Clinical trial NCT06300970: Efficacy of Artesunate-amodiaquine and Artemether-lumefantrine for Treatment of Plasmodium Falciparum Malaria in Liberia
Official title: Efficacy of Artesunate-amodiaquine (ASAQ) and Artemether-lumefantrine (AL) for the Treatment of Uncomplicated Plasmodium Falciparum Malaria in Liberia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Plasmodium Falciparum
Malaria
Uncomplicated Malaria
Keywords: Plasmodium falciparum
Anti-malarial therapeutic efficacy study (TES)
Artemisinin-based combination therapies (ACT)
Lead sponsor: Centers for Disease Control and Prevention
Sponsor class: FED
Collaborators: name: Ministry of Health, Liberia
First posted: 2024-03-08
Enrollment: 352
Sex: ALL
Minimum age (years): 6
Maximum age (years): 59
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants with Early Treatment Failure (ETF)
timeFrame: Day 1 to day 3 following treatment.
measure: Number of Participants with Late Treatment Failure (LTF)
timeFrame: Day 4 to day 28 following treatment.
measure: Number of Participants with Adequate Clinical and Parasitological Response (APCR)
timeFrame: Day 28 following treatment.
Secondary outcomes:
measure: Number of Patients with Adverse Events
timeFrame: During participation in the study, approximately 4 weeks.
Other outcomes:
measure: Number of samples with confirmed Histidine-rich protein 2/3 (HRP2/3) gene deletions
timeFrame: Samples collected from participants during the study, approximately 4 weeks.
measure: Number of samples with molecular markers of anti-malarial resistance
timeFrame: Samples collected from participants during the study, approximately 4 weeks.
Locations:
city: Sinje
country: Liberia
facility: Sinje Health Center, Garwula District, Sinje, Grand Cape Mount County
state: Grand Cape Mount County
city: Saclepea
country: Liberia
facility: Saclepea-Mahn Comprehensive Health Center Saclepea-Mahn District, Nimba County
state: Nimba County
Study officials:
affiliation: Liberia National Malaria Control Program
name: Victor S Koko
role: PRINCIPAL_INVESTIGATOR
References: