Trial Outcomes & Findings for Study to Compare the Triple ACT AL+AQ With the ACT AL in Cambodia and Vietnam (NCT NCT03355664)

NCT ID: NCT03355664

Last Updated: 2022-07-15

Results Overview

Efficacy is defined as participants, following initial parasite and fever clearance, not having a recrudescence of the original plasmodium infection and fever, up to 42 days of follow up.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 310 participants
• Primary outcome timeframe: 42 days
• Results posted on: 2022-07-15

Participant Flow

Enrolled at hospitals and health centres 18 March 2018 to 30 January 2020

Actual number randomised was 312, however, an exclusion criterion was an ECG-measured QTc interval of ≥450ms. After randomisation the ECG was routinely repeated before drug administration, and in 2 participants (1 in each arm) the repeat ECG was ≥450 therefore no study drug was administered and the participants were treated with standard of care and recovered fully. There is no further data on these participants and the denominator for all subsequent tables is the 310 who received study drugs.

Participant milestones

Measure	Artemether-lumefantrine for 3 Days Plus Primaquine at Hour 24 ACT: Artemether-lumefantrine (20/120 mg) as a fixed dose combination twice daily for 3 days according to weight plus low dose primaquine at hour 24	Artemether-lumefantrine for 3 Days Plus Amodiaquine for 3 Days Plus Primaquine at Hour 24 TACT: Artemether-lumefantrine (20/120 mg) as a fixed dose combination twice daily for 3 days according to weight plus Amodiaquine (150mg) twice daily for 3 days according to weight plus low dose primaquine at hour 24
Overall Study STARTED	154	156
Overall Study COMPLETED	139	144
Overall Study NOT COMPLETED	15	12

Reasons for withdrawal

Measure	Artemether-lumefantrine for 3 Days Plus Primaquine at Hour 24 ACT: Artemether-lumefantrine (20/120 mg) as a fixed dose combination twice daily for 3 days according to weight plus low dose primaquine at hour 24	Artemether-lumefantrine for 3 Days Plus Amodiaquine for 3 Days Plus Primaquine at Hour 24 TACT: Artemether-lumefantrine (20/120 mg) as a fixed dose combination twice daily for 3 days according to weight plus Amodiaquine (150mg) twice daily for 3 days according to weight plus low dose primaquine at hour 24
Overall Study Adverse Event	1	2
Overall Study Lost to Follow-up	11	7
Overall Study Protocol Violation	1	2
Overall Study Withdrawal by Subject	2	1

