Plasmodium FalciparumPhase 3TACTKenyaNCT03452475
Comparison of Arterolane-piperaquine Versus Arterolane-piperaquine+Mefloquine Versus Artemether-lumefantrine in Kenyan Children
A Phase 3 study testing Arterolane-piperaquine, Arterolane-piperaquine+mefloquine and Artemether-lumefantrine in people with Plasmodium Falciparum, run by University of Oxford at 1 site in Kenya.
Trial summary
This open-label randomised controlled clinical trial will compare the safety, tolerability, therapeutic efficacy and pharmacokinetics and pharmacodynamics of arterolane-piperaquine, arterolane-piperaquine plus mefloquine versus artemether-lumefantrine.in children with uncomplicated falciparum malaria in Kilifi, Kenya. Read more about this study
- Who is it for?
- Ages 2 to 12 years
- Conditions the study is for
- Plasmodium Falciparum
- What is being tested?
- Arterolane-piperaquine, Arterolane-piperaquine+mefloquine and Artemether-lumefantrine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 219 participants
- Where
- 1 siteKenya
- Study dates
- 7 Mar 2018to 3 Jun 2019
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 12 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Male or female aged 2 years to <13-year-old
- Uncomplicated falciparum malaria as defined as:
- Positive blood smear with asexual forms of P. falciparum (may be mixed with non-falciparum species)
- Parasitaemia between 5,000-250,000 parasites/µL
- Fever defined as tympanic temperature >37.5°C or history of fever within last 48 hours
- Ability to take oral medication
- Willingness and ability to comply with study protocol for study duration
- Written informed consent given to participate in the trial
Who cannot join
- Signs of severe/complicated malaria*
- Any clinical reason suggesting that the child's treatment should be given immediately and not delayed during the transfer to Kilifi County Hospital in the opinion of the treating physician.
- Acute illness other than malaria requiring urgent systemic treatment as assessed by the treating physician
- Previous splenectomy
- Treatment with artemisinin or ACT within the previous 7 days
- Treatment with mefloquine in the 2 months prior to presentation
Show all 10Show fewer
- Known hypersensitivity or contraindication to arterolane-piperaquine, DHA-piperaquine, artemisinin, mefloquine (epilepsy, major psychiatric illness) or primaquine
- QTc interval >450 milliseconds at point of presentation
- Known personal or family history of cardiac conduction problems
- Participation within another clinical trial in the previous 3 months
Trial locations and contacts
1 site in 1 country.
About this study
Official title: An Open-label Randomised Trial to Assess the Therapeutic Efficacy and Tolerability of Arterolane-piperaquine Plus Single Low Dose Primaquine Versus Arterolane-piperaquine Plus Mefloquine and Single Low Dose Primaquine Versus Artemether-lumefantrine Plus Single Low Dose Primaquine in the Treatment of Uncomplicated Falciparum Malaria in Children in Kenya
This open-label randomised controlled clinical trial will compare the safety, tolerability, therapeutic efficacy and pharmacokinetics and pharmacodynamics of arterolane-piperaquine, arterolane-piperaquine plus mefloquine versus artemether-lumefantrine.in children with uncomplicated falciparum malaria in Kilifi, Kenya. This study will also provide an up to date insight on the current presence of antimalarial resistance in this site.
In addition, all children will be treated with a single low dose of primaquine, dosing is age based.
The investigators will recruit 219 patients aged 2 years to 12 years with acute uncomplicated falciparum malaria in Kilifi County Hospital.
- Conditions
- Plasmodium Falciparum
- Being tested
- Arterolane-piperaquine, Arterolane-piperaquine+mefloquine, Artemether-lumefantrine
- Medical subject headings
- Malaria, Falciparum
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Arterolane-piperaquineDrug
Arterolane maleate-piperaquine phosphate tablets (37.5 mg/187.5 mg)
Arterolane-piperaquine+mefloquineDrug
Arterolane maleate-piperaquine phosphate tablets (37.5 mg/187.5 mg) Mefloquine tablets (250 mg)
Artemether-lumefantrineDrug
Artemether-lumefantrine tablets (20 mg/120 mg)
| Study group | Role | What they receive |
|---|---|---|
| Arterolane-piperaquine | Active comparator | Arterolane-piperaquine for 3 days Receives: Drug: Arterolane-piperaquine |
| Arterolane-piperaquine+mefloquine | Active comparator | Arterolane-piperaquine + mefloquine for 3 days Receives: Drug: Arterolane-piperaquine+mefloquine |
| Artemether-lumefantrine | Active comparator | Artemether-lumefantrine for 3 days Receives: Drug: Artemether-lumefantrine |
What is being measured
The primary outcome is the main question the study is designed to answer.
