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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
"The study of artemether-lumefantrine or artemether-lumefantrine combined with amodiaquine will be a two-arm randomized open label comparative study.
The main activity proposed is a series of detailed in vivo clinical, parasitological and pharmacological assessments in 600 subjects across 2 sites in Cambodian (400 subjects) and 2 sites in Vietnam (200 subjects). The subjects will be randomized between the ACT artemether-lumefantrine and the TACT artemether-lumefantrine+amodiaquine.
Parasite clearance rates will be assessed by repeated assessments of the parasite counts after the start of the antimalarial treatments. Efficacy, safety and tolerability of ACTs and TACTs will be assessed through weekly follow up visits where vital signs, symptom questionnaires, physical examinations, blood smears, biochemistry assays and full blood counts will be performed.
Ex vivo assessments of parasite susceptibility to artemisinins and partner drugs will be measured and compared to historical data, clinical phenotype and other sites in an effort to identify artemisinin and partner drug resistance.
This study will obtain data on the effect of antimalarials on the corrected QT intervals. In addition, the effects of antimalarials on factors such as post-treatment haematocrit and haemoglobin levels will be assessed. Extensive pharmacokinetic analysis will allow for an assessment of drug-drug interactions.
Plasma histidine-rich protein 2 (HRP2) levels (a marker of parasite biomass) that could potentially serve for the estimation of parasitaemia dynamics before and after treatment will be measured and subsequently modelled."
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| ACT | Active Comparator | Artemether-lumefantrine for 3 days plus primaquine at hour 24 |
|
| TACT | Experimental | Artemether-lumefantrine for 3 days plus Amodiaquine for 3 days plus primaquine at hour 24 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ACT | Drug | 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 |
|
| Measure | Description | Time Frame |
|---|---|---|
| Polymerase Chain Reaction Corrected Efficacy Defined as Adequate Clinical and Parasitological Response (ACPR) by Study Arm | 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. | 42 days |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 42 day |
| Parasite Clearance Half-life |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Siem Pang Health Center | Siem Pang | Stung Treng | 1803 | Cambodia | ||
| Pailin Referral Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35276064 | Background | Peto TJ, Tripura R, Callery JJ, Lek D, Nghia HDT, Nguon C, Thuong NTH, van der Pluijm RW, Dung NTP, Sokha M, Van Luong V, Long LT, Sovann Y, Duanguppama J, Waithira N, Hoglund RM, Chotsiri P, Chau NH, Ruecker A, Amaratunga C, Dhorda M, Miotto O, Maude RJ, Rekol H, Chotivanich K, Tarning J, von Seidlein L, Imwong M, Mukaka M, Day NPJ, Hien TT, White NJ, Dondorp AM. Triple therapy with artemether-lumefantrine plus amodiaquine versus artemether-lumefantrine alone for artemisinin-resistant, uncomplicated falciparum malaria: an open-label, randomised, multicentre trial. Lancet Infect Dis. 2022 Jun;22(6):867-878. doi: 10.1016/S1473-3099(21)00692-7. Epub 2022 Mar 8. |
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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.
