Clinical trial NCT03201770: Cohort Event Monitoring Study of Pyramax®
Official title: Phase IIIb/IV Cohort Event Monitoring Study To Evaluate, In Real Life Setting, The Safety And Tolerability In Malaria Patients Of The Fixed-Dose Artemisinin-Based Combination Therapy Pyramax®
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Malaria,Falciparum
Keywords: Uncomplicated Malaria
Pyramax
Pyronaridine artesunate
Lead sponsor: Shin Poong Pharmaceutical Co. Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Medicines for Malaria Venture
First posted: 2017-06-28
Enrollment: 8572
Sex: ALL
Minimum age (years): 3
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The study is to be performed in public health facilities in Central and West Africa where Pyramax will be used as treatment of uncomplicated malaria episodes, including repeat episodes. The study is to assess the safety of Pyramax, particularly in patients with underlying liver function abnormalities, in patients who have co-morbid conditions, such as HIV, and also in very small children (\<1 year of age).

Detailed description: This is a non-comparative Cohort Event Monitoring study. The study will assess the safety of Pyramax in terms of the evaluation and identification of the hepatic safety events in a sub group of patients enrolled with liver function tests (LFT)s \>2x upper limit of normal (ULN) from blood taken immediately prior to treatment without any clinical signs or symptoms of hepatotoxicity and with signs and symptoms of uncomplicated malaria confirmed by a Rapid Diagnostic Test (RDT) or microscopy (thick blood smear). The study will compare the clinical hepatic safety of Pyramax between a cohort of patients enrolled with LFTs \>2xULN and a cohort of patients enrolled with normal LFTs matched for demographic characteristics.

An estimated 8,572 malaria episodes are to be recruited to provide 120 malaria episodes in patients with baseline raised LFTs \>2xULN for follow up of liver function. A cohort of at least 2% of children who are \<1 year of age will be included for monitoring of liver function.

Eligibility criteria: Inclusion Criteria:

* Uncomplicated malaria (Plasmodia of any species) diagnosed as per national policies and in line with WHO recommendations:

  * Fever or history of fever in the previous 24 h and/or the presence of anaemia, for which pallor of the palms appears to be the most reliable sign in young children.
  * Confirmation of malaria by a parasitological diagnosis (RDT or Microscopy (thick blood smear). analysis).
* Weight ≥5 kg - \< 20 kg (granules); ≥20 kg (tablets).
* Ability to take an oral medication.
* Ability and willingness to participate based on signed informed consent (a parent or a guardian has to sign for children below 18 years old) and on signed assent form for minors that could be required per national regulations in each participating country.
* The patient has to comply with all scheduled follow-up visits.

Exclusion Criteria:

* Patients with clinical signs or symptoms of hepatic injury (such as nausea, abdominal pain associated with jaundice) or known severe liver disease (i.e. decompensated cirrhosis, Child-Pugh stage 3 or 4).
* Known allergy to artemisinin and/or to pyronaridine.
* Known pregnancy.
* Lactating women should be excluded if other anti-malarial treatments are available.
* Complicated malaria as per WHO definition (Annex 2)
* Patients that the investigator considers would be at particular risk if receiving an anti-malarial or if participating in the study.
* Patients having been treated with Pyramax in the previous 28 days.

Primary outcomes:
measure: Evaluation and identification of hepatic safety events, including raised liver function tests
timeFrame: Assessment up to Day 28.
Secondary outcomes:
measure: Overall safety
timeFrame: Assessment up to Day 28.
measure: Evaluation of Efficacy
timeFrame: Assessment up to Day 28.
Other outcomes:
Locations:
city: Yaoundé
country: Cameroon
facility: The Biotechnology Center Nkolbisson, Univ of Yaounde I, Messa
city: Kinshasa
country: Congo, The Democratic Republic of the
facility: Centre de Recherche du Centre Hospitalier du Mont Amba
city: Brazzaville
country: Congo
facility: Centre de Santé FCRM, Hospital of Talangai
city: Bouaké
country: Côte D'Ivoire
facility: Institut Pierre Richet / Institut National de SanPublique (IPR/INSP)
city: Lambaréné
country: Gabon
facility: CERMEL, Albert Schweitzer Hospital
Study officials:
affiliation: CERMEL, University of Tübingen, Germany
name: Michael Ramharter, MD, DTM&H
role: PRINCIPAL_INVESTIGATOR
References:
citation: Koehne E, Zander N, Rodi M, Held J, Hoffmann W, Zoleko-Manego R, Ramharter M, Mombo-Ngoma G, Kremsner PG, Kreidenweiss A. Evidence for in vitro and in vivo activity of the antimalarial pyronaridine against Schistosoma. PLoS Negl Trop Dis. 2021 Jun 24;15(6):e0009511. doi: 10.1371/journal.pntd.0009511. eCollection 2021 Jun.
citation: Tona Lutete G, Mombo-Ngoma G, Assi SB, Bigoga JD, Koukouikila-Koussounda F, Ntamabyaliro NY, Ntoumi F, Agnandji ST, Groger M, Shin J, Borghini-Fuhrer I, Arbe-Barnes S, Allen SJ, Kremsner PG, Miller R, Duparc S, Ramharter M; CANTAM study group. Pyronaridine-artesunate real-world safety, tolerability, and effectiveness in malaria patients in 5 African countries: A single-arm, open-label, cohort event monitoring study. PLoS Med. 2021 Jun 15;18(6):e1003669. doi: 10.1371/journal.pmed.1003669. eCollection 2021 Jun.