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Measure	Artemether-lumefantrine for 3 Days Plus Primaquine at Hour 24 n=154 Participants ACT: Artemether-lumefantrine (20/120 mg) as a fixed dose combination twice daily for 3 days according to weight plus low dose primaquine at hour 24	Artemether-lumefantrine for 3 Days Plus Amodiaquine for 3 Days Plus Primaquine at Hour 24 n=156 Participants TACT: Artemether-lumefantrine (20/120 mg) as a fixed dose combination twice daily for 3 days according to weight plus Amodiaquine (150mg) twice daily for 3 days according to weight plus low dose primaquine at hour 24	Total n=310 Participants Total of all reporting groups
Age, Continuous	24 years n=154 Participants	25 years n=156 Participants	25 years n=310 Participants
Sex: Female, Male Female	12 Participants n=154 Participants	24 Participants n=156 Participants	36 Participants n=310 Participants
Sex: Female, Male Male	142 Participants n=154 Participants	132 Participants n=156 Participants	274 Participants n=310 Participants
Race and Ethnicity Not Collected	—	—	0 Participants Race and Ethnicity were not collected from any participant.
Region of Enrollment Vietnam	25 Participants n=154 Participants	26 Participants n=156 Participants	51 Participants n=310 Participants
Region of Enrollment Cambodia	129 Participants n=154 Participants	130 Participants n=156 Participants	259 Participants n=310 Participants
Tympanic temperature ≥37·5°C	81 Participants n=154 Participants	83 Participants n=156 Participants	164 Participants n=310 Participants
Weight	51 kilograms (kg) STANDARD_DEVIATION 11 • n=154 Participants	51 kilograms (kg) STANDARD_DEVIATION 12 • n=156 Participants	51 kilograms (kg) STANDARD_DEVIATION 12 • n=310 Participants
Height	158 centimeters (cm) STANDARD_DEVIATION 12 • n=154 Participants	157 centimeters (cm) STANDARD_DEVIATION 14 • n=156 Participants	158 centimeters (cm) STANDARD_DEVIATION 13 • n=310 Participants
Heart rate	89 beats per minute (bpm) n=154 Participants	90 beats per minute (bpm) n=156 Participants	90 beats per minute (bpm) n=310 Participants
Respiratory rate	25 breaths per minute (bpm) n=154 Participants	26 breaths per minute (bpm) n=156 Participants	25 breaths per minute (bpm) n=310 Participants
Systolic blood pressure	113 millimeters of mercury (mmHg) STANDARD_DEVIATION 11 • n=154 Participants	113 millimeters of mercury (mmHg) STANDARD_DEVIATION 12 • n=156 Participants	113 millimeters of mercury (mmHg) STANDARD_DEVIATION 11 • n=310 Participants
Diastolic blood pressure	69 millimeters of mercury (mmHg) STANDARD_DEVIATION 8 • n=154 Participants	68 millimeters of mercury (mmHg) STANDARD_DEVIATION 8 • n=156 Participants	69 millimeters of mercury (mmHg) STANDARD_DEVIATION 8 • n=310 Participants
Heart rate-corrected QT interval (QTcB)	413 millisecond (ms) STANDARD_DEVIATION 18 • n=154 Participants	415 millisecond (ms) STANDARD_DEVIATION 17 • n=156 Participants	414 millisecond (ms) STANDARD_DEVIATION 17 • n=310 Participants
Hemoglobin (Hb)	12.8 grams per decilitre (g/dL) STANDARD_DEVIATION 1.7 • n=154 Participants	12.7 grams per decilitre (g/dL) STANDARD_DEVIATION 1.8 • n=156 Participants	12.7 grams per decilitre (g/dL) STANDARD_DEVIATION 1.7 • n=310 Participants
Pfkelch13 mutant	81 Participants n=154 Participants	93 Participants n=156 Participants	174 Participants n=310 Participants
Pfkelch13 wild-type	69 Participants n=154 Participants	62 Participants n=156 Participants	131 Participants n=310 Participants
P. falciparum, not genotyped	4 Participants n=154 Participants	1 Participants n=156 Participants	5 Participants n=310 Participants
Co-infection with P. vivax	22 Participants n=154 Participants	29 Participants n=156 Participants	51 Participants n=310 Participants
Parasitaemia	7670 Parasitaemias per µL n=154 Participants	11647 Parasitaemias per µL n=156 Participants	9464 Parasitaemias per µL n=310 Participants
Gametocytaemia	14 Participants n=154 Participants	16 Participants n=156 Participants	30 Participants n=310 Participants

PRIMARY outcome

Timeframe: 42 days

Efficacy is defined as participants, following initial parasite and fever clearance, not having a recrudescence of the original plasmodium infection and fever, up to 42 days of follow up.

Outcome measures

Measure	Artemether-lumefantrine for 3 Days Plus Primaquine at Hour 24 n=154 Participants ACT: Artemether-lumefantrine (20/120 mg) as a fixed dose combination twice daily for 3 days according to weight plus low dose primaquine at hour 24	Artemether-lumefantrine for 3 Days Plus Amodiaquine for 3 Days Plus Primaquine at Hour 24 n=156 Participants TACT: Artemether-lumefantrine (20/120 mg) as a fixed dose combination twice daily for 3 days according to weight plus Amodiaquine (150mg) twice daily for 3 days according to weight plus low dose primaquine at hour 24
Polymerase Chain Reaction Corrected Efficacy Defined as Adequate Clinical and Parasitological Response (ACPR) by Study Arm	146 Participants	151 Participants

SECONDARY outcome

Timeframe: 42 day

Population: The numbers analysed differ from the overall total as for this secondary analysis we report efficacy stratified by each of the 3 study sites.

