Study of resistance to artesunate of malaria parasite
| ISRCTN | ISRCTN64835265 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN64835265 |
| Secondary identifying numbers | Version 12 Dec 2007 |
- Submission date
- 22/01/2008
- Registration date
- 25/01/2008
- Last edited
- 21/03/2013
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Infections and Infestations
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Plain English summary of protocol
Not provided at time of registration
Contact information
Prof Francois Nosten
Scientific
Scientific
Shoklo Malaria Research Unit (SMRU)
68/30 Baan Tung Road
Mae Sot
63110
Thailand
| Phone | +66 (0)55 545 021 |
|---|---|
| SMRU@tropmedres.ac |
Study information
| Study design | Pharmacokinetic and dynamic study of artesunate in two randomly assigned treatment groups. |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Non randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details below to request a patient information sheet. |
| Scientific title | Clinical investigation of in-vivo and in vitro susceptibility of P. falciparum to artesunate in Western Thailand |
| Study objectives | Has the resistance to artemisinins in P. falciparum emerged in Thailand? |
| Ethics approval(s) | Ethics approval received from Mahidol University Ethical Committee on the 20th December 2007 (ref: MUTM 2007-130). |
| Health condition(s) or problem(s) studied | Malaria/uncomplicated/resistance |
| Intervention | Patients will be randomised in blocks of 10 to receive either: 1. Artesunate (Guilin Pharmaceutical Company, PRC) orally (po) 2 mg/kg/day for 7 days 2. Artesunate (Guilin Pharmaceutical Company, PRC) po 4 mg/kg/day for 3 days plus mefloquine 15 mg/kg on day 3 and 10 mg/kg on day 4 On enrolment a detailed history and full clinical examination will be performed and recorded on a standard Case Report Form (CRF). The patient will then be weighed. A Teflon® heparinised sampling catheter will be inserted in a forearm vein. Baseline blood samples will be taken as described below. Part of the blood sample will be taken at baseline for immediate culture (for an in-vitro susceptibility test) and also storage of parasites (cryopreserved in liquid nitrogen), parasite deoxyribonucleic acid [DNA] and messenger ribonucleic acid [mRNA]. On admission 5 ml blood will be collected for parasite count (thin and thick films stained by Giemsa's method), and routine biochemistry (sodium, potassium, chloride, calcium, blood urea nitrogen, creatinine, total bilirubin, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, albumin, total protein, glucose and total carbon dioxide) and haematology (haematocrit, haemoglobin, white blood cell count with differentiation, platelets). An additional 5 ml of blood will be collected in a sterile heparinised tube for parasite culture and cryopreservation, and 2 ml for assessment of drug levels (artesunate and mefloquine). The total amount of blood taken for study purposes will be 12 ml on admission and about 10 to 20 ml during follow-up (dependent on the parasite clearance time; blood collection for parasitaemia during hospitalisation will stop when the patient is parasite negative). Sampling (2 ml): 1. Parasite counts: 0, 4, 8, 12, 18, 24 hours then 6 hourly until parasite clearance 2. Drug levels: plasma samples will be taken. Most are fixed times but for artesunate there is a population PK component so random times within time-bins are proposed. In children capillary whole blood sampling for mefloquine may need to be substituted. Patients will remain in hospital for 7 days or longer if parasites have not cleared. They will then be followed up to Day 63 and at each weekly visit will have a haematocrit and parasite count checked. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Not Specified |
| Drug / device / biological / vaccine name(s) | Artesunate |
| Primary outcome measure | A population based pharmacokinetic-pharmacodynamic modelling approach will be used to describe the antimalarial effect of artesunate in patients with acute falciparum malaria. The objective of the modelling exercise is to characterise the relationship between pharmacokinetic variables (areas under curve [AUC], Cmax) and parasite clearance measures (parasite clearance time [PCT], parasite reduction ratio [PRR]), completed with in vitro susceptibility and molecular markers of resistance. |
| Secondary outcome measures | Parasitological efficacy |
| Overall study start date | 01/01/2008 |
| Completion date | 01/06/2008 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Sex | Both |
| Target number of participants | 40 |
| Key inclusion criteria | 1. 40 patients with uncomplicated falciparum malaria 2. Aged greater than or equal to 15 years, either sex 3. Symptomatic of malaria infection, i.e., history of fever or presence of fever greater than 37.5°C 4. Microscopic confirmation of asexual stages of P. falciparum with parasitaemia greater than 10,000/ml 5. Written informed consent to participate in trial |
| Key exclusion criteria | 1. Pregnancy or lactation (urine test for beta-human chorionic gonadotropin [β-HCG] to be performed on any woman of child bearing age unless menstruating) 2. P. falciparum asexual stage parasitaemia greater than or equal to 4% red blood cells (175,000/µl) 3. History of treatment with antimalarials (except chloroquine [CQ] or sulfadoxine-pyrimethamine [SP]) in the previous 48 hours 4. Microscopy indicates a mixed infection 5. Signs or symptoms indicative of severe malaria: 5.1. Impaired consciousness (Glasgow Coma Scale [GCS] less than 15) 5.2. Bleeding disorder (severe nosebleed, bleeding gums, frank haematuria, bleeding from venepuncture sites) 5.3. Respiratory distress (deep breathing or respiratory rate [RR] greater than 30) 5.4. Shock (circulatory collapse with systolic blood pressure [SBP] less than 80 mmHg) 5.5. Hyperparasitaemia (see above) 5.6. Acidosis (bicarbonate [HCO3-] less than 15 mmol/L) 5.7. Renal insufficiency (creatinine greater than 3 mg/dL) 5.8. Severe jaundice (total bilirubin greater than 2.5 mg/dL) 5.9. Severe anaemia (haematocrit [Hct] less than 20% in adults or less than 15% in children) 5.10. Severe hypoglycaemia (glucose less than 40 mg/dL) 6. Known hypersensitivity to artemisinin derivatives or mefloquine 7. History of convulsions or neuropsychiatric disorder 8. History of splenectomy |
| Date of first enrolment | 01/01/2008 |
| Date of final enrolment | 01/06/2008 |
Locations
Countries of recruitment
- Thailand
Study participating centre
Shoklo Malaria Research Unit (SMRU)
Mae Sot
63110
Thailand
63110
Thailand
Sponsor information
University of Oxford (UK)
University/education
University/education
Centre for Clinical Vaccinology and Tropical Medicine (CCVTM)
Churchill Hospital
Old Road
Headington
Oxford
OX3 7LJ
England
United Kingdom
| Phone | +44 (0)1865 857431 |
|---|---|
| paul.hogben@ndm.ox.ac.uk | |
| Website | http://www.ccvtm.ox.ac.uk/ |
"ROR" |
https://ror.org/052gg0110 |
Funders
Funder type
Charity
The Wellcome Trust South-East Asia (SEA) Programme (Thailand)
No information available
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | results | 30/07/2009 | Yes | No |
