None listed
Conditions
Brief summary
Pyronaridine-artesunate is the most current efficacy of antimalarial drugs that has been used in some countries in Asia as Cambodia, Thailand… Pyronaridine-artesunate is a newer artemisinin combination therapy, and was recently approved by the European Medicine Agency for single time use in adults and children >20 kg in countries with documented artemisinin resistance. We here propose an open-labelled clinical trial to assess the efficacy and safety of pyronaridine-artesunate for the treatment of uncomplicated falciparum malaria or mixed infection in Khanh Hoa, Dak Nong, Binh Phuoc, Ninh Thuan and Gia Lai provinces in Central and Southern Viet Nam. Interventional study for the assessment of drug efficacy and safety over 42 days Patients with acute uncomplicated P. falciparum malaria. Samples size: 170.patients. The patients respond all Inclusion and exclusion criteria will be recruited into study. Pyronaridine-artesunate tablet (Pyramax®). One tablet contains 60mg artesunate+ 180mg pyronaridine. Dosing will be according to body weight. Pyronaridine-artesunate will be taken orally with water, once daily for 3 days. The patients will be assessed therapy efficacy and safety for 42 days All patients will have a blood smear examined every 12 hours from D0 – D3 or 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. The primary endpoint of the study is day 42 PCR corrected ACPR ( Adequate clinical and parasitological response. It means: absence of parasitaemia on day 42, irrespective of axillary temperature, in patients who did not previously meet any of the criteria of early treatment failure, late clinical failure or late parasitological failure) . To assess therapeutic efficacy of pyronaridine - artesunatefor the treatment of uncomplicated falciparum malaria in an area where artemisinin resistant malaria is prevalent. The secondary endpoints • The numbers of patients with a positive malaria slide 72 hours after treatment initiation • Fever clearance time, parasite clearance time. • Kaplan Meier analysis over 42 days for recrudescence and reinfections. • PCR uncorrected ACPR at 28 days or 42 days for P. falciparum infection.. • Gametocyte carriage rates and gametocyte clearance times. • Documented AEs and SAEs and relationships to study drugs.
Interventions
To assess the therapeutic efficacy of pyronaridine-artesunate (Pyramax®) tablets 180mg/60mg
a) the dose administered:
Body weight (kg) Daily dose (mg) Number of tablets
PYR AS
20 - < 24 180 60 1
24 - < 45 360 120 2
45 - < 65 540 180 3
> 65 720 240 4
b) the duration of administration :
To assess the therapeutic efficacy of pyronaridine-artesunate (Pyramax®) tablets 180mg/60mg a) the dose administered: Body weight (kg) Daily dose (mg) Number of tablets PYR AS 20 - < 24 180 60 1 24 - < 45 360 120 2 45 - < 65 540 180 3 > 65 720 240 4 b) the duration of administration : 3 days. c) Pyronaridine- artesunate will be taken orally with water, once daily for 3 days. Each dose will be administered under supervision in the clinic or if not possible by a home visitor to the patient’s home. A dose will be repeated in full if vomiting occurs within 30 minutes of administration of the first day of administration only. This event will be documented in the case record form (CRF).
Sponsors
Ministry of Health, Viet Nam
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
7 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
• Adults less than or equal to 70 and children greater than or equal to 7 year old and greater than or equal to 20 kbw • 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, parasite density greater than or equal to' 1000 and below 150 000/asexual per micro liter • Microscopic confirmation of asexual stages of P.falciparum (mono P. falciparum infection ) • 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
• Children < 7 year old and < 20 kbw and Adults > 70 year old. • Pregnancy or lactation (urine test for ß HCG to be performed on any woman of child bearing age that is 18 to 45 years). • Unmarried female aged 12-18 years • Signs or symptoms indicative of severe malaria: • Impaired consciousness (Blantyre Coma Score <5) • Severe anaemia (Hct<20 % or Hb < 8g/dl) • Bleeding disorder –evidenced by epistaxis, bleeding gums, frank haematuria, bleeding from venepuncture sites • Respiratory, Kidney distress • Severe jaundice • Known hypersensitivity to artemisinins - defined as history of erythroderma/other severe cutaneous reaction, angioedema or anaphylaxis to pyronaridine • History of splenectomy • Known history or evidence of clinically significant liver 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 test (AST and ALT levels) more than 2.5 times the upper limit of normal range. • Total Bilirubin > 2 ULN
Outcome results
None listed