42-day PCR corrected adequate clinical and parasitological response (ACPR) by day 42 by study arm
Measured: 42 days
Secondary outcomes (21)
Parasite clearance half-life
Parasite clearance half-life is assessed by entering the parasite counts (assessed by microscopy) in the WWARN PCE calculator
Measured: 42 days
Parasite reduction rates
Parasite reduction rates and ratios at 24 and 48 hours assessed by microscopy
Measured: 24 and 48 hours
Parasite count to fall 50%
Time for parasite count to fall 50% of initial parasite density
Measured: 42 days
Parasite count to fall 90%
Time for parasite count to fall 90% of initial parasite density
Measured: 42 days
Fever clearance time
The time taken for the tympanic temperature to fall below 37.5˚C and remain there for at least 24 hours
Measured: 42 days
Incidence of clinical adverse events and serious adverse events
Measured: 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
Measured: 42 days
Incidence of prolongation of the corrected QT interval
Incidence of the prolongation of the corrected QT interval above 500 ms or > 60 ms above baseline values
Measured: 42 days
Prolongation of the corrected QT interval
Prolongation of the corrected QT interval compared at hour 4, hour 24, hour 28, hour 48 and hour 52 compared to baseline
Measured: Baseline, hour 4, hour 24, hour 28, hour 48 and hour 52
Change in haematocrit
Change in haematocrit at hour 24, hour 48, hour 72, day 7, day 14, day 21, day 28, day 35 and day 42 according to geographical location and study arm, stratified for G6PD status
Measured: Baseline, hour 24, hour 48, hour 72, day 7, day 14, day 21, day 28, day 35 and day 42
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
Measured: 42 days
Prevalence of Kelch13 mutations of known significance
Prevalence of Kelch13 mutations of known significance
Measured: Baseline
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
Measured: Baseline
Genome wide association with in vivo/in vitro sensitivity parasite phenotype
Genome wide association with in vivo/in vitro sensitivity parasite phenotype
Measured: Baseline
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
Measured: Baseline and 6 hours
Proportion of patients with gametocytaemia before, during and after treatment
Proportion of patients with gametocytaemia before, during and after treatment
Measured: 42 days
Levels of RNA transcription coding for male or female gametocytes
Levels of RNA transcription coding for male or female gametocytes at admission
Measured: Baseline
In vitro sensitivity of P. falciparum to artemisinins and partner drugs
Measured: Baseline and day recurrent infection
Pharmacokinetic profiles and interactions (Cmax) of arterolane and partner drugs
Pharmacokinetic profiles and interactions (Cmax) of arterolane and partner drugs
Measured: 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
Measured: 7 days
Data on recent travel and current location of living
Measured: Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Mar 2018
- Study start7 Mar 2018
- Primary completion3 Jun 2019
- Study completion3 Jun 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Plasmodium FalciparumStudies of the same condition, open and under way.
- More trials run by University of OxfordThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- randomised 1:1:1 to one of the three treatment arms
- Masking
- None (open label)
- Enrolment
- 219 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Collaborators
- Mahidol Oxford Tropical Medicine Research Unit
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03452475
- Sponsor's protocol ID
- MAL17009
- Acronym
- TACTKenya
- Status last verified
- Sep 2021
- First submitted
- 1 Feb 2018
- Last updated
- 29 Sep 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Anonymized data will be entered to a database maintained by Mahidol-Oxford-Research-Unit. Individual-level anonymized data will be shared with medical regulators where appropriate. For wider stake-holder engagement and the medical community summary-level statistical analyses will be shared. Information collected or generated during this study may be anonymised for use to support new research and policies for antimalarial drug resistance. Any future research using information from this study must first be approved by a local or national expert committee to make sure that the interests of participants and their communities are protected.
