CClinicalTrials.gg
CompletedNCT06300970Updated May 7, 2024

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

A Phase 4 interventional study of Amodiaquine-artesunate (ASAQ) and Artemether+Lumefantrine (AL) in Plasmodium Falciparum, Malaria and Uncomplicated Malaria, sponsored by Centers for Disease Control and Prevention. Completed at 2 sites in Liberia. Open to participants aged 6 Months to 59 Months. Per ClinicalTrials.gov, last updated 2024-05-07.

Sponsored by Centers for Disease Control and Prevention · Phase 4, Interventional, and Treatment

Phase
Phase 4
Study type
Interventional
Enrollment
352
Allocation
Non-randomized
Ages
6 Months to 59 Months
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Plasmodium Falciparum
  • Malaria
  • Uncomplicated Malaria

Keywords

  • Plasmodium falciparum
  • Anti-malarial therapeutic efficacy study (TES)
  • Artemisinin-based combination therapies (ACT)
03

Who can participate

Ages eligible
6 Months to 59 Months
Sexes eligible
All
Accepts healthy volunteers
No

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

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
04

Study design

Phase
Phase 4
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
352 participants (actual)

Study arms

  • 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)

  • 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)

Interventions

  • DrugAmodiaquine-artesunate (ASAQ)

    Oral medication given for treatment of uncomplicated plasmodium falciparum infection.

    Also known as: ASAQ, Camoquin

  • DrugArtemether+Lumefantrine (AL)

    Oral medication given for treatment of uncomplicated plasmodium falciparum infection.

    Also known as: AL, Coartem

05

What researchers measure

Primary outcomes

  1. 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

    Time frame: Day 1 to day 3 following treatment.

  2. 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

    Time frame: Day 4 to day 28 following treatment.

  3. 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.

    Time frame: Day 28 following treatment.

Secondary outcomes

  1. 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.

    Time frame: During participation in the study, approximately 4 weeks.

Other outcomes

  1. 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.

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

  2. 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.

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

06

Study locations

2 sites
  • 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
07

References and documents

Individual participant data

Plan to share: Yes — IPD should be requested from the Liberian Ministry of Health

Supporting information: Study protocol, Sap, Icf, Csr, Analytic code

No publications or documents are linked to this record.

08

Registry details

Key details

Study ID
NCT06300970
Lead sponsor
Centers for Disease Control and Prevention
Collaborators
Ministry of Health, Liberia
Responsible party
Jonathan Schultz (Medical Officer, Centers for Disease Control and Prevention) — Principal investigator
First posted
Mar 8, 2024
Start date
Aug 9, 2022
Primary completion
Aug 16, 2023
Completion
Aug 16, 2023
Last update
May 7, 2024

Study contacts

Victor S Koko
principal investigator · Liberia National Malaria Control Program

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in May 2024. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Start the discussion