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

Outcome measures

Measure	Artemether-lumefantrine for 3 Days Plus Primaquine at Hour 24 n=154 Participants ACT: Artemether-lumefantrine (20/120 mg) as a fixed dose combination twice daily for 3 days according to weight plus low dose primaquine at hour 24	Artemether-lumefantrine for 3 Days Plus Amodiaquine for 3 Days Plus Primaquine at Hour 24 n=156 Participants TACT: Artemether-lumefantrine (20/120 mg) as a fixed dose combination twice daily for 3 days according to weight plus Amodiaquine (150mg) twice daily for 3 days according to weight plus low dose primaquine at hour 24
42-day Polymerase Chain Reaction Corrected Efficacy According to Site/Geographic Region West Cambodia	32 Participants	35 Participants
42-day Polymerase Chain Reaction Corrected Efficacy According to Site/Geographic Region East Cambodia	91 Participants	90 Participants
42-day Polymerase Chain Reaction Corrected Efficacy According to Site/Geographic Region Vietnam	23 Participants	26 Participants

SECONDARY outcome

Timeframe: 42 day

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

Outcome measures

Measure	Artemether-lumefantrine for 3 Days Plus Primaquine at Hour 24 n=154 Participants ACT: Artemether-lumefantrine (20/120 mg) as a fixed dose combination twice daily for 3 days according to weight plus low dose primaquine at hour 24	Artemether-lumefantrine for 3 Days Plus Amodiaquine for 3 Days Plus Primaquine at Hour 24 n=156 Participants TACT: Artemether-lumefantrine (20/120 mg) as a fixed dose combination twice daily for 3 days according to weight plus Amodiaquine (150mg) twice daily for 3 days according to weight plus low dose primaquine at hour 24
Parasite Clearance Half-life	5 Hours Standard Deviation 2.5	5.5 Hours Standard Deviation 2.6

SECONDARY outcome

Timeframe: 42 day

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

Outcome measures

Measure	Artemether-lumefantrine for 3 Days Plus Primaquine at Hour 24 n=154 Participants ACT: Artemether-lumefantrine (20/120 mg) as a fixed dose combination twice daily for 3 days according to weight plus low dose primaquine at hour 24	Artemether-lumefantrine for 3 Days Plus Amodiaquine for 3 Days Plus Primaquine at Hour 24 n=156 Participants TACT: Artemether-lumefantrine (20/120 mg) as a fixed dose combination twice daily for 3 days according to weight plus Amodiaquine (150mg) twice daily for 3 days according to weight plus low dose primaquine at hour 24
Fever Clearance Time	18.3 Hours to fever clearance Standard Deviation 12.6	14.9 Hours to fever clearance Standard Deviation 9.9

SECONDARY outcome

Timeframe: 42 days

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.

Outcome measures

Measure	Artemether-lumefantrine for 3 Days Plus Primaquine at Hour 24 n=154 Participants ACT: Artemether-lumefantrine (20/120 mg) as a fixed dose combination twice daily for 3 days according to weight plus low dose primaquine at hour 24	Artemether-lumefantrine for 3 Days Plus Amodiaquine for 3 Days Plus Primaquine at Hour 24 n=156 Participants TACT: Artemether-lumefantrine (20/120 mg) as a fixed dose combination twice daily for 3 days according to weight plus Amodiaquine (150mg) twice daily for 3 days according to weight plus low dose primaquine at hour 24
Number of Severe Adverse Events by Study Arm	2 Participants	5 Participants

