ACT vs CQ With Tafenoquine for P. Vivax Mono-infection
Trial statusRecruiting
Trial phasePhase 4
Trial typeInterventional
Biological sexAll
Age18+
SponsorShoklo Malaria Research Unit
About this trial
In this area of Greater Mekong Subregion (GMS), vivax malaria is the most common kind of malaria. It can stay very long in the liver, and come out later to make another episode of illness. This can happen many times even without a mosquito bite. Only 8-aminoquinoline drugs can kill the liver forms of the malaria parasite. One of these drugs is called primaquine, and it has been used all over the world for a long time. There is now a new formulation of this 8-aminoquinoline drug called tafenoquine that can also treat the malaria in the liver. The main benefit of this drug is that it is a single dose, which makes much convenient for the patients as well as for the malaria control program than conventional 14 days of primaquine. Recent research suggests that ACT (Artemisinin Combination Therapy) may antagonise the efficacy of tafenoquine (Baird et al. 2020 ASTMH Annual Meeting) . This could prevent the use of tafenoquine in areas with chloroquine resistant P. vivax parasites where national malaria programmes recommend ACTs for vivax malaria. Also, currently recommended tafenoquine dose is sub-optimal: 300 mg dose proved significantly inferior to low dose primaquine in a meta-analysis of the phase 3 studies when restricted to the Southeast Asian region (Llanos-Cuentas et al. 2019 NEJM; Watson et al. 2022a Elife). A tafenoquine dose of 450mg is predicted to provide \>90% of the maximal effect. The objective of this research is to find out whether 450 mg dose of tafenoquine can be combined effectively with ACT providing a short course treatment for P. vivax malaria.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Patients with P. vivax mono-infection as diagnosed by Rapid Diagnostic Test
Fever or history of fever in the previous 7 days
Quantitative G6PD activity ≥70% of the population median i.e., ≥6.1U/gHb
Age > 18 years, Weight >35 kg
Disqualifiers
Coincident P. falciparum malaria or other infections
Pregnancy
Lactation
Hb < 8 g/dL
Trial design
Design model
Parallel
Treatments tested in this trial
Dihydroartemisinin-piperaquine plus tafenoquine (450 mg adult dose)
Drug* Dihydroartemisinin-Piperaquine will be purchased as Duo-Cotecxin® Beijing Holley-Cotec Pharmaceuticals Co., Ltd, China). One tablet contains 40 mg of dihydroartemisinin and 320 mg piperaquine (i.e. a 1:8 ratio). A weight-based regimen containing a total dose of approximately 7 mg/kg DHA and 55 mg/kg piperaquine given in 3 divided doses once daily. * Tafenoquine KODATEF® 150 mg film-coated tablets will be purchased from Biocelect (Suite 5.02, Level 5, 139 Macquarie Street, Sydney NSW, 2000 Australia), 450 mg (4 1/2 tablets) will be given.
Chloroquine plus Tafenoquine (450 mg adult dose)
Drug* Chloroquine will be dosed as a 25 mg/kg base given in divided doses of 10 mg/kg orally on days 0 and 1, and in 5 mg/kg dose on day 2. Tablets will be obtained from Government Pharmaceutical Organization (GPO) in Bangkok, Thailand and supplied as 250 mg tablets (155.3 mg base). * Tafenoquine KODATEF® 150 mg film-coated tablets will be purchased from Biocelect (Suite 5.02, Level 5, 139 Macquarie Street, Sydney NSW, 2000 Australia), 450 mg (4 1/2 tablets) will be given.
Artemether-Lumefantrine plus Tafenoquine (450 mg adult dose)
Drug* Artemether-Lumefantrine will be given at a standard dose of 20/120 mg twice daily for three days. (AL will be purchase from Novartis Pharma Services AG- Lichtstrasse 35, CH-4056 Basel, Switzerland.) * Tafenoquine KODATEF® 100 mg film-coated tablets will be purchased from Biocelect (Suite 5.02, Level 5, 139 Macquarie Street, Sydney NSW, 2000 Australia), 450 mg (4 1/2 tablets) will be given.
Treatment groups
606 Participants
are divided into 3 treatment groupsGroup A: Dihydroartemisinin-piperaquine plus tafenoquine (450 mg adult dose)Experimental treatment 1 intervention
Group B: Chloroquine plus Tafenoquine (450 mg adult dose)Experimental treatment 1 intervention
Group C: Artemether-Lumefantrine plus Tafenoquine (450 mg adult dose)Experimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Determine whether ACTs (Artemether-Lumefantrine or dihydroartemisinin-piperaquine (DHA-PPQ)) plus TQ is non-inferior to CQ plus TQ
Number of participants with relapse-free efficacy (measured by PCR) in three arms
Time frame
Month-4Secondary outcomes
1
Characterise the safety and tolerability of three regimens
Number of participants with drop in hemoglobin ≥2 g/dL and/or hematocrit by ≥10% from baseline Number of participants with Non-serious Adverse Events (Non-SAEs) and Serious Adverse Events (SAEs)
Time frame
Day3, Day7, Month1, Month2, Month3, Month42
Characterise population pharmacokinetics of tafenoquine in three treatments
Area Under the Curve From Time-0 Extrapolated to Infinite Time (AUC0-infinite time) of Tafenoquine
Time frame
Day3, Day7, Month1, Month2, Month3, Month43
Met-Haemoglobin level a vivo pharmacodynamic proxy of oxidative antimalarial activity of tafenoquine
Percentage increase in Methaemoglobin level compared across three arms
Time frame
Day3, Day7Other outcomes
1
Genotyping and probabilistic assessment to differentiate P. vivax relapse from reinfection
Number of participants with relapse and reinfection in three regimens
Time frame
Day3, Day7, Month1, Month2, Month3, Month42
Evaluate the performance of village health workers as safe prescribers of tafenoquine radical cure
Number of participants with correct dosing, adverse event recording including haemoglobin drops
Time frame
Day3, Day7, Month1, Month2, Month3, Month4Sponsors and contacts
Click on the lead sponsor to view all of their trials.
Shoklo Malaria Research Unit
Lead sponsor
University of Oxford
Sponsor institution
Mahidol Oxford Tropical Medicine Research Unit
Collaborator
University of Oxford
Collaborator
Source ClinicalTrials.gov