Study to Compare the Triple ACT AL+AQ With the ACT AL in Cambodia and Vietnam

42-day Polymerase Chain Reaction Corrected Efficacy According to Site/Geographic Region

42-day polymerase chain reaction corrected efficacy defined as adequate clinical and parasitological response (ACPR) according to site/geographic region.

Time frame: 42 day

Parasite Clearance Half-life

Parasite clearance half-life assessed by microscopy as primary parameter to determine parasite clearance

Time frame: 42 day

Fever Clearance Time

The time taken for the tympanic temperature to fall below 37.5˚C and remain there for at least 24 hours

Time frame: 42 day

Number of Severe Adverse Events by Study Arm

All numerators in AE tables mean that the AE was reported as present according to the definitions defined in the US government DAIDS 2017 grading tables for reporting of adverse events. The AEs are reported without grading in this table, but are graded in the paper reporting this clinical trial. All Primary analyses are reported (also in the accepted manuscript) along with the secondary outcomes needed to support the primary analysis. Secondary outcomes not involving the randomised comparison will be updated when the analyses are available. Please note that analyses of these Secondary outcomes will take time.

Time frame: 42 days

Incidence of Adverse Events Concerning Markers of Hepatic or Renal Toxicity

Total bilirubin, Alanine transaminase, Aspartate transaminase, Alkaline phosphatase and creatinine will be measured

Time frame: 42 day

Incidence of Prolongation of the Corrected QT Interval

We record the number of events where the QT interval exceeds 500ms or increases by 60ms or greater.

Time frame: 28 day

Prolongation of the Corrected QT Interval

We record the number of events where the QT interval exceeds 500ms or increases by 60ms or greater. There were zero events of this at any time point in either study arm. So no further analyses are possible.

Time frame: Hour 4, Hour 24, Hour 28, Hour 48, Hour 52, Hour 60, Hour 64, Day 7 and Day 28 and between these time points

Parasite Reduction Rates

Parasite reduction rates and ratios at 24 and 48 hours assessed by microscopy The data are collected, but this secondary outcome will come from analyses done by specialist researchers and the results will not affect the the presently reported primary outcomes of efficacy, safety and tolerability. These fields will be updated once results become available. We will also provide a link to the paper reporting the trial when it is published online as this will provide additional detail about the study.

Time frame: 24 and 48 hours

Parasite Count to Fall 50%

Time for parasite count to fall 50% of initial parasite density The data are collected, but this secondary outcome will come from analyses done by specialist researchers and the results will not affect the the presently reported primary outcomes of efficacy, safety and tolerability. These fields will be updated once results become available. We will also provide a link to the paper reporting the trial when it is published online as this will provide additional detail about the study.

Time frame: 42 days

Parasite Count to Fall 90%

Time for parasite count to fall 90% of initial parasite density The data are collected, but this secondary outcome will come from analyses done by specialist researchers and the results will not affect the the presently reported primary outcomes of efficacy, safety and tolerability. These fields will be updated once results become available. We will also provide a link to the paper reporting the trial when it is published online as this will provide additional detail about the study.

Time frame: 42 days

Parasite Count to Fall 99%

Time for parasite count to fall 99% of initial parasite density The data are collected, but this secondary outcome will come from analyses done by specialist researchers and the results will not affect the the presently reported primary outcomes of efficacy, safety and tolerability. These fields will be updated once results become available. We will also provide a link to the paper reporting the trial when it is published online as this will provide additional detail about the study.

Time frame: 42 days

Change in Haematocrit

Change in haematocrit at specified time points according to geographical location and study arm, stratified for G6PD status The data are collected, but this secondary outcome will come from analyses done by specialist researchers and the results will not affect the the presently reported primary outcomes of efficacy, safety and tolerability. These fields will be updated once results become available. We will also provide a link to the paper reporting the trial when it is published online as this will provide additional detail about the study.

