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Malaria FeverPhase 2/3NCT05192265

Efficacy and Safety of Pyronaridine-Artesunate Versus Artemether-Lumefantrine

A Phase 2/3 study testing Antimalarials, pyronaridine-artesunate and Antimalarials, Artemether + Lumefantrine in people with Malaria Fever and Plasmodium Falciparum Malaria, run by University of Ibadan at 1 site in Nigeria.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 3 to 144 months
What is being tested?
Antimalarials, pyronaridine-artesunate and Antimalarials, Artemether + Lumefantrine
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
172 participants
Where
1 siteNigeria
Study dates
20 May 2019to 23 Dec 2020
Phase
Phase 2/3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 3 to 144 months
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • 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
  • Minimum asexual parasite density of 1000/µl. This will be done at enrolment for all study participants.
  • Fever with an axillary temperature≥ 37.5°C or history of fever within 24hours of presentation
  • Residence within 15 kilometres to the study site.
  • Ability to take drugs orally.
  • Absence of history of ACT intake in the two weeks prior to enrolment
  • A signed informed consent from parents or guardians of the prospective enrollee to participate in the study

Who cannot join

  • History of allergy to study drugs i.e. artemisinins, lumefantrine and pyronaridine
  • Any concurrent illness that could hamper evaluation of response e.g. bacterial infections, viral infections, severe gastrointestinal disease, malnutrition (weight for height <70%).
  • 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
  • Patients with known chronic diseases like chronic kidney disease, chronic liver disease, malnutrition, cardiac failure, Sickle Cell haemoglobin (HbSS) etc.
  • Mixed or mono-infection with another Plasmodium species detected by microscopy;
  • 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).
  • Parent or guardian who in the judgment of the investigator will not comply with protocol in the opinion of the investigator

Trial locations and contacts

1 site in 1 country.

Nigeria1 site

  • Ikeoluwapo O Ajayi

    Ibadan, Oyo State, 200212

Other trials in Nigeria

About this study

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

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.

Being tested
Antimalarials, pyronaridine-artesunate, Antimalarials, Artemether + Lumefantrine
Keywords
Antimalarial, Pyronaridine-artesunate, Artemether-lumefantrine
Medical subject headings
Malaria, Malaria, Falciparum

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Antimalarials, pyronaridine-artesunateDrug

    Also called Pyramax™

    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.

  • Antimalarials, Artemether + LumefantrineDrug

    Also called Coartem™, Novartis pharma

    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).

Study groups in NCT05192265
Study groupRoleWhat they receive
Pyramax™ExperimentalArtesunate-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.
Receives: Drug: Antimalarials, pyronaridine-artesunate
Coartem™Active comparatorWe 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.
Receives: Drug: Antimalarials, Artemether + Lumefantrine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. PCR-adjusted adequate clinical and parasitological response (ACPR)

    Defined as absence of patent parasitaemia, regardless of axillary temperature and without evidence of previous treatment failure up to day 28.

    Measured: Treatment day 3 to 28

Secondary outcomes (4)

  1. Adequate clinical and parasitological response without correction for reinfection

    Adequate clinical and parasitological response (ACPR; absence of parasitaemia on day 28 without previously meeting criteria for ETF, LCF, or LPF).

    Note:

    ETF: Early treatment failure defined as danger signs or complicated malaria or failure to adequately respond to therapy on days 0-3.

    LCF: Late clinical failure defined as danger signs or complicated malaria or fever and parasitaemia on days 4-28 without previously meeting criteria for ETF or LPF.

    LPF: Late parasitological failure defined as asymptomatic parasitaemia on days 7-28 without previously meeting criteria for ETF or LCF.

    Measured: day 28

  2. Parasite clearance time

    Time from first dose of ACT until first total and continued disappearance of asexual parasite forms.

    Measured: Treatment day 0 to 28

  3. Fever clearance time

    Time from first dose until the first time the body temperature (for those with a raised temperature at enrolment) decrease to below 37.5 degree Celsius and remain so for at least 24 hours.

    Measured: Treatment day 0 to 28

  4. Gametocyte carriage

    Proportions of patients with gametocyte at a given point in time.

    Measured: Treatment day 0 to 28

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Jan 2022
  2. Study start20 May 2019
  3. Primary completion23 Dec 2020
  4. Study completion23 Dec 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
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.
Masking
None (open label)
Enrolment
172 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05192265
Sponsor's protocol ID
UI/EC/19/0114
Status last verified
Mar 2022
First submitted
21 Dec 2021
Last updated
7 Apr 2022
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 37179349

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Antimalarials, pyronaridine-artesunate and Antimalarials, Artemether + Lumefantrine in people with Malaria Fever and Plasmodium Falciparum Malaria, run by University of Ibadan at 1 site in Nigeria.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 7 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Nigeria. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

PCR-adjusted adequate clinical and parasitological response (ACPR) (time frame: Treatment day 3 to 28). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05192265, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Apr 2022.

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