Triple Artemisinin-based Combination Therapy for Delaying Drug Resistance Development - a Randomized Clinical Trial
NCT ID: NCT05764746
Last Updated: 2024-12-11
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
RECRUITING
PHASE2/PHASE3
384 participants
INTERVENTIONAL
2023-05-01
2024-12-30
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
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.
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Keywords
Explore important study keywords that can help with search, categorization, and topic discovery.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
RANDOMIZED
PARALLEL
TREATMENT
DOUBLE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Artemether-lumefantrine followed by artesunate amodiaquine
a standard 3-days dosage, twice a day course of Artemether-Lumefantrine (20/120mg) immediately followed by a standard 3-days, once a day course of Artesunate-Amodiaquine (40base)
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
Artemether-lumefantrine with Amodiaquine
a standard 3-days dosage of Artemether-Lumefantrine (20/120mg) given together with Amodiaquine hydrocloride(40 base) followed by placebo for another 3 days;
Artemether-lumefantrine and Amodiaquine Drug Combination
AL and AQ will be given together for three days then followed by placebo for three days
Artemether-Lumefantrine alone
a standard 3-days dosage of Artemether-Lumefantrine (20/120mg) followed by placebo for another 3 days
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
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Artemether-lumefantrine and Amodiaquine Drug Combination
AL and AQ will be given together for three days then followed by placebo for three days
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
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
Other Intervention Names
Discover alternative or legacy names that may be used to describe the listed interventions across different sources.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* Weight ≥ 5 kg
* Body temperature ≥37.5°C or history of fever in the last 24 hours
* Microscopy confirmed P. falciparum mono-infection
* Parasitemia level of 1000-200000/μL
* Ability to swallow oral medication
* Ability and willingness to abide by the study protocol and the stipulated follow-up visits
* A written proxy informed consent from a parent/guardian
Exclusion Criteria
* Evidence of severe malaria or danger signs
* Known allergy to trial medicines
* Reported antimalarial intake ≤2 weeks
* Haemoglobin \<5 g/dL
* Blood transfusion within last 90 days
* Febrile condition other than malaria
* Known underlying chronic or severe disease (including severe malnutrition).
6 Months
120 Months
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
The Swedish Research Council
OTHER_GOV
Uppsala University
OTHER
Muhimbili University of Health and Allied Sciences
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Billy Ngasala
Associate Professor
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Billy E Ngasala, PhD
Role: PRINCIPAL_INVESTIGATOR
Muhimbili University of Health and Allied Sciences
Andreas Mårtensson, PhD
Role: PRINCIPAL_INVESTIGATOR
Muhimbili University of Health and Allied Sciences
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Kibindu
Bagamoyo, Dar esSalaam, Tanzania
Yombo Dispensary
Bagamoyo, Yombo, Tanzania
Countries
Review the countries where the study has at least one active or historical site.
Central Contacts
Reach out to these primary contacts for questions about participation or study logistics.
Facility Contacts
Find local site contact details for specific facilities participating in the trial.
Lwidiko E Mhamilawa, PhD
Role: primary
Ramadhani Hemedi, MD
Role: backup
References
Explore related publications, articles, or registry entries linked to this study.
Coran AG, Tyler HB. Aortic dissection. A complication of translumbar aortography. Am J Surg. 1968 May;115(5):709-11. doi: 10.1016/0002-9610(68)90107-4. No abstract available.
Smit MR, Ochomo EO, Aljayyoussi G, Kwambai TK, Abong'o BO, Chen T, Bousema T, Slater HC, Waterhouse D, Bayoh NM, Gimnig JE, Samuels AM, Desai MR, Phillips-Howard PA, Kariuki SK, Wang D, Ward SA, Ter Kuile FO. Safety and mosquitocidal efficacy of high-dose ivermectin when co-administered with dihydroartemisinin-piperaquine in Kenyan adults with uncomplicated malaria (IVERMAL): a randomised, double-blind, placebo-controlled trial. Lancet Infect Dis. 2018 Jun;18(6):615-626. doi: 10.1016/S1473-3099(18)30163-4. Epub 2018 Mar 27.
Dondorp AM, Nosten F, Yi P, Das D, Phyo AP, Tarning J, Lwin KM, Ariey F, Hanpithakpong W, Lee SJ, Ringwald P, Silamut K, Imwong M, Chotivanich K, Lim P, Herdman T, An SS, Yeung S, Singhasivanon P, Day NP, Lindegardh N, Socheat D, White NJ. Artemisinin resistance in Plasmodium falciparum malaria. N Engl J Med. 2009 Jul 30;361(5):455-67. doi: 10.1056/NEJMoa0808859.
Leang R, Taylor WR, Bouth DM, Song L, Tarning J, Char MC, Kim S, Witkowski B, Duru V, Domergue A, Khim N, Ringwald P, Menard D. Evidence of Plasmodium falciparum Malaria Multidrug Resistance to Artemisinin and Piperaquine in Western Cambodia: Dihydroartemisinin-Piperaquine Open-Label Multicenter Clinical Assessment. Antimicrob Agents Chemother. 2015 Aug;59(8):4719-26. doi: 10.1128/AAC.00835-15. Epub 2015 May 26.
Mwaiswelo R, Ngasala B, Gil JP, Malmberg M, Jovel I, Xu W, Premji Z, Mmbando BP, Bjorkman A, Martensson A. Sustained High Cure Rate of Artemether-Lumefantrine against Uncomplicated Plasmodium falciparum Malaria after 8 Years of Its Wide-Scale Use in Bagamoyo District, Tanzania. Am J Trop Med Hyg. 2017 Aug;97(2):526-532. doi: 10.4269/ajtmh.16-0780.
Mwaiswelo R, Ngasala B, Jovel I, Xu W, Larsson E, Malmberg M, Gil JP, Premji Z, Mmbando BP, Martensson A. Prevalence of and Risk Factors Associated with Polymerase Chain Reaction-Determined Plasmodium falciparum Positivity on Day 3 after Initiation of Artemether-Lumefantrine Treatment for Uncomplicated Malaria in Bagamoyo District, Tanzania. Am J Trop Med Hyg. 2019 May;100(5):1179-1186. doi: 10.4269/ajtmh.18-0729.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
3ACT-2023
Identifier Type: -
Identifier Source: org_study_id