Malaria, Falciparum
Conditions
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).
Interventions
Sponsors
NCHADS - Ministry of Health of Cambodia
University of Oxford
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
7 Years to No maximum
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| result of PCR | 42 day |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| eosinophil count | at day 0, 3, 7 and day 28 | — |
| K13 and pfmdr1 of P falciparum resistance | at day 0, 3, 7 and day 28 | — |
| numbers of patients with a positive malaria slide 72 hours after treatment initiation | 72 hours | — |
| fever clearance time | 24 hours | the time taken for tympanic temperature to fall below 37.5˚C and remain there for at least 24 hours |
| hepatic biological values | at day 0, 3,7 and day 28 | the hepatic biological values will be measured which are AST,ALT,albumin and total bilirubin |
| PCR uncorrected ACPR | at 28 days or 42 days | PCR uncorrected ACPR at 28 days or 42 days for P. falciparum, P. falciparum and mixed infections in Pailin |
| PCR corrected ACPR | at 28 days and 42 days | PCR corrected ACPR at 28 days or for P. falciparum, P. vivax and mixed infections and at 42 days for P. falciparum and mixed infections |
| Gametocyte carriage rates | at day 0, 3, 7 day 28 | — |
| gametocyte clearance times | at day 0, 3, 7 and day28 | — |
| Number of patient with reinfection and recrudescences | over 42 days | — |
Countries
Cambodia
Outcome results
None listed