Publications
Hamaluba M, van der Pluijm RW, Weya J, Njuguna P, Ngama M, Kalume P, Mwambingu G, Ngetsa C, Wambua J, Boga M, Mturi N, Lal AA, Khuroo A, Taylor WRJ, Goncalves S, Miotto O, Dhorda M, Mutinda B, Mukaka M, Waithira N, Hoglund RM, Imwong M, Tarning J, Day NPJ, White NJ, Bejon P, Dondorp AM. Arterolane-piperaquine-mefloquine versus arterolane-piperaquine and artemether-lumefantrine in the treatment of uncomplicated Plasmodium falciparum malaria in Kenyan children: a single-centre, open-label, randomised, non-inferiority trial. Lancet Infect Dis. 2021 Oct;21(10):1395-1406. doi: 10.1016/S1473-3099(20)30929-4. Epub 2021 Jun 7.
PubMed 34111412
Study at a glance
From the registry record, last updated by the sponsor on 29 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label Randomised Trial to Assess the Therapeutic Efficacy and Tolerability of Arterolane-piperaquine Plus Single Low Dose Primaquine Versus Arterolane-piperaquine Plus Mefloquine and Single Low Dose Primaquine Versus Artemether-lumefantrine Plus Single Low Dose Primaquine in the Treatment of Uncomplicated Falciparum Malaria in Children in Kenya
- ClinicalTrials.gov ID
- NCT03452475
- Acronym / sponsor ID
- TACTKenya / MAL17009
- Conditions
- Plasmodium Falciparum
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 219 participants (actual)
- Lead sponsor
- University of OxfordUniversity, hospital or other
- Collaborators
- Mahidol Oxford Tropical Medicine Research Unit
- Study start
- 7 Mar 2018 (actual)
- Primary completion
- 3 Jun 2019 (actual)
- Study completion
- 3 Jun 2019 (actual)
- First posted
- 2 Mar 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This open-label randomised controlled clinical trial will compare the safety, tolerability, therapeutic efficacy and pharmacokinetics and pharmacodynamics of arterolane-piperaquine, arterolane-piperaquine plus mefloquine versus artemether-lumefantrine.in children with uncomplicated falciparum malaria in Kilifi, Kenya. This study will also provide an up to date insight on the current presence of antimalarial resistance in this site.
In addition, all children will be treated with a single low dose of primaquine, dosing is age based.
The investigators will recruit 219 patients aged 2 years to 12 years with acute uncomplicated falciparum malaria in Kilifi County Hospital.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- randomised 1:1:1 to one of the three treatment arms
| Arm | Type | Receives |
|---|---|---|
| Arterolane-piperaquine | Active comparator | Drug: Arterolane-piperaquineArterolane-piperaquine for 3 days |
| Arterolane-piperaquine+mefloquine | Active comparator | Drug: Arterolane-piperaquine+mefloquineArterolane-piperaquine + mefloquine for 3 days |
| Artemether-lumefantrine | Active comparator | Drug: Artemether-lumefantrineArtemether-lumefantrine for 3 days |
Who may qualify
- Ages
- 2 to 12 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (8 listed)
- Male or female aged 2 years to <13-year-old
- Uncomplicated falciparum malaria as defined as:
- Ability to take oral medication
- Willingness and ability to comply with study protocol for study duration
- Written informed consent given to participate in the trial
Key exclusion criteria (10 listed)
- Signs of severe/complicated malaria*
- Any clinical reason suggesting that the child's treatment should be given immediately and not delayed during the transfer to Kilifi County Hospital in the opinion of the treating physician.
