The Efficacy and Safety of Pyronaridine-artesunate Combined With Low Dose Primaquine for Preventing Transmission of P. Falciparum Gametocytes in Sub-Saharan Africa
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Enrollment
- 100
- Locations
- 2
- Primary Endpoint
- Change in mosquito infectivity assessed through membrane feeding assays (day 2)
Study Overview
Brief Summary
The purpose of this study is to assess the gametocytocidal and transmission reducing activity of pyronaridine-artesunate (PA) and dihydroartemisinin-piperaquine (DP) with and without a single low dose of primaquine (PQ; 0.25mg/kg). Outcome measures will include infectivity at 2 and 7 days after treatment, the duration of infectivity in the artemisinin combination therapy (ACT) only arms, and the production and detectability of histidine rich protein II.
Detailed Description
Protocol will be shared on request
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Single (Outcomes Assessor)
Masking Description
This is a single blind randomised controlled trial. The treating physician and staff involved with assessing all laboratory outcomes of the study are blinded, but no placebo will be used. The study pharmacist will be unblinded and responsible for randomisation and treatment administration.
Eligibility Criteria
- Ages
- 5 Years to 50 Years (Child, Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Age ≥ 5 years and ≤ 50 years
- •Absence of symptomatic falciparum malaria, defined by fever on enrolment
- •Presence of ≥16 gametocytes/µL (i.e. ≥1 gametocytes recorded in the thick film against 500 white blood cells)
- •No allergies to study drugs
- •Use of antimalarial drugs over the past 7 days (as reported by the participant)
- •Hemoglobin ≥ 9.5 g/dL
- •Individuals weighing >< 80 kg
- •No evidence of severe or chronic disease
- •Written, informed consent
Exclusion Criteria
- •Age < 5 years or > 50 years
- •Pregnancy
- •Previous reaction to study drugs/known allergy to study drugs
- •Signs of severe malaria
- •Taking drugs which may be metabolized by cytochrome enzyme CYP2D6 (e.g., flecainide, metoprolol, imipramine, amitriptyline, clomipramine)
- •Blood transfusion within the last 90 days
- •Patients with clinical signs or symptoms of hepatic injury (such as nausea and/or abdominal pain associated with jaundice) or known severe liver disease (i.e. decompensated cirrhosis, Child-Pugh stage B or C).
- •Patients with clinical signs or symptoms of renal impairment or known renal impairment
- •Family history of congenital prolongation of the QTc interval or sudden death or with any other clinical condition known to prolong the QTc interval such as history of symptomatic cardiac arrhythmias, with clinically relevant bradycardia or with severe cardiac disease.
- •Taking drugs that are known to influence cardiac function and to prolong QTc interval, such as class IA and III: neuroleptics, antidepressant agents, certain antibiotics including some agents of the following classes - macrolides, fluoroquinolones, imidazole, and triazole antifungal agents, certain non-sedating antihistaminics (terfenadine, astemizole) and cisapride.
- •Consent not given
Arms & Interventions
Pyronaridine-artesunate (PA)
Subjects will receive pyronaridine-artesunate (PA) once daily for 3 days.
Intervention: Pyronaridine Tetraphosphate/Artesunate (Drug)
PA with single low dose primaquine (PQ)
Subjects will receive pyronaridine-artesunate (PA) once daily for 3 days, and a low dose of primaquine (PQ) on the first dat of treatment. PQ dose is at the World Health Organization (WHO) recommended dose of 0.25 mg/kg.
Intervention: Pyronaridine Tetraphosphate/Artesunate (Drug)
PA with single low dose primaquine (PQ)
Subjects will receive pyronaridine-artesunate (PA) once daily for 3 days, and a low dose of primaquine (PQ) on the first dat of treatment. PQ dose is at the World Health Organization (WHO) recommended dose of 0.25 mg/kg.
Intervention: Primaquine Diphosphate (Drug)
Dihydroartemisinin-piperaquine (DP)
Subjects will receive dihydroartemisinin-piperaquine (DP) once daily for 3 days.
Intervention: Dihydroartemisinin/Piperaquine (Drug)
DP with single low dose primaquine (PQ)
Subjects will receive dihydroartemisinin-piperaquine (DP) once daily for 3 days., and a low dose of primaquine (PQ) on the first dat of treatment. PQ dose is at the World Health Organization (WHO) recommended dose of 0.25 mg/kg.
Intervention: Dihydroartemisinin/Piperaquine (Drug)
DP with single low dose primaquine (PQ)
Subjects will receive dihydroartemisinin-piperaquine (DP) once daily for 3 days., and a low dose of primaquine (PQ) on the first dat of treatment. PQ dose is at the World Health Organization (WHO) recommended dose of 0.25 mg/kg.
Intervention: Primaquine Diphosphate (Drug)
Outcomes
Primary Outcomes
Change in mosquito infectivity assessed through membrane feeding assays (day 2)
Time Frame: 2 days (day 0 & 2)
The proportion of mosquitoes infected, assessed through membrane feeding and measured as oocyst prevalence in mosquitoes dissected on day 2 post feed, compared to baseline
Secondary Outcomes
- Histidine rich protein 2 (HRP2) area under the curve (AUC)(11 days)
- Duration of infectivity(5-10 days (as described))
- Mosquito infectivity assessed through membrane feeding assays - inter arm(3 days (day 0, 2 & 7))
- Histidine rich protein 2 (HRP2) concentration(11 days)
- Rapid diagnostic test result(11 days)
- Gametocyte under the curve (AUC)(11 days)
- Asexual parasite area under the curve (AUC)(11 days)
- Asexual parasite prevalence(11 days)
- Asexual parasite circulation time(11 days)
- Parasite genotype(1 day)
- Change in mosquito infectivity assessed through membrane feeding assays (day 7)(2 days (day 0 & 7))
- Gametocyte density(11 days)
- Haemoglobin level(11 days)
- Histidine rich protein 2 (HRP2) circulation time(11 days)
- Gametocyte sex ratio(11 days)
- Histidine rich protein gene deletion(1 day)
- Area under the curve (AUC) of infectivity/time(5-10 days (as described))
- Gametocyte circulation time(11 days)
- Gametocyte prevalence(11 days)
- Asexual parasite density(11 days)