaria in Liberia

Objective: To assess the efficacy of both first-line ASAQ and AL for the treatment of uncomplicated P. falciparum malaria infections

Study Sites: Sacleapea Comprehensive Health Center, Saclepea-Mah District in Nimba County; and Sinje Health Center, Garwula District, Sinje, in Grand Cape Mount County

Study Period: August 2022 to August 2023

Study Design: Prospective study of two cohorts with simultaneous enrolment of each therapy

Patient population: Patients aged 6 to 59 months with confirmed uncomplicated P. falciparum infection

Sample Size: Total number of patients to be enrolled is 352 patients. This consists of 88 patients per arm per site. There are two arms in each of the two sites.

Treatment(s) and follow-up: Patients enrolled in the ASAQ arm will receive the treatment once daily dose for three days. Patients enrolled in the AL arm will receive treatment twice daily dose for three days. Clinical and parasitological parameters will be monitored over a 28-day follow-up period to evaluate drug 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 will be recorded.

Exploratory endpoints: Any polymorphisms of molecular markers for antimalarial drug resistance and prevalence of HRP2 deletions.

Study Timeline

• Study Start: 2022-08-09
• Primary Completion: 2023-08-16
• Study Completion: 2023-08-16
• Study First Submitted: 2024-02-13
• Study First Submitted QC: 2024-03-07
• Study First Posted: 2024-03-08
• Status Verified: 2024-05
• Last Update Submitted: 2024-05-06
• Last Update Posted: 2024-05-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 352

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Artesunate+Amodiaquine (ASAQ)	Amodiaquine-artesunate (ASAQ)	Amodiaquine-artesunate (ASAQ) dose based on weight, given once daily for three days. ASAQ has three formulations, with the dose depending on the weight of the child according to the following. 4.5-8.9 kg = 1 tablet 25 mg AS/67.5 mg AQ 9-17.9kg = 1 tablet 50 mg AS/135 mg AQ 18.0-35.9kg = 1 tablet 100 mg AS/270 mg AQ ≥36.0kg = 2 tablets 100 mg AS/270 mg AQ
Artemether+Lumefantrine (AL)	Artemether+Lumefantrine (AL)	Artemether+Lumefantrine (AL) dose is based on weight and given twice daily for three days. AL has one formulation, with pills containing 20 mg artemether and 120 mg lumefantrine. The number of tablets per dose depends on the weight of the child according to the following: 5 -14.9 kg = 1 tablet per dose 15 -24.9 kg = 2 tablets per dose 25 -34.9 kg = 3 tablets per dose ≥35 kg = 4 tablets per dose 1 tablet contains 20 mg artemether and 120 mg lumefantrine

Primary Outcome Measures

Name	Time	Method
Number of Participants with Late Treatment Failure (LTF)	Day 4 to day 28 following treatment.	* Danger signs, signs of severe malaria, or axillary temperature \> 37.5 °C in the presence of parasitemia on any day between day 4 and day 28 in patients who did not previously meet any of the criteria of early treatment failure; * Presence of parasitemia (with a parasite with the same genotype as day 0) on any day between day 7 and day 28 regardless of temperature in patients who did not previously meet any of the criteria of early treatment failure
Number of Participants with Adequate Clinical and Parasitological Response (APCR)	Day 28 following treatment.	• Absence of parasitemia on day 28, irrespective of axillary temperature, in patients who did not previously meet any of the criteria of early treatment failure, late clinical failure, reinfection or late parasitological failure.
Number of Participants with Early Treatment Failure (ETF)	Day 1 to day 3 following treatment.	* Danger signs or severe malaria on day 1, 2, or 3 in the presence of parasitemia; * A parasitemia on day 2 higher than day 0; * Axillary temperature ≥ 37.5 °C on day 3 in the presence of parasitemia; * Parasitemia on day 3 ≥ 25% of day 0 parasitemia

Secondary Outcome Measures

Name	Time	Method
Number of Patients with Adverse Events	During participation in the study, approximately 4 weeks.	An adverse event is defined as any unfavorable, unintended sign, symptom, syndrome or disease that develops or worsens with the use of a medicinal product, regardless of whether it is related to the medicinal product during participation in the study, approximately 4 weeks.

Trial Locations

Locations (2)

Sinje Health Center, Garwula District, Sinje, Grand Cape Mount County; 🇱🇷 Sinje, Grand Cape Mount County, Liberia

Saclepea-Mahn Comprehensive Health Center Saclepea-Mahn District, Nimba County; 🇱🇷 Saclepea, Nimba County, Liberia