Enrolled at hospitals and health centres 18 March 2018 to 30 January 2020
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| ID | Title | Description |
|---|---|---|
| FG000 | 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 |
| FG001 | 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 |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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 |
| BG001 | Artemether-lumefantrine for 3 Days Plus Amodiaquine for 3 Days Plus Primaquine at Hour 24 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Polymerase Chain Reaction Corrected Efficacy Defined as Adequate Clinical and Parasitological Response (ACPR) by Study Arm | 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. | Posted | Count of Participants | Participants | 42 days |
|
42 days
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| gastritis | Gastrointestinal disorders | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| vomiting | Gastrointestinal disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Thomas Peto | Mahidol Oxford Tropical Medicine Research Unit (MORU) | (+66) 802 187 460 | tom@tropmedres.ac |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Nov 22, 2017 | Oct 12, 2021 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jun 28, 2020 | Oct 12, 2021 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D016778 | Malaria, Falciparum |
| D008288 | Malaria |
| D011528 | Protozoan Infections |
| D066126 | Cardiotoxicity |
| ID | Term |
|---|---|
| D010272 | Parasitic Diseases |
| D007239 | Infections |
| D000096724 | Mosquito-Borne Diseases |
| D000079426 | Vector Borne Diseases |
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| ID | Term |
|---|---|
| C038435 | bis(tetraheptylammonium)tetraiodocyclopentane tellurate(IV) |
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open-label randomised trial
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| TACT | Drug | 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 assessed by microscopy as primary parameter to determine parasite clearance |
| 42 day |
| Fever Clearance Time | The time taken for the tympanic temperature to fall below 37.5ËšC and remain there for at least 24 hours | 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. | 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 | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | 42 days |
| Pailin |
| 2401 |
| Cambodia |
| Hospital for Tropical Diseases of Khanh Hoa, | Vạn Giã | Khanh Hoa | Vietnam |
| Phuoc Long Hospital | PhÆ°á»›c Long | Phuoc | Vietnam |
| Protocol Violation |
|
| Withdrawal by Subject |
|
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 |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| Tympanic temperature ≥37·5°C | Count of Participants | Participants |
|
| Weight | Mean | Standard Deviation | kilograms (kg) |
|
| Height | Mean | Standard Deviation | centimeters (cm) |
|
| Heart rate | Median | Inter-Quartile Range | beats per minute (bpm) |
|
| Respiratory rate | Median | Inter-Quartile Range | breaths per minute (bpm) |
|
| Systolic blood pressure | Mean | Standard Deviation | millimeters of mercury (mmHg) |
|
| Diastolic blood pressure | Mean | Standard Deviation | millimeters of mercury (mmHg) |
|
| Heart rate-corrected QT interval (QTcB) | Mean | Standard Deviation | millisecond (ms) |
|
| Hemoglobin (Hb) | Mean | Standard Deviation | grams per decilitre (g/dL) |
|
| Pfkelch13 mutant | Count of Participants | Participants |
|
| Pfkelch13 wild-type | Count of Participants | Participants |
|
| P. falciparum, not genotyped | Count of Participants | Participants |
|
| Co-infection with P. vivax | Count of Participants | Participants |
|
| Parasitaemia | Geometric Mean | Inter-Quartile Range | Parasitaemias per µL |
|
| Gametocytaemia | Count of Participants | 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
|
|
|
| Secondary | 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. | The numbers analysed differ from the overall total as for this secondary analysis we report efficacy stratified by each of the 3 study sites. | Posted | Count of Participants | Participants | 42 day |
|
|
|
| Secondary | Parasite Clearance Half-life | Parasite clearance half-life assessed by microscopy as primary parameter to determine parasite clearance | Posted | Mean | Standard Deviation | Hours | 42 day |
|
|
|
| Secondary | Fever Clearance Time | The time taken for the tympanic temperature to fall below 37.5ËšC and remain there for at least 24 hours | Posted | Mean | Standard Deviation | Hours to fever clearance | 42 day |
|
|
|
| Secondary | 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. | Posted | Number | Participants | 42 days |
|
|
|
| Secondary | Incidence of Adverse Events Concerning Markers of Hepatic or Renal Toxicity | Total bilirubin, Alanine transaminase, Aspartate transaminase, Alkaline phosphatase and creatinine will be measured | Posted | Number | Events | 42 day |
|
|
|
| Secondary | 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. | Posted | Number | Events | 28 day |
|
|
|