SECONDARY outcome

Timeframe: 42 day

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

Outcome measures

Measure	Artemether-lumefantrine for 3 Days Plus Primaquine at Hour 24 n=154 Participants ACT: Artemether-lumefantrine (20/120 mg) as a fixed dose combination twice daily for 3 days according to weight plus low dose primaquine at hour 24	Artemether-lumefantrine for 3 Days Plus Amodiaquine for 3 Days Plus Primaquine at Hour 24 n=156 Participants TACT: Artemether-lumefantrine (20/120 mg) as a fixed dose combination twice daily for 3 days according to weight plus Amodiaquine (150mg) twice daily for 3 days according to weight plus low dose primaquine at hour 24
Incidence of Adverse Events Concerning Markers of Hepatic or Renal Toxicity	53 Events	63 Events

SECONDARY outcome

Timeframe: 28 day

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

Outcome measures

Measure	Artemether-lumefantrine for 3 Days Plus Primaquine at Hour 24 n=154 Participants ACT: Artemether-lumefantrine (20/120 mg) as a fixed dose combination twice daily for 3 days according to weight plus low dose primaquine at hour 24	Artemether-lumefantrine for 3 Days Plus Amodiaquine for 3 Days Plus Primaquine at Hour 24 n=156 Participants TACT: Artemether-lumefantrine (20/120 mg) as a fixed dose combination twice daily for 3 days according to weight plus Amodiaquine (150mg) twice daily for 3 days according to weight plus low dose primaquine at hour 24
Incidence of Prolongation of the Corrected QT Interval	0 Events	0 Events

SECONDARY outcome

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

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.

Outcome measures

Measure	Artemether-lumefantrine for 3 Days Plus Primaquine at Hour 24 n=154 Participants ACT: Artemether-lumefantrine (20/120 mg) as a fixed dose combination twice daily for 3 days according to weight plus low dose primaquine at hour 24	Artemether-lumefantrine for 3 Days Plus Amodiaquine for 3 Days Plus Primaquine at Hour 24 n=156 Participants TACT: Artemether-lumefantrine (20/120 mg) as a fixed dose combination twice daily for 3 days according to weight plus Amodiaquine (150mg) twice daily for 3 days according to weight plus low dose primaquine at hour 24
Prolongation of the Corrected QT Interval	0 Events	0 Events

SECONDARY outcome

Timeframe: 24 and 48 hours

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 42 days

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 42 days

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 42 days

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Day 1 to 7, 14, 21, 28, 35, 42

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 42 day

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 42 day

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 42 day

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 48 hours

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 42 day

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 42 day

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: baseline and t = 6 hours

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 14 days

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At admission and up to day 14

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 14 days

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

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

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 42 days

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 42 days

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 7 days

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 42 days

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.

Outcome measures

Outcome data not reported

Adverse Events

Artemether-lumefantrine for 3 Days Plus Primaquine at Hour 24

Serious events: 2 serious events

Other events: 122 other events

Deaths: 0 deaths

Artemether-lumefantrine for 3 Days Plus Amodiaquine for 3 Days Plus Primaquine at Hour 24

Serious events: 5 serious events

Other events: 141 other events

Deaths: 0 deaths

Serious adverse events

Measure	Artemether-lumefantrine for 3 Days Plus Primaquine at Hour 24 n=154 participants at risk ACT: Artemether-lumefantrine (20/120 mg) as a fixed dose combination twice daily for 3 days according to weight plus low dose primaquine at hour 24	Artemether-lumefantrine for 3 Days Plus Amodiaquine for 3 Days Plus Primaquine at Hour 24 n=156 participants at risk TACT: Artemether-lumefantrine (20/120 mg) as a fixed dose combination twice daily for 3 days according to weight plus Amodiaquine (150mg) twice daily for 3 days according to weight plus low dose primaquine at hour 24
Gastrointestinal disorders gastritis	0.00% 0/154 • 42 days	0.64% 1/156 • 42 days
Gastrointestinal disorders vomiting	0.00% 0/154 • 42 days	0.64% 1/156 • 42 days
Infections and infestations severe malaria	0.00% 0/154 • 42 days	1.3% 2/156 • 42 days
Infections and infestations dengue	0.65% 1/154 • 42 days	0.00% 0/156 • 42 days
Hepatobiliary disorders Transaminitis	0.00% 0/154 • 42 days	0.64% 1/156 • 42 days
Blood and lymphatic system disorders anaemia	0.65% 1/154 • 42 days	0.00% 0/156 • 42 days

