Plasmodium Falciparum Malaria (Uncomplicated) Clinical Trial
— DeTACT-AfricaOfficial title:
A Multi-centre Randomised Controlled Non-inferiority Trial to Compare the Efficacy, Safety and Tolerability of Triple Artemisinin-based Combination Therapies Versus First-line ACTs + Placebo for the Treatment of Uncomplicated Plasmodium Falciparum Malaria in Africa
A partially blinded randomised controlled non-inferiority trial comparing the efficacy, tolerability and safety of Triple ACTs artemether-lumefantrine+amodiaquine (AL+AQ) and artesunate-mefloquine+piperaquine (ASMQ+PPQ) and the ACTs artemether-lumefantrine+placebo (AL+PBO), artesunate-mefloquine+placebo (ASMQ+PBO) (with single-low dose primaquine in some sites) for the treatment of uncomplicated Plasmodium falciparum malaria to assess and compare their efficacy, safety, tolerability.
Status | Recruiting |
Enrollment | 3240 |
Est. completion date | September 2024 |
Est. primary completion date | March 15, 2024 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 6 Months to 12 Years |
Eligibility | Inclusion Criteria: - Male or female, aged =6 months to <12 years (For Gambia, Rwanda sites only: =6 months) - Ability to take oral medication - Acute uncomplicated P. falciparum monoinfection - Asexual P. falciparum parasitaemia: 1,000/µL to =10% parasitaemia, determined on a peripheral blood film (At Gambia, Rwanda sites only: For subjects =12 years - 1000/µL to 200,000/µL) - Fever defined as = 37.5°C tympanic temperature or a history of fever within the last 24 hours - Written informed consent by the subject or by parent/guardian in case of children lower than the age of consent and assent if required (per local regulations) - Willingness and ability of the subjects or parents/guardians to comply with the study protocol for the duration of the study Exclusion Criteria: - Signs of severe malaria (adapted from WHO criteria) - Patients not fulfilling criteria for severe malaria but with another indication for parenteral antimalarial treatment at the discretion of the treating physician - Haematocrit <15% at screening (For Gambia, Rwanda sites only: For subjects =12 years - Haematocrit <20% at screening) - Subjects who have received artemisinin or a derivative within the previous 7 days OR lumefantrine or amodiaquine within the previous 14 days OR mefloquine or piperaquine within the previous 30 days - In applicable countries: use of seasonal malaria chemoprophylaxis (SMC) within the last 14 days. - Acute illness other than malaria requiring systemic treatment - Severe acute malnutrition (in Niger only - only those patients with Severe Acute Malnutrition and complications requiring inpatient nutritional treatment will be excluded) - Known HIV infection - Known tuberculosis infection - For females: post-menarche (For Gambia, Rwanda sites only: females who are pregnant, trying to get pregnant or are lactating) - History of allergy or known contraindication to any of the study drugs, including neuropsychiatric disorders and epilepsy - Previous splenectomy - Enrolment in DeTACT in the previous 3 months - Participation in another interventional study in the previous 3 months |
Country | Name | City | State |
---|---|---|---|
Burkina Faso | Institut des Sciences et Techniques (INSTech) | Bobo-Dioulasso 01 | |
Congo, The Democratic Republic of the | Kinshasa School of Public Health | Kinshasa | |
Gambia | MRC Unit The Gambia at LSHTM | Fajara | Banjul |
Guinea | Centre National de Formation et de Recherche en Santé Rurale de Mafèrinyah | Conakry | |
Niger | Epicentre Niger | Niamey | |
Nigeria | Centre for Malaria and Other Tropical Diseases (CEMTROD) | Ilorin | Kwara State |
Rwanda | College of Medicine and Health Sciences, University of Rwanda | Kigali | |
Tanzania | National Institute For Medical Research (NIMR), Tanga Medical Research Centre | Tanga |
Lead Sponsor | Collaborator |
---|---|
University of Oxford | Mahidol Oxford Tropical Medicine Research Unit |
Burkina Faso, Congo, The Democratic Republic of the, Gambia, Guinea, Niger, Nigeria, Rwanda, Tanzania,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Other | Comparison of 63-day vs 42-day PCR corrected and uncorrected efficacy | Comparison of 63-day vs 42-day PCR corrected and uncorrected efficacy of ACTs vs TACTs | 63 days | |
Other | Proportions of recurrent infections | Proportions of recurrent infections with parasites carrying mutations of known functional significance | 63 days | |
Other | Proportions of specimens collected at baseline with parasites carrying mutations | Proportions of specimens collected at baseline with parasites carrying mutations of known functional or operational significance (pfkelch13, pfcrt, pfmdr1, pfdhfr, pfdhps, pfplasmepsin2 , partial or complete deletions of pfhrp2 and other current parasite genetic markers associated with resistance or identified over the course of the study) | baseline | |