- Acute illness other than malaria requiring urgent systemic treatment as assessed by the treating physician
- Previous splenectomy
- Treatment with artemisinin or ACT within the previous 7 days
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Arterolane-piperaquineArterolane maleate-piperaquine phosphate tablets (37.5 mg/187.5 mg) | Drug | Arterolane-piperaquine |
| Arterolane-piperaquine+mefloquineArterolane maleate-piperaquine phosphate tablets (37.5 mg/187.5 mg) Mefloquine tablets (250 mg) | Drug | Arterolane-piperaquine+mefloquine |
| Artemether-lumefantrineArtemether-lumefantrine tablets (20 mg/120 mg) | Drug | Artemether-lumefantrine |
Primary outcome
42-day PCR corrected adequate clinical and parasitological response (ACPR) by day 42 by study arm
Time frame: 42 days
21 secondary outcomes
Parasite clearance half-life
Time frame: 42 days
Parasite reduction rates
Time frame: 24 and 48 hours
Parasite count to fall 50%
Time frame: 42 days
Parasite count to fall 90%
Time frame: 42 days
Fever clearance time
Time frame: 42 days
Incidence of clinical adverse events and serious adverse events
Time frame: 42 days
Incidence of adverse events concerning markers of hepatic or renal toxicity
Time frame: 42 days
Incidence of prolongation of the corrected QT interval
Time frame: 42 days
Prolongation of the corrected QT interval
Time frame: Baseline, hour 4, hour 24, hour 28, hour 48 and hour 52
Change in haematocrit
Time frame: Baseline, hour 24, hour 48, hour 72, day 7, day 14, day 21, day 28, day 35 and day 42
Proportion of patients that reports completing a full course of observed TACT or ACT
Time frame: 42 days
Prevalence of Kelch13 mutations of known significance
Time frame: Baseline
Prevalence/incidence of other genetic markers of antimalarial drug resistance such as multidrug resistance gene 1 copy number and multidrug resistance gene 1 mutations
Time frame: Baseline
Genome wide association with in vivo/in vitro sensitivity parasite phenotype
Time frame: Baseline
A comparison of transcriptomic patterns between sensitive and resistant parasites
Time frame: Baseline and 6 hours
Proportion of patients with gametocytaemia before, during and after treatment
Time frame: 42 days
Levels of RNA transcription coding for male or female gametocytes
Time frame: Baseline
In vitro sensitivity of P. falciparum to artemisinins and partner drugs
Time frame: Baseline and day recurrent infection
Pharmacokinetic profiles and interactions (Cmax) of arterolane and partner drugs
Time frame: 42 days
Day 7 drug levels of partner drugs in association with treatment efficacy and treatment arm
Time frame: 7 days
Data on recent travel and current location of living
Time frame: Baseline
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Sep 2021.
- Derived from this study: PubMed 34111412Hamaluba M, van der Pluijm RW, Weya J, Njuguna P, Ngama M, Kalume P, Mwambingu G, Ngetsa C, Wambua J, Boga M, Mturi N, Lal AA, Khuroo A, Taylor WRJ, Goncalves S, Miotto O, Dhorda M, Mutinda B, Mukaka M, Waithira N, Hoglund RM, Imwong M, Tarning J, Day NPJ, White NJ, Bejon P, Dondorp AM. Arterolane-piperaquine-mefloquine versus arterolane-piperaquine and artemether-lumefantrine in the treatment of uncomplicated Plasmodium falciparum malaria in Kenyan children: a single-centre, open-label, randomised, non-inferiority trial. Lancet Infect Dis. 2021 Oct;21(10):1395-1406. doi: 10.1016/S1473-3099(20)30929-4. Epub 2021 Jun 7.
- Individual participant dataSharing planned: Undecided. Anonymized data will be entered to a database maintained by Mahidol-Oxford-Research-Unit. Individual-level anonymized data will be shared with medical regulators where appropriate. For wider stake-holder engagement and the medical community summary-level statistical analyses will be shared. Information collected or generated during this study may be anonymised for use to support new research and policies for antimalarial drug resistance. Any future research using information from this study must first be approved by a local or national expert committee to make sure that the interests of participants and their communities are protected.
Related trials for Plasmodium Falciparum
Not yet recruiting
Permethrin-Treated Baby Wraps for Malaria Prevention in Refugee Settings
Malaria (Plasmodium Falciparum), Malaria Incidence
RecruitingPhase 2
Platform Study to Evaluate the Efficacy and Safety of Anti-malarial Agents in Participants With Uncomplicated Plasmodium Falciparum Malaria (Cohort C2)
Uncomplicated Plasmodium Falciparum Malaria
Active, not recruitingPhase 2
Infant Malaria Vaccine Schedule Optimization
Malaria Vaccines, Malaria (Plasmodium Falciparum)
Not yet recruitingObservational study
Ethiopian Antimalarial Therapeutic Efficacy Study 2026
Plasmodium Vivax Malaria Without Complication, Plasmodium Falciparum Malaria (Uncomplicated)
RecruitingPhase 3
Serological Testing and Treatment for Plasmodium Vivax Malaria: a Trial in Ethiopia and Madagascar
Malaria Vivax, Malaria Falciparum
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Arterolane-piperaquine, Arterolane-piperaquine+mefloquine and Artemether-lumefantrine in people with Plasmodium Falciparum, run by University of Oxford at 1 site in Kenya.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Kenya. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
42-day PCR corrected adequate clinical and parasitological response (ACPR) by day 42 by study arm (time frame: 42 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03452475, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Sep 2021; AzTrials last refreshed its copy on 8 Nov 2026.