Other adverse events

Measure	Artemether-lumefantrine for 3 Days Plus Primaquine at Hour 24 n=154 participants at risk ACT: Artemether-lumefantrine (20/120 mg) as a fixed dose combination twice daily for 3 days according to weight plus low dose primaquine at hour 24	Artemether-lumefantrine for 3 Days Plus Amodiaquine for 3 Days Plus Primaquine at Hour 24 n=156 participants at risk TACT: Artemether-lumefantrine (20/120 mg) as a fixed dose combination twice daily for 3 days according to weight plus Amodiaquine (150mg) twice daily for 3 days according to weight plus low dose primaquine at hour 24
Gastrointestinal disorders vomiting	1.9% 3/154 • 42 days	7.7% 12/156 • 42 days
Gastrointestinal disorders nausea	1.9% 3/154 • 42 days	7.1% 11/156 • 42 days
General disorders dizziness	5.8% 9/154 • 42 days	10.3% 16/156 • 42 days
Gastrointestinal disorders abdominal pain	12.3% 19/154 • 42 days	14.1% 22/156 • 42 days
Gastrointestinal disorders diarrhoea	8.4% 13/154 • 42 days	10.9% 17/156 • 42 days
General disorders headache	12.3% 19/154 • 42 days	12.8% 20/156 • 42 days
General disorders fatigue	7.1% 11/154 • 42 days	9.6% 15/156 • 42 days
General disorders loss of appetite	5.8% 9/154 • 42 days	5.8% 9/156 • 42 days
Skin and subcutaneous tissue disorders itching	1.3% 2/154 • 42 days	3.2% 5/156 • 42 days
Eye disorders blurred vision	4.5% 7/154 • 42 days	2.6% 4/156 • 42 days
General disorders sleep disturbance	5.2% 8/154 • 42 days	7.7% 12/156 • 42 days
Psychiatric disorders suicidal ideation	0.00% 0/154 • 42 days	0.00% 0/156 • 42 days
Psychiatric disorders pyschiatric problems	0.00% 0/154 • 42 days	0.00% 0/156 • 42 days
Renal and urinary disorders creatinine	2.6% 4/154 • 42 days	6.4% 10/156 • 42 days
Hepatobiliary disorders total bilirubin	1.3% 2/154 • 42 days	0.00% 0/156 • 42 days
Hepatobiliary disorders alkaline phosphatase (ALP)	9.1% 14/154 • 42 days	5.1% 8/156 • 42 days
Hepatobiliary disorders alanyl transferase (ALT)	10.4% 16/154 • 42 days	13.5% 21/156 • 42 days
Hepatobiliary disorders aspartate transferase (AST)	11.0% 17/154 • 42 days	15.4% 24/156 • 42 days
Blood and lymphatic system disorders anaemia	17.5% 27/154 • 42 days	29.5% 46/156 • 42 days
Blood and lymphatic system disorders leukocytopenia	1.3% 2/154 • 42 days	0.00% 0/156 • 42 days
Blood and lymphatic system disorders neutropenia	0.65% 1/154 • 42 days	0.00% 0/156 • 42 days
Blood and lymphatic system disorders thrombocytopenia	24.7% 38/154 • 42 days	21.2% 33/156 • 42 days

Additional Information

Thomas Peto

Mahidol Oxford Tropical Medicine Research Unit (MORU)

Phone: (+66) 802 187 460

Email: tom@tropmedres.ac

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place