Time frame: Day 1 to 7, 14, 21, 28, 35, 42

Correlation Between the Host Genotype and the Pharmacokinetics and Pharmacodynamics of Antimalarials

Correlation between the host genotype and the pharmacokinetics and pharmacodynamics of antimalarials The data are collected, but this secondary outcome will come from analyses done by specialist researchers and the results will not affect the the presently reported primary outcomes of efficacy, safety and tolerability. These fields will be updated once results become available. We will also provide a link to the paper reporting the trial when it is published online as this will provide additional detail about the study.

Time frame: 42 day

Proportion of Patients That Reports Completing a Full Course of Observed TACT or ACT

Proportion of patients that reports completing a full course of observed TACT or ACT without withdrawal of consent or exclusion from study because of drug related serious adverse event The data are collected, but this secondary outcome will come from analyses done by specialist researchers and the results will not affect the the presently reported primary outcomes of efficacy, safety and tolerability. These fields will be updated once results become available. We will also provide a link to the paper reporting the trial when it is published online as this will provide additional detail about the study.

Time frame: 42 day

Prevalence of Kelch13 Mutations of Known Significance

Prevalence of Kelch13 mutations of known significance The data are collected, but this secondary outcome will come from analyses done by specialist researchers and the results will not affect the the presently reported primary outcomes of efficacy, safety and tolerability. These fields will be updated once results become available. We will also provide a link to the paper reporting the trial when it is published online as this will provide additional detail about the study.

Time frame: 42 day

Prevalence/Incidence of Other Genetic Markers of Antimalarial Drug Resistance Such as Multidrug Resistance Gene 1 Copy Number and Multidrug Resistance Gene 1 Mutations

Prevalence/incidence of other genetic markers of antimalarial drug resistance such as multidrug resistance gene 1 copy number and multidrug resistance gene 1 mutations The data are collected, but this secondary outcome will come from analyses done by specialist researchers and the results will not affect the the presently reported primary outcomes of efficacy, safety and tolerability. These fields will be updated once results become available. We will also provide a link to the paper reporting the trial when it is published online as this will provide additional detail about the study.

Time frame: 48 hours

Genome Wide Association With in Vivo/in Vitro Sensitivity Parasite Phenotype

Genome wide association with in vivo/in vitro sensitivity parasite phenotype The data are collected, but this secondary outcome will come from analyses done by specialist researchers and the results will not affect the the presently reported primary outcomes of efficacy, safety and tolerability. These fields will be updated once results become available. We will also provide a link to the paper reporting the trial when it is published online as this will provide additional detail about the study.

Time frame: 42 day

Correlation Between Single Nucleotide Polymorphisms and Whole Genome Sequencing

Correlation between single nucleotide polymorphisms measured in dry blood spots and whole genome sequencing in leukocyte depleted blood samples The data are collected, but this secondary outcome will come from analyses done by specialist researchers and the results will not affect the the presently reported primary outcomes of efficacy, safety and tolerability. These fields will be updated once results become available. We will also provide a link to the paper reporting the trial when it is published online as this will provide additional detail about the study.

Time frame: 42 day

A Comparison of Transcriptomic Patterns Between Sensitive and Resistant Parasites

Transcriptomic patterns measure at baseline and at specified time points after the start of treatment comparing sensitive and resistant parasites. The data are collected, but this secondary outcome will come from analyses done by specialist researchers and the results will not affect the the presently reported primary outcomes of efficacy, safety and tolerability. These fields will be updated once results become available. We will also provide a link to the paper reporting the trial when it is published online as this will provide additional detail about the study.

Time frame: baseline and t = 6 hours

Correlation Between Quantitative Polymerase Chain Reaction Based Versus Microscopy Based Assessments of Parasite Clearance Dynamics

Correlation between qPCR based versus microscopy based assessments of parasite clearance dynamics The data are collected, but this secondary outcome will come from analyses done by specialist researchers and the results will not affect the the presently reported primary outcomes of efficacy, safety and tolerability. These fields will be updated once results become available. We will also provide a link to the paper reporting the trial when it is published online as this will provide additional detail about the study.

