Efficacy and Safety of Pyronaridine-Artesunate Versus Artemether-Lumefantrine

NCT ID: NCT05192265

Last Updated: 2022-04-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 172 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-05-20
• Study Completion Date: 2020-12-23

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.

Conditions

Malaria Fever; Plasmodium Falciparum Malaria; Uncomplicated Malaria

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Pyramax™

Artesunate-pyronaridine is indicated for the blood-stage treatment of the two dominant strains of malaria: P. falciparum and P. vivax. The medicine is also available in a child-friendly granule formulation to enhance palatability in this vulnerable population. Dosing was administered according to body weight: 5 - \<8kg - one sachet daily for 3 days; 8 - \<15Kg - two sachets daily for 3 days; 15 - \<20 Kg - three sachets daily for 3 days; 20 - \<24 Kg - one tablet daily for 3 days; and 24 - \<45 Kg - two tablets daily for 3 days.

Group Type: EXPERIMENTAL

Antimalarials, pyronaridine-artesunate

Intervention Type: DRUG

The main interventions investigated are pyronaridine-artesunate granules or tablets (Pyramax™) manufactured by Shin Poong Pharmaceuticals, Seoul, Korea. Pyramax granules come in sachets with each containing 60mg of pyronaridine/20mg of artesunate while Pyramax tablets contain 180mg pyronaridine/60mg artesunate.

Coartem™

We used the standard six-dose regimen of artemether-lumefantrine dispersible tablets twice daily according to body weights. Each dispersible tablet contains 20mg of artemether/120mg of lumefantrine) and the patients were dosed as follows: 5 -<15Kg one tablet, 15 - <25 Kg two tablets, 25 - <35 Kg three tablets, and ≥35 Kg four tablets at the following dosing intervals:

• 0 hour - 1st dose;
• 8 hours - 2nd dose;
• 24 hours - 3rd dose;
• 36 hours - 4th dose;
• 48 hours - 5th dose
• 60 hours - 6th dose.

Group Type: ACTIVE_COMPARATOR

Antimalarials, Artemether + Lumefantrine

Intervention Type: DRUG

Artemether-lumefantrine dispersible tablets (Coartem™, Novartis pharma) twice daily according to body weights. Each dispersible tablet of AL contains 20mg of artemether/120mg of lumefantrine).

Interventions

Antimalarials, pyronaridine-artesunate

The main interventions investigated are pyronaridine-artesunate granules or tablets (Pyramax™) manufactured by Shin Poong Pharmaceuticals, Seoul, Korea. Pyramax granules come in sachets with each containing 60mg of pyronaridine/20mg of artesunate while Pyramax tablets contain 180mg pyronaridine/60mg artesunate.

Intervention Type: DRUG

Antimalarials, Artemether + Lumefantrine

Artemether-lumefantrine dispersible tablets (Coartem™, Novartis pharma) twice daily according to body weights. Each dispersible tablet of AL contains 20mg of artemether/120mg of lumefantrine).

Intervention Type: DRUG

Other Intervention Names

Pyramax™; Coartem™, Novartis pharma

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

• Minimum Eligible Age: 3 Months
• Maximum Eligible Age: 144 Months
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shin Poong Pharm Co Ltd 161 yoksam-ro, Gangnam-Gu Seoul 135-925, Korea

UNKNOWN

Sponsor Role: collaborator

Institute for Advanced Medical Research and Training, University of Ibadan, Ibadan

UNKNOWN

Sponsor Role: collaborator

University of Ibadan

OTHER

Sponsor Role: lead

Responsible Party

Adebola E. Orimadegun

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Catherine O Falade, MB.BS, MSc, FMCP, FWACP, MD

Role: PRINCIPAL_INVESTIGATOR

University of Ibadan; Consultant Clinical Pharmacologist, University College Hospital, Ibadan

Locations

Ikeoluwapo O Ajayi

Ibadan, Oyo State, Nigeria

Countries

Nigeria

References

Falade CO, Orimadegun AE, Olusola FI, Michael OS, Anjorin OE, Funwei RI, Adedapo AD, Olusanya AL, Orimadegun BE, Mokuolu OA. Efficacy and safety of pyronaridine-artesunate versus artemether-lumefantrine in the treatment of acute uncomplicated malaria in children in South-West Nigeria: an open-labelled randomized controlled trial. Malar J. 2023 May 13;22(1):154. doi: 10.1186/s12936-023-04574-7.

Reference Type: DERIVED

PMID: 37179349 (View on PubMed)

Provided Documents

Document Type: Study Protocol, Statistical Analysis Plan, and Informed Consent Form

View Document

Other Identifiers

UI/EC/19/0114

Identifier Type: -

Identifier Source: org_study_id