| Secondary | 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. | Posted | Number | Events | Hour 4, Hour 24, Hour 28, Hour 48, Hour 52, Hour 60, Hour 64, Day 7 and Day 28 and between these time points |
|
|
|
| Secondary | 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. | Not Posted | Dec 2022 | 24 and 48 hours | Participants |
| Secondary | 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. | Not Posted | Dec 2022 | 42 days | Participants |
| Secondary | 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. | Not Posted | Dec 2022 | 42 days | Participants |
| Secondary | 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. | Not Posted | Dec 2022 | 42 days | Participants |
| Secondary | 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. | Not Posted | Dec 2022 | Day 1 to 7, 14, 21, 28, 35, 42 | Participants |
| Secondary | 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. | Not Posted | Dec 2022 | 42 day | Participants |
| Secondary | 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. | Not Posted | Dec 2022 | 42 day | Participants |
| Secondary | 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. | Not Posted | Dec 2022 | 42 day | Participants |
| 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 | 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. | Not Posted | Dec 2022 | 48 hours | Participants |
| Secondary | 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. | Not Posted | Dec 2022 | 42 day | Participants |
| Secondary | 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. | Not Posted | Dec 2022 | 42 day | Participants |
| Secondary | 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. | Not Posted | Dec 2022 | baseline and t = 6 hours | Participants |
| Secondary | 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. | Not Posted | Dec 2022 | 14 days | Participants |
| Secondary | 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. | Not Posted | Dec 2022 | At admission and up to day 14 | Participants |
| Secondary | 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. | Not Posted | Dec 2022 | 14 days | Participants |
| Secondary | 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. | Not Posted | Dec 2022 | At admission & subjects with recurrent parasitaemia, up to 42 days | Participants |
| Secondary | 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. | Not Posted | Dec 2022 | 42 days | Participants |
| Secondary | 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. | Not Posted | Dec 2022 | 42 days | Participants |
| Secondary | 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. | Not Posted | Dec 2022 | 7 days | Participants |
| Secondary | 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. | Not Posted | Dec 2022 | 42 days | Participants |
| 0 |
| 154 |
| 2 |
| 154 |
| 122 |
| 154 |
| EG001 | 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 | 0 | 156 | 5 | 156 | 141 | 156 |
| vomiting | Gastrointestinal disorders | Systematic Assessment |
|
| severe malaria | Infections and infestations | Systematic Assessment |
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| dengue | Infections and infestations | Systematic Assessment |
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| Transaminitis | Hepatobiliary disorders | Systematic Assessment |
|
| anaemia | Blood and lymphatic system disorders | Systematic Assessment |
|
| nausea | Gastrointestinal disorders | Systematic Assessment |
|
| dizziness | General disorders | Systematic Assessment |
|
| abdominal pain | Gastrointestinal disorders | Systematic Assessment |
|
| diarrhoea | Gastrointestinal disorders | Systematic Assessment |
|
| headache | General disorders | Systematic Assessment |
|
| fatigue | General disorders | Systematic Assessment |
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| loss of appetite | General disorders | Systematic Assessment |
|
| itching | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| blurred vision | Eye disorders | Systematic Assessment |
|
| sleep disturbance | General disorders | Systematic Assessment |
|
| suicidal ideation | Psychiatric disorders | Systematic Assessment |
|
| pyschiatric problems | Psychiatric disorders | Systematic Assessment |
|
| creatinine | Renal and urinary disorders | Systematic Assessment |
|
| total bilirubin | Hepatobiliary disorders | Systematic Assessment |
|
| alkaline phosphatase (ALP) | Hepatobiliary disorders | Systematic Assessment |
|
| alanyl transferase (ALT) | Hepatobiliary disorders | Systematic Assessment |
|
| aspartate transferase (AST) | Hepatobiliary disorders | Systematic Assessment |
|
| anaemia | Blood and lymphatic system disorders | Systematic Assessment |
|
| leukocytopenia | Blood and lymphatic system disorders | Systematic Assessment |
|
| neutropenia | Blood and lymphatic system disorders | Systematic Assessment |
|
| thrombocytopenia | Blood and lymphatic system disorders | Systematic Assessment |
|
Not provided
Not provided
Not provided
| D006331 |
| Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D064420 | Drug-Related Side Effects and Adverse Reactions |
| D064419 | Chemically-Induced Disorders |
| D011832 | Radiation Injuries |
| D014947 | Wounds and Injuries |
| East Cambodia |
|
|
| Vietnam |
|
|