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

Efficacy of Artesunate-amodiaquine (ASAQ) and Artemether-lumefantrine (AL) for the Treatment of Uncomplicated Plasmodium Falciparum Malaria in Liberia

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.

Study Overview

• Status: Completed
• Conditions: Malaria; Plasmodium Falciparum; Uncomplicated Malaria
• Intervention / Treatment: Drug: Amodiaquine-artesunate (ASAQ); Drug: Artemether+Lumefantrine (AL)

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 Type: Interventional
• Enrollment (Actual): 352
• Phase: Phase 4

Contacts and Locations

Study Locations

• Liberia
  • Grand Cape Mount County
    • Sinje, Grand Cape Mount County, Liberia
      • Sinje Health Center, Garwula District, Sinje, Grand Cape Mount County
  • Nimba County
    • Saclepea, Nimba County, Liberia
      • Saclepea-Mahn Comprehensive Health Center Saclepea-Mahn District, Nimba County

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

1. Age between 6 to 59 months (5 years)
2. Weight ≥ 5 kg
3. Monoinfection with P. falciparum with a parasite density of 2,000 to 200,000 asexual forms per microliter of blood
4. Axillary temperature ≥37.5˚C or history of fever in the last 24 hours
5. Hemoglobin ≥ 8.0g/dl
6. Easy access to the health facility and ability to return to the health facility over the course of the four weeks of follow-up
7. Informed consent of parent or guardian

Exclusion Criteria on Day 0

1. Any danger signs or signs of severe malaria (see Appendix I)
2. Pneumonia or bronchopneumonia
3. Severe malnutrition (Z-score < 3)
4. History of taking antimalarials (or antibiotics with antimalarial activity such as cotrimoxazole, tetracycline or doxycycline) in the last 14 days
5. Mixed malaria infection
6. History of hypersensitivity or allergy to the medication

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Artesunate+Amodiaquine (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	Drug: Amodiaquine-artesunate (ASAQ); Oral medication given for treatment of uncomplicated plasmodium falciparum infection.; Other Names: ASAQ; Camoquin
Active Comparator: 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	Drug: Artemether+Lumefantrine (AL); Oral medication given for treatment of uncomplicated plasmodium falciparum infection.; Other Names: Coartem; AL

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Early Treatment Failure (ETF)	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	Day 1 to day 3 following treatment.
Number of Participants with Late Treatment Failure (LTF)	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	Day 4 to day 28 following treatment.
Number of Participants with Adequate Clinical and Parasitological Response (APCR)	• 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.	Day 28 following treatment.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Patients with Adverse Events	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.	During participation in the study, approximately 4 weeks.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of samples with confirmed Histidine-rich protein 2/3 (HRP2/3) gene deletions	Molecular data on hrp2/hrp3 deletions will be tabulated and frequencies will be calculated from samples collected during the study, approximately 4 weeks.	Samples collected from participants during the study, approximately 4 weeks.
Number of samples with molecular markers of anti-malarial resistance	Molecular data on drug resistance polymorphisms will be tabulated and frequencies will be calculated from samples collected during the study, approximately 4 weeks.	Samples collected from participants during the study, approximately 4 weeks.

Collaborators and Investigators

• Sponsor: Centers for Disease Control and Prevention
• Collaborators: Ministry of Health, Liberia
• Investigators: Principal Investigator: Victor S Koko, Liberia National Malaria Control Program

Study record dates

Study Major Dates

• Study Start (Actual): August 9, 2022
• Primary Completion (Actual): August 16, 2023
• Study Completion (Actual): August 16, 2023

Study Registration Dates

• First Submitted: February 13, 2024
• First Submitted That Met QC Criteria: March 7, 2024
• First Posted (Actual): March 8, 2024

Study Record Updates

• Last Update Posted (Actual): May 7, 2024
• Last Update Submitted That Met QC Criteria: May 6, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Plasmodium falciparum; Anti-malarial therapeutic efficacy study (TES); Artemisinin-based combination therapies (ACT)
• Additional Relevant MeSH Terms: Infections; Vector Borne Diseases; Parasitic Diseases; Protozoan Infections; Mosquito-Borne Diseases; Malaria; Malaria, Falciparum; Anti-Infective Agents; Antiviral Agents; Antineoplastic Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Anthelmintics; Schistosomicides; Antiplatyhelmintic Agents; Lumefantrine; Artemether; Artesunate; Artemether, Lumefantrine Drug Combination; Amodiaquine
• Other Study ID Numbers: 0900f3eb81e634a9

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD should be requested from the Liberian Ministry of Health
• IPD Sharing Time Frame: Supporting information and data can be requested from the Liberian Ministry of Health.
• IPD Sharing Access Criteria: Supporting information and data can be requested from the Liberian Ministry of Health.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No