Clinical trial NCT05192265: Efficacy and Safety of Pyronaridine-Artesunate Versus Artemether-Lumefantrine
Official title: Comparative Efficacy and Safety of Pyronaridine-Artesunate Versus Artemether-Lumefantrine in The Treatment of Acute Uncomplicated Malaria Among Children In South-West Nigeria
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Malaria Fever
Plasmodium Falciparum Malaria
Uncomplicated Malaria
Keywords: Antimalarial
Pyronaridine-artesunate
Artemether-lumefantrine
Lead sponsor: University of Ibadan
Sponsor class: OTHER
Collaborators: name: Shin Poong Pharm Co Ltd 161 yoksam-ro, Gangnam-Gu Seoul 135-925, Korea
name: Institute for Advanced Medical Research and Training, University of Ibadan, Ibadan
First posted: 2022-01-14
Enrollment: 172
Sex: ALL
Minimum age (years): 3
Maximum age (years): 144
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Study participants were assigned into one of the two treatment groups according to a pre-generated randomization code. Children randomized to Pyramax™ received three doses of pyronaridine-artesunate granules or tablets manufactured by Shin Poong Pharmaceuticals, Seoul, Korea depending on their body weights. Pyramax granules come in sachets with each containing 60mg of pyronaridine/20mg of artesunate while Pyramax tablets contain 180mg pyronaridine/60mg artesunate. Study participants randomized to Coartem™ received the standard six-dose regimen of AL dispersible tablets (Coartem™, Novartis pharma) twice daily according to body weights.
Primary purpose: TREATMENT

Brief summary: In Nigeria, malaria is the commonest reason for outpatient clinic attendance in childhood and is responsible for about 20% of childhood deaths. The emergence of strains of P. falciparum resistant to chloroquine and sulfadoxine-pyrimethamine led to severe worsening of morbidity and mortality from malaria. As a result of resistance to previously used monotherapy, the World Health Organization (WHO) in 2001, recommended that malaria-endemic countries experiencing drug-resistant malaria infection adopt combination therapy. Artemisinin-based combination therapy (ACT) is preferred to the non-ACT combination. In this randomized open-label clinical trial, the safety and efficacy of pyronaridine-artesunate and artemether-lumefantrine in the treatment of malaria among children aged 3 to 144 months who have microscopically confirmed symptomatic Plasmodium falciparum malaria were compared. The study was carried out at the Oni Memorial Children's Hospital, Ring Road Ibadan. One hundred and seventy-two children between 3 and 120 months who meet the inclusion criteria will be enrolled after obtaining written or witnessed signed informed consent from the parents or guardian. A detailed history and physical examination were carried out on each enrollee. Finger prick blood samples were taken from each enrolee for thick blood smear for malaria parasite, haematocrit, and blood spots on filter paper. Five millilitres of venous blood will be taken from an arm vein for baseline liver function tests, creatinine, and random blood glucose on days 0, 3, 7 and 28. Enrollees were randomized into one of two groups. Group one received pyronaridine-artesunate while group two received artemether-lumefantrine at standard doses. Enrollees were seen daily from days 0-3, and on days 7, 14, 21 and 28. Study drugs were administered supervised at standard dosage on days 0, 1, and 2. History taking, physical examination and blood smears were done at each contact time. Special attention will be paid to adverse effects. Parasite clearance time, fever clearance time and cure rates were compared between the two groups.


Eligibility criteria: Inclusion Criteria:

1. Individuals of either gender between the ages of 3months (but weight ≥5 kg) and 12 years who present with symptoms compatible with acute uncomplicated malaria
2. Minimum asexual parasite density of 1000/µl. This will be done at enrolment for all study participants.
3. Fever with an axillary temperature≥ 37.5°C or history of fever within 24hours of presentation
4. Residence within 15 kilometres to the study site.
5. Ability to take drugs orally.
6. Absence of history of ACT intake in the two weeks prior to enrolment
7. A signed informed consent from parents or guardians of the prospective enrollee to participate in the study

Exclusion Criteria:

1. History of allergy to study drugs i.e. artemisinins, lumefantrine and pyronaridine
2. Any concurrent illness that could hamper evaluation of response e.g. bacterial infections, viral infections, severe gastrointestinal disease, malnutrition (weight for height \<70%).
3. Presence of clinical evidence of severe malaria such as prostration, inability to drink or breastfeed, persistent vomiting, convulsion, severe anaemia haemoglobin \<5 g/dl), unarousable coma
4. Patients with known chronic diseases like chronic kidney disease, chronic liver disease, malnutrition, cardiac failure, Sickle Cell haemoglobin (HbSS) etc.
5. Mixed or mono-infection with another Plasmodium species detected by microscopy;
6. presence of severe malnutrition defined as a child aged between 6-60 months whose weight-for-high is below -3 z-score, or has symmetrical oedema involving at least the feet or has a mid-upper arm circumference \< 115 mm).
7. Parent or guardian who in the judgment of the investigator will not comply with protocol in the opinion of the investigator

Primary outcomes:
measure: PCR-adjusted adequate clinical and parasitological response (ACPR)
timeFrame: Treatment day 3 to 28
Secondary outcomes:
measure: Adequate clinical and parasitological response without correction for reinfection
timeFrame: day 28
measure: Parasite clearance time
timeFrame: Treatment day 0 to 28
measure: Fever clearance time
timeFrame: Treatment day 0 to 28
measure: Gametocyte carriage
timeFrame: Treatment day 0 to 28
Other outcomes:
Locations:
city: Ibadan
country: Nigeria
facility: Ikeoluwapo O Ajayi
state: Oyo
Study officials:
affiliation: University of Ibadan; Consultant Clinical Pharmacologist, University College Hospital, Ibadan
name: Catherine O Falade, MB.BS, MSc, FMCP, FWACP, MD
role: PRINCIPAL_INVESTIGATOR
References: