Phase 3
Completed N=310
Study to Compare the Triple ACT AL+AQ With the ACT AL in Cambodia and Vietnam
Malaria, Falciparum
Source: ClinicalTrials.gov NCT03355664 ↗
Enrolled (actual)
310
Serious AEs
2.3%
Results posted
Jul 2022
Primary outcomePrimary: Polymerase Chain Reaction Corrected Efficacy Defined as Adequate Clinical and Parasitological Response (ACPR) by Study Arm — 146; 151 Participants — p=0.38
◆ Published Evidence
Established
83citations · ~21 / year
Triple therapy with artemether-lumefantrine plus amodiaquine versus artemether-lumefantrine alone for artemisinin-resistant, uncomplicated falciparum malaria: an open-label, randomised, multicentre trial.
Summary
This study is a multi-centre, open-label randomised trial to assess the efficacy, safety and tolerability of the Triple ACT artemether-lumefantrine+amodiaquine (AL+AQ) compared to the ACT artemether-lumefantrine (AL) in uncomplicated falciparum malaria in Cambodia and Vietnam. The estimated total sample size is 600 patients from 2 sites in Cambodia and 2 sites in Vietnam. There are 2 treatment arms Arm 1: Artemether-lumefantrine for 3 days Arm 2: Artemether-lumefantrine for 3 days plus Amodiaquine for 3 days. According to the World Health Organization guideline, all patients except children under 10 kilograms will also be treated with a single dose of primaquine as a gametocytocidal treatment.
Funder :Bill & Melinda Gates Foundation (BMGF) Grant reference number: OPP1132628
Linked Publications
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Triple therapy with artemether-lumefantrine plus amodiaquine versus artemether-lumefantrine alone for artemisinin-resistant, uncomplicated falciparum malaria: an open-label, randomised, multicentre trial.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Polymerase Chain Reaction Corrected Efficacy Defined as Adequate Clinical and Parasitological Response (ACPR) by Study Arm |
146; 151 | 0.38 |
| SECONDARY 42-day Polymerase Chain Reaction Corrected Efficacy According to Site/Geographic Region |
32; 35; 91; 90; 23; 26 | — |
| SECONDARY Parasite Clearance Half-life |
5; 5.5 | — |
| SECONDARY Fever Clearance Time |
18.3; 14.9 | — |
| SECONDARY Number of Severe Adverse Events by Study Arm |
2; 5 | — |
| SECONDARY Incidence of Adverse Events Concerning Markers of Hepatic or Renal Toxicity |
53; 63 | — |
| SECONDARY Incidence of Prolongation of the Corrected QT Interval |
0; 0 | — |
| SECONDARY Prolongation of the Corrected QT Interval |
0; 0 | — |
| SECONDARY Parasite Reduction Rates |
— | — |
| SECONDARY Parasite Count to Fall 50% |
— | — |
| SECONDARY Parasite Count to Fall 90% |
— | — |
| SECONDARY Parasite Count to Fall 99% |
— | — |
| SECONDARY Change in Haematocrit |
— | — |
| SECONDARY Correlation Between the Host Genotype and the Pharmacokinetics and Pharmacodynamics of Antimalarials |
— | — |
| SECONDARY Proportion of Patients That Reports Completing a Full Course of Observed TACT or ACT |
— | — |
| SECONDARY Prevalence of Kelch13 Mutations of Known Significance |
— | — |
| SECONDARY Prevalence/Incidence of Other Genetic Markers of Antimalarial Drug Resistance Such as Multidrug Resistance Gene 1 Copy Number and Multidrug Resistance Gene 1 Mutations |
— | — |
| SECONDARY Genome Wide Association With in Vivo/in Vitro Sensitivity Parasite Phenotype |
— | — |
| SECONDARY Correlation Between Single Nucleotide Polymorphisms and Whole Genome Sequencing |
— | — |
| SECONDARY A Comparison of Transcriptomic Patterns Between Sensitive and Resistant Parasites |
— | — |
| SECONDARY Correlation Between Quantitative Polymerase Chain Reaction Based Versus Microscopy Based Assessments of Parasite Clearance Dynamics |
— | — |
| SECONDARY Proportion of Patients With Gametocytaemia Before, During and After Treatment With TACT or ACT |
— | — |
| SECONDARY Levels of RNA Transcription Coding for Male or Female Specific Gametocytes |
— | — |
| SECONDARY In Vitro Sensitivity of P. Falciparum to Artemisinins and Partner Drugs |
— | — |
| SECONDARY Pharmacokinetic Profiles and Interactions (Cmax) of Artemisinin-derivatives and Partner Drugs |
— | — |
| SECONDARY Pharmacokinetic Profiles and Interactions (AUC) of Artemisinin-derivatives and Partner Drugs |
— | — |
| SECONDARY Day 7 Drug Levels of Partner Drugs in Association With Treatment Efficacy and Treatment Arm |
— | — |
| SECONDARY Correlation Between Histidine-rich Protein 2 (HRP2) Based Versus Microscopy Based Assessments of Parasite Clearance Dynamics |
— | — |
Eligibility Criteria
Inclusion Criteria
- Male or female, aged from 2 years to 65 years old
- Acute uncomplicated P. falciparum malaria, confirmed by positive blood smear with asexual forms of P. falciparum (or mixed with non-falciparum species)
- Asexual P. falciparum parasitaemia: 16 to 200,000/microlitre, determined on a thin or thick blood film
- Fever defined as > 37.5°C tympanic temperature or a history of fever within the last 24 hours
- Written informed consent (by parent/guardian in case of children)
- Willingness and ability of the patients or parents/guardians to comply with the study protocol for the duration of the study
Exclusion Criteria
- Signs of severe/complicated malaria
- Haematocrit 450 milliseconds at moment of presentation
- Documented or claimed history of cardiac conduction problems
- Previous participation in the current study or another study in the previous 3 months
Data sourced from ClinicalTrials.gov (NCT03355664) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.