Clinical trial NCT02389439: Efficacy and Safety of Pyronaridine-artesunate for the Treatment in Uncomplicated Falciparum Malaria
Official title: Monitoring and Evaluation of the Therapeutic Efficacy and Safety of Pyronaridine-artesunate for the Treatment of Uncomplicated Falciparum Malaria in Western Cambodia, an Area of Artemisinin-resistant Falciparum Malaria
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Malaria, Falciparum
Lead sponsor: University of Oxford
Sponsor class: OTHER
Collaborators: name: NCHADS - Ministry of Health of Cambodia
First posted: 2015-03-17
Enrollment: 123
Sex: ALL
Minimum age (years): 7
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study is a prospective, single arm, open-labelled clinical trial. The total number subjects will be 145 patients to receive Pyronaridine-artesunate once daily for 3 days. Dosing will be according to the body weight.

All patients will have a blood smear examined daily during the first week by microscopy until parasite clearance (2 consecutive negative slides on two consecutive days; both asexual and sexual stages). A negative blood slide will be defined as parasite count negative per 1000 WBC in two consecutive days. The sample on day 3 will be taken as close as possible to 72h after the initial blood smear.

Participant will follow up for 42 days to assess the drug efficacy and safety (Day 7, 14, 21, 28, 35 and 42).


Eligibility criteria: Inclusion Criteria:

* Adults and children ≥ 20 kg
* Symptomatic of malaria infection, i.e. history of fever within 24 hours and/or presence of fever \>37.5°c.
* Microscopic confirmation of asexual stages of P. falciparum (P. falciparum and mixed infection in Pailin only)
* Capability of taking an oral medication
* Written informed consent given to participate in the trial
* Willingness and ability to adhere to follow-up visit schedule

Exclusion Criteria:

* Pregnancy or lactation (urine test for β HCG to be performed on any woman of child bearing age, that is 18 to 45 y/o)
* Female aged 12-18y
* Parasitemia \> 150 000/µL).
* Signs or symptoms indicative of severe malaria:

  * Impaired consciousness (Blantyre Coma Score \<5)
  * Severe anaemia (Hct\<15%)
  * Bleeding disorder -evidenced by epistaxis, bleeding gums, frank haematuria, bleeding from venepuncture sites
  * Respiratory distress
  * Severe jaundice
* Known hypersensitivity to artemisinins - defined as history of erythroderma/other severe cutaneous reaction, angioedema or to pyronaridine
* History of splenectomy
* Known history or evidence of clinically significant disorders, such as:

  * Known active Hepatitis A, e.g. by detection of anti HAV-IgM.
  * Known hepatitis B surface antigen (HBsAg) carrier.
  * Known hepatitis C antibody (HCV Ab).
  * Liver function tests (AST/ALT levels) more than 2.5 times the upper limit of normal range.

Primary outcomes:
measure: result of PCR
timeFrame: 42 day
Secondary outcomes:
measure: hepatic biological values
timeFrame: at day 0, 3,7 and day 28
measure: eosinophil count
timeFrame: at day 0, 3, 7 and day 28
measure: K13 and pfmdr1 of P falciparum resistance
timeFrame: at day 0, 3, 7 and day 28
measure: numbers of patients with a positive malaria slide 72 hours after treatment initiation
timeFrame: 72 hours
measure: fever clearance time
timeFrame: 24 hours
measure: Number of patient with reinfection and recrudescences
timeFrame: over 42 days
measure: PCR uncorrected ACPR
timeFrame: at 28 days or 42 days
measure: PCR corrected ACPR
timeFrame: at 28 days and 42 days
measure: Gametocyte carriage rates
timeFrame: at day 0, 3, 7 day 28
measure: gametocyte clearance times
timeFrame: at day 0, 3, 7 and day28
Other outcomes:
Locations:
city: Battambang
country: Cambodia
facility: Tasanh Health Centre, Battambang
city: Pailin
country: Cambodia
facility: Referral hospital (Pailin)
city: Pursat)
country: Cambodia
facility: Promoy Health Centre (Pursat)
Study officials:
References:
citation: Leang R, Canavati SE, Khim N, Vestergaard LS, Borghini Fuhrer I, Kim S, Denis MB, Heng P, Tol B, Huy R, Duparc S, Dondorp AM, Menard D, Ringwald P. Efficacy and Safety of Pyronaridine-Artesunate for Treatment of Uncomplicated Plasmodium falciparum Malaria in Western Cambodia. Antimicrob Agents Chemother. 2016 Jun 20;60(7):3884-90. doi: 10.1128/AAC.00039-16. Print 2016 Jul.