Time frame: 14 days

Proportion of Patients With Gametocytaemia Before, During and After Treatment With TACT or ACT

Proportion of patients with gametocytaemia before, during and after treatment with TACT or ACT stratified by the presence of gametocytes at enrolment The data are collected, but this secondary outcome will come from analyses done by specialist researchers and the results will not affect the the presently reported primary outcomes of efficacy, safety and tolerability. These fields will be updated once results become available. We will also provide a link to the paper reporting the trial when it is published online as this will provide additional detail about the study.

Time frame: At admission and up to day 14

Levels of RNA Transcription Coding for Male or Female Specific Gametocytes

Levels of RNA transcription coding for male or female specific gametocytes at admission up to day 14, stratified by the presence of gametocytes at enrolment The data are collected, but this secondary outcome will come from analyses done by specialist researchers and the results will not affect the the presently reported primary outcomes of efficacy, safety and tolerability. These fields will be updated once results become available. We will also provide a link to the paper reporting the trial when it is published online as this will provide additional detail about the study.

Time frame: 14 days

In Vitro Sensitivity of P. Falciparum to Artemisinins and Partner Drugs

In vitro sensitivity of P. falciparum to artemisinins and partner drugs according to study sites and genotype The data are collected, but this secondary outcome will come from analyses done by specialist researchers and the results will not affect the the presently reported primary outcomes of efficacy, safety and tolerability. These fields will be updated once results become available. We will also provide a link to the paper reporting the trial when it is published online as this will provide additional detail about the study.

Time frame: At admission & subjects with recurrent parasitaemia, up to 42 days

Pharmacokinetic Profiles and Interactions (Cmax) of Artemisinin-derivatives and Partner Drugs

Pharmacokinetic profiles and interactions (Cmax) of artemisinin-derivatives and partner drugs in 20 ACT treated and 20 TACT treated patients of both study arms in Vietnam The data are collected, but this secondary outcome will come from analyses done by specialist researchers and the results will not affect the the presently reported primary outcomes of efficacy, safety and tolerability. These fields will be updated once results become available. We will also provide a link to the paper reporting the trial when it is published online as this will provide additional detail about the study.

Time frame: 42 days

Pharmacokinetic Profiles and Interactions (AUC) of Artemisinin-derivatives and Partner Drugs

Pharmacokinetic profiles and interactions (AUC) of artemisinin-derivatives and partner drugs in 20 ACT treated and 20 TACT treated patients of both study arms in Vietnam The data are collected, but this secondary outcome will come from analyses done by specialist researchers and the results will not affect the the presently reported primary outcomes of efficacy, safety and tolerability. These fields will be updated once results become available. We will also provide a link to the paper reporting the trial when it is published online as this will provide additional detail about the study.

Time frame: 42 days

Day 7 Drug Levels of Partner Drugs in Association With Treatment Efficacy and Treatment Arm

Day 7 drug levels of partner drugs in association with treatment efficacy and treatment arm The data are collected, but this secondary outcome will come from analyses done by specialist researchers and the results will not affect the the presently reported primary outcomes of efficacy, safety and tolerability. These fields will be updated once results become available. We will also provide a link to the paper reporting the trial when it is published online as this will provide additional detail about the study.

Time frame: 7 days

Correlation Between Histidine-rich Protein 2 (HRP2) Based Versus Microscopy Based Assessments of Parasite Clearance Dynamics

Correlation between histidine-rich protein 2 (HRP2) based versus microscopy based assessments of parasite clearance dynamics The data are collected, but this secondary outcome will come from analyses done by specialist researchers and the results will not affect the the presently reported primary outcomes of efficacy, safety and tolerability. These fields will be updated once results become available. We will also provide a link to the paper reporting the trial when it is published online as this will provide additional detail about the study.

Time frame: 42 days