Clinical trial NCT04049916: Pyronaridine-artesunate With Low Dose Primaquine for Preventing P. Falciparum Transmission
Official title: The Efficacy and Safety of Pyronaridine-artesunate Combined With Low Dose Primaquine for Preventing Transmission of P. Falciparum Gametocytes in Sub-Saharan Africa
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Malaria,Falciparum
Keywords: Primaquine
Pyramax
Euartesim
Dihydroartemisinin-piperaquine
Pyronaridine-artesunate
Lead sponsor: London School of Hygiene and Tropical Medicine
Sponsor class: OTHER
Collaborators: name: Malaria Research and Training Center, Bamako, Mali
name: Radboud University Medical Center
First posted: 2019-08-08
Enrollment: 100
Sex: ALL
Minimum age (years): 5
Maximum age (years): 50
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Eligibility criteria: 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

Primary outcomes:
measure: Change in mosquito infectivity assessed through membrane feeding assays (day 2)
timeFrame: 2 days (day 0 & 2)
Secondary outcomes:
measure: Change in mosquito infectivity assessed through membrane feeding assays (day 7)
timeFrame: 2 days (day 0 & 7)
measure: Mosquito infectivity assessed through membrane feeding assays - inter arm
timeFrame: 3 days (day 0, 2 & 7)
measure: Duration of infectivity
timeFrame: 5-10 days (as described)
measure: Area under the curve (AUC) of infectivity/time
timeFrame: 5-10 days (as described)
measure: Haemoglobin level
timeFrame: 11 days
measure: Histidine rich protein 2 (HRP2) concentration
timeFrame: 11 days
measure: Histidine rich protein 2 (HRP2) circulation time
timeFrame: 11 days
measure: Histidine rich protein 2 (HRP2) area under the curve (AUC)
timeFrame: 11 days
measure: Rapid diagnostic test result
timeFrame: 11 days
measure: Gametocyte density
timeFrame: 11 days
measure: Gametocyte under the curve (AUC)
timeFrame: 11 days
measure: Gametocyte prevalence
timeFrame: 11 days
measure: Gametocyte circulation time
timeFrame: 11 days
measure: Gametocyte sex ratio
timeFrame: 11 days
measure: Asexual parasite density
timeFrame: 11 days
measure: Asexual parasite area under the curve (AUC)
timeFrame: 11 days
measure: Asexual parasite prevalence
timeFrame: 11 days
measure: Asexual parasite circulation time
timeFrame: 11 days
measure: Parasite genotype
timeFrame: 1 day
measure: Histidine rich protein gene deletion
timeFrame: 1 day
Other outcomes:
Locations:
city: Bamako
country: Mali
facility: Malaria Research and Training Centre
city: Nijmegen
country: Netherlands
facility: Radboud university medical center
Study officials:
References:
citation: Stone W, Mahamar A, Sanogo K, Sinaba Y, Niambele SM, Sacko A, Keita S, Youssouf A, Diallo M, Soumare HM, Kaur H, Lanke K, Ter Heine R, Bradley J, Issiaka D, Diawara H, Traore SF, Bousema T, Drakeley C, Dicko A. Pyronaridine-artesunate or dihydroartemisinin-piperaquine combined with single low-dose primaquine to prevent Plasmodium falciparum malaria transmission in Ouelessebougou, Mali: a four-arm, single-blind, phase 2/3, randomised trial. Lancet Microbe. 2022 Jan;3(1):e41-e51. doi: 10.1016/S2666-5247(21)00192-0.