NCT05764746

Triple Artemisinin-based Combination Therapy for Delaying Drug Resistance Development - a Randomized Clinical Trial

Can Triple Artemisinin-based Combination Therapy for Treatment of Uncomplicated Plasmodium Falciparum Malaria, Delay Drug Resistance Development of Plasmodium Falciparum in Tanzania: a Randomized Three Arm Clinical Trial

• Status: Recruiting
• Phase: Phase 2 / Phase 3
• Study type: Interventional
• Enrollment: 384 (estimated)
• Sponsor: Muhimbili University of Health and Allied Sciences · Academic / Other
• Sex: All
• Age: 6 Months – 120 Months
• Healthy volunteers: Not accepted

Summary

Background: Artemisinin resistance has emerged in parts of Southeast Asia, and there are reports in Africa of reduced susceptibility of Plasmodium falciparum parasites against artemisinin-based combination therapy (ACT). No new drugs are available in the pipeline to replace ACTs in case they fail. This study aims to assess whether a sequential administration of triple ACTs with different partner-drugs can improve the efficacy of ACT for treatment of uncomplicated malaria. Methods: A health facility-based, three-arm partially blinded randomized clinical trial will be conducted to assess efficacy and safety of a sequential administration of artemether-lumefantrine followed immediately by artesunate-amodiaquine (AL+ASAQ) or artemether-lumefantrine with by amodiaquine (AL+AQ) compared to artemether-lumefantrine plus placebo (AL+PBO). Eligible children aged 6 - 120 months and with microscopy confirmed uncomplicated P. falciparum malaria will be enrolled, administered with trial medicines and followed-up at 0 (just prior to first drug intake) and 8 hours on day 0, 12 hourly on days 1, 2, 3, 4, 5, followed by once daily on days 6, 7, 8, 9, 10, 11, 12, 13, 14, 21, 28, 35, 42 and 56 for clinical and laboratory evaluations. Clinical evaluation will involve assessment of signs and symptoms related to the disease and or trial medicine during follow-up. Laboratory evaluation will include microscopic determination of presence of malaria parasites and species, hemoglobin level, molecular analysis for markers of drug resistance and to differentiate recrudescence from new infection. The primary outcome will be Polymerase Chain Reaction (PCR)-adjusted adequate clinical and parasitological cure rate on days 28 and 42. Expected outcomes: The findings will give an insight on whether 3 ACTs are more efficacious than the use of first-line regimen alone, and are tolerable for treatment of uncomplicated falciparum malaria.

Conditions

• Uncomplicated Plasmodium Falciparum Malaria

Interventions

Type	Name	Description
DRUG	Artemether-lumefantrine and Amodiaquine Drug Combination	AL and AQ will be given together for three days then followed by placebo for three days
DRUG	Artemether-lumefantrine then Artesunate amodiaquine	AL will be given twice a day for three days then followed by artesunate amodiaquine once a day for three days
DRUG	Artemether-lumefantrine	This will be the comparator arm as standard treatment, where only AL will be given twice a day for three days then placebo for three days

Timeline

• Start date: 2023-05-01
• Primary completion: 2024-12-30
• Completion: 2024-12-30
• First posted: 2023-03-13
• Last updated: 2024-12-11

Locations

2 sites across 1 country: Tanzania