Other | Candidate markers of resistance | Candidate markers of resistance identified through genome wide association studies with in vivo or in vitro parasite drug sensitivity phenotypes | 63 days | |
Other | 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 | 63 days. | |
Other | Accuracy of SNPs assessment | Accuracy of SNPs assessment from dry blood spots versus from whole genome sequencing in leukocyte depleted blood samples | 63 days. | |
Other | Correlation between qPCR based versus microscopy based assessments of parasite clearance dynamics | 14 days | ||
Other | Correlation of parasite clearance metrics as assessed by microscopy versus digital microscopy | 3 days | ||
Other | Comparison of transcriptomic patterns of drug sensitive and resistant parasites | Comparison of transcriptomic patterns of drug sensitive and resistant parasites before treatment and 6, 12 and 24 hours after start of treatment | 63 days | |
Other | 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 | 14 days | |
Other | Correlation between the host genotype and the pharmacokinetics and pharmacodynamics of antimalarials. | Host genotype (e.g., CYP2D6, CYP3A4, KCNQ1/LQT1, KCNH2/LQT2, SCN5A/LQT3) | 42 days | |
Other | Correlations between the place of residence, work, recent travel history | Correlations between the place of residence, work, recent travel history assessed by interview and mobile phone records to identify behaviours and risk factors associated with malaria infection. | 63 days | |
Other | Correlation between titres of antibodies against malaria parasite antigens and - efficacy defined as PCR corrected adequate clinical and parasitological response (ACPR) - efficacy defined as adequate clinical and parasitological response (ACPR) | 63 days | ||
Primary | 42 days Efficacy defined as PCR corrected adequate clinical and parasitological response (ACPR). | 42 days Efficacy defined as PCR corrected adequate clinical and parasitological response (ACPR). | 42 days | |
Secondary | 63-day PCR corrected and uncorrected efficacy | 63 days | ||
Secondary | 42-day PCR uncorrected efficacy | 42 days | ||
Secondary | Parasite clearance half-life | Assessed by microscopy as primary parameter to determine parasite clearance | 3 Days | |
Secondary | Proportion of subjects with microscopically detectable P. falciparum parasitaemia | Day 3 | ||
Secondary | Fever clearance time | fever clearance time (i.e. the time taken for the tympanic temperature to fall below 37.5 ºC) | 63 Days | |
Secondary | Proportion of subjects with gametocytaemia | proportion of subjects with gametocytaemia during and after treatment stratified by presence of gametocytes at enrolment | 63 Days | |
Secondary | Incidence of adverse events | including markers of hepatic, renal or bone marrow toxicity; cardiotoxicity | 42 days | |
Secondary | Incidence of serious adverse events | including markers of hepatic, renal or bone marrow toxicity; cardiotoxicity | 42 days | |
Secondary | Number of cardiotoxicity events | In particular QT or QTc-interval above 500 ms at timepoint H4 and H52/H64 and between these time points | 52 or 64 hours depends on treatment arm | |
Secondary | Change in haemoglobin stratified for G6PD status/genotype | 28 days | ||
Secondary | Proportion of subjects requiring retreatment due to vomiting | Proportion of subjects requiring retreatment due to vomiting within 1 hour after administration of the study drugs | 1 hour | |
Secondary | Proportion of subjects that reports completing a full course of observed TACT | 3 days | ||
Secondary | Proportion of subjects that reports completing a full course of observed ACT | 3 days | ||
Secondary | proportion of subjects 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. | 42 days | ||
Secondary | Pharmacokinetic profiles | including Cmax and AUC) of artemisinin-derivatives and partner drugs in ACT and TACT treated subjects in correlation with pharmacodynamics measures of drug efficacy | 42 days | |
Secondary | Pharmacokinetic interactions | including Cmax and AUC) of artemisinin-derivatives and partner drugs in ACT and TACT treated subjects in correlation with pharmacodynamics measures of drug efficacy | 42 days | |
Secondary | Plasma levels of partner drugs | Plasma levels of partner drugs in correlation with treatment efficacy and treatment arm | 7 days |
Status | Clinical Trial | Phase | |
---|---|---|---|
Completed |
NCT03939104 -
A Trial to Compare the Efficacy, Safety and Tolerability of Combinations of 3 Anti-malarial Drugs Against Combinations of 2 Anti-malarial Drugs (Asia)
|
Phase 3 |