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

NCT06300970 | Completed Phase 4

• 1 other identifier: 0900f3eb81e634a9
• Study Type: interventional
• Target: 352
• Locations: 1 country
• Sites: 2

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.

Conditions

Plasmodium Falciparum; Malaria; Uncomplicated Malaria

Keywords

Plasmodium falciparum; Anti-malarial therapeutic efficacy study (TES); Artemisinin-based combination therapies (ACT)

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (1)

• Number of Patients with Adverse Events

  During participation in the study, approximately 4 weeks.

Other Outcomes (2)

• Number of samples with confirmed Histidine-rich protein 2/3 (HRP2/3) gene deletions

  Samples collected from participants during the study, approximately 4 weeks.

• Number of samples with molecular markers of anti-malarial resistance

  Samples collected from participants during the study, approximately 4 weeks.

Study Arms (2)

Artesunate+Amodiaquine (ASAQ)

ACTIVE COMPARATOR

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)

Artemether+Lumefantrine (AL)

ACTIVE COMPARATOR

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)

Interventions

Amodiaquine-artesunate (ASAQ) DRUG

Oral medication given for treatment of uncomplicated plasmodium falciparum infection.

Also known as: ASAQ, Camoquin

Artesunate+Amodiaquine (ASAQ)

Artemether+Lumefantrine (AL) DRUG

Oral medication given for treatment of uncomplicated plasmodium falciparum infection.

Also known as: AL, Coartem

Artemether+Lumefantrine (AL)

Eligibility Criteria

• Age: 6 Months - 59 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Centers for Disease Control and Prevention: lead
• Ministry of Health, Liberia: collaborator

Study Sites (2)

Sinje Health Center, Garwula District, Sinje, Grand Cape Mount County

Sinje, Grand Cape Mount County, Liberia

Location

Saclepea-Mahn Comprehensive Health Center Saclepea-Mahn District, Nimba County

Saclepea, Nimba, Liberia

Location

MeSH Terms

Conditions

Malaria, Falciparum; Malaria

Interventions

amodiaquine, artesunate drug combination; Amodiaquine; Artemether, Lumefantrine Drug Combination

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Intervention Hierarchy (Ancestors)

Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Artemether; Artemisinins; Reactive Oxygen Species; Free Radicals; Inorganic Chemicals; Organic Chemicals; Lumefantrine; Fluorenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sesquiterpenes; Terpenes; Polycyclic Compounds; Drug Combinations; Pharmaceutical Preparations

Study Officials

• Victor S Koko

  Liberia National Malaria Control Program

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Officer

Study Record Dates

• First Submitted: February 13, 2024
• First Posted: March 8, 2024
• Study Start: August 9, 2022
• Primary Completion: August 16, 2023
• Study Completion: August 16, 2023
• Last Updated: May 7, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Supporting information and data can be requested from the Liberian Ministry of Health.
• Access Criteria: Supporting information and data can be requested from the Liberian Ministry of Health.

Locations

LI (2)