A randomised, open label, controlled trial to assess the efficacy and safety of dihydroartemisinin-piperaquine for the treatment of primary and the prevention of secondary infections with Plasmodium falciparum

ISRCTN	ISRCTN88705995
DOI	https://doi.org/10.1186/ISRCTN88705995
Protocol serial number	1.0.6
Sponsor	University of Heidelberg School of Medicine (Germany)
Funders	Medicines for Malaria Venture (MMV) (Switzerland), German Research Council (Deutsche Forschungsgemeinschaft [DFG]) (Germany)

Submission date: 09/06/2008
Registration date: 24/07/2008
Last edited: 10/05/2012

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

Dr Steffen Borrmann
Scientific

Im Neuenheimer Feld 350
Heidelberg
69120
Germany

Phone	+49 (0)6221 56 7756
Email	steffen.borrmann@urz.uni-heidelberg.de

Study information

Primary study design	Interventional
Study design	Randomised, open label, controlled trial
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
Scientific title	A randomised open label study to assess the safety and efficacy of dihydroartemisinin-piperaquine (Artekin™) compared with lumefantrine-artemether (Coartem®) for the treatment of uncomplicated Plasmodium falciparum malaria in Kenyan children
Study objectives	Dihydroartemisinin-piperaquine is at least as efficacious as artemether-lumefantrine for the treatment of primary and the prevention of secondary infections with Plasmodium falciparum.
Ethics approval(s)	Ethics approval received from: 1. Kenya Medical Research Institute, National Ethic Review Committee (Kenya) on the 26th June 2