Pharmacokinetics and efficacy of dihydroartemisinin-piperaquine in the treatment of uncomplicated falciparum malaria in children in Burkina Faso

ISRCTN	ISRCTN59761234
DOI	https://doi.org/10.1186/ISRCTN59761234
Protocol serial number	N/A
Sponsor	Beijing Holley-Cotec Pharmaceuticals Co. Ltd (China)
Funders	Doris Duke Charitable Foundation (USA), Beijing Holley-Cotec Pharmaceuticals Co. Ltd (China), National Budget of Institut de Recherche en Science de la Sante (IRSS) (Burkina Faso)

Submission date: 11/09/2007
Registration date: 05/02/2008
Last edited: 13/05/2015

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

Shoklo Malaria Research Unit (SMRU)
P.O. Box 46
68/30 Baan Tung Road
Tak Province
Mae Sot
63110
Thailand

Study information

Primary study design	Interventional
Study design	1. Treatment efficacy: open-label trial 2. Population kinetic studies will use sparse capillary sampling
Secondary study design	Randomised controlled trial
Scientific title	Assessing the efficacy of Dihydroartemisinin-piperaquine in African patients suffering of uncomplicated falciparum malaria and to determine the pharmacokinetics profile of piperaquine in children 2 - 10 years old presenting falciparum malaria
Study objectives	Preliminary results of pharmacokinetic (PK) studies indicate that the disposition of piperaquine is altered in children compared to adults.
Ethics approval(s)	1. Institut de Recherche en Science de la Sante/Centre Muraz (IRSS/CM) (Burkina Faso) , 26/07/2007, ref: 005-2007/CE-CM 2. University of California, San Francisco (USCF) committee on Human Research, 27/07/2007, ref: # H40380-31179-01
Health condition(s) or problem(s) studied	Malaria
Intervention	Patients are given dihydroartemisin piperaquine once daily for three days. Treatment is weight based and directly observed by the study nurse. The follow up duration is 42 days. The study is a one arm study but there is a randomisation to determine the groups where the patient will be included for the PK purpose.
Intervention type	Drug
Phase	Not Applicable
Drug / device / biological / vaccine name(s)	Dihydroartemisinin-piperaquine
Primary outcome measure(s)	1. Determination of the pharmacokinetic profile of piperaquine in children with uncomplicated falciparum malaria 2. Assess the efficacy of dihydroartemisinin piperaquine
Key secondary outcome measure(s)	1. Risk of recurrent malaria* 2. Risk of clinical and parasitological treatment failure* 3. Prevalence of fever (defined as both subjective fever in the previous 24 hours and measured axillary temperature greater than 37.5ºC) on follow-up days 1, 2, and 3 4. Prevalence of parasitaemia on follow-up days 2 and 3 5. Change in mean haemoglobin from day 0 to 42 (or day of rescue therapy for patients classified as late clinical failure [LCF] or late parasitological failure [LPF]) 6. Prevalence of gametocytaemia on follow-up days 2, 3, 7, 14, 21 and 28 7. Change in the prevalence of molecular markers possibly associated with drug resistance on day 0 or the day of recurrent parasitaemia, including polymorphisms in Plasmodium falciparum chloroquine resistance transporter (Pfcrt) and Plasmodium falciparum multidrug-resistance (Pfmdr1) genes 8. In vitro sensitivity to antimalarial drugs *Risks will be estimated using the Kaplan-Meier product limit formula based on a modified intention-to-treat analysis.
Completion date	31/01/2008

Eligibility

Participant type(s)	Patient
Age group	Child
Lower age limit	6 Months
Sex	All
Target sample size at registration	330
Key inclusion criteria	On day 0, patients with symptoms suggestive of malaria and a positive screening thick blood smear will be assessed for the following selection criteria by study physicians for appropriate care: 1. Not previously enrolled in this study 2. Aged greater than 6 months 3. Weight greater than 5 kg 4. Fever (greater than 37.5ºC axillary) or history of fever in the previous 24 hours 5. Absence of any history of serious side effects to study medications 6. No evidence of a concomitant febrile illness in addition to malaria 7. Provision of informed consent and ability to participate in 42-day follow-up (patient has easy access to health unit) 8. No history of antimalarial use in the previous two weeks (except for chloroquine) 9. No danger signs or evidence of severe malaria defined as: 9.1. Unarousable coma (if after convulsion, greater than 30 minutes) 9.2. Recent febrile convulsions (within 24 hours) 9.3. Altered consciousness (confusion, delirium, psychosis, coma) 9.4. Lethargy 9.5. Unable to drink or breast feed 9.6. Vomiting everything 9.7. Unable to stand/sit due to weakness 9.8. Severe anaemia (haemoglobin [Hb] less than 5.0 gm/dL) 9.9. Respiratory distress (laboured breathing at rest) 9.10. Jaundice After going to the laboratory, the subjects will be referred to the study nurse for treatment allocation and treatment with the study medications. Patients must also meet the following criterion: 10. Absence of repeated vomiting of study medications on day 0 Patients will return to the clinic on day 1 and will be excluded from the study if the following inclusion criteria are not met: 11. Plasmodium falciparum mono-infection 12. Parasite density 2000 - 200,000/ul
Key exclusion criteria	1. Inhability to participate in 42 days follow up 2. Pregnant women 3. Severe malaria
Date of first enrolment	06/08/2007
Date of final enrolment	31/01/2008

Locations

Countries of recruitment

Burkina Faso
Thailand

Study participating centre

Shoklo Malaria Research Unit (SMRU)

Mae Sot
63110
Thailand

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	18/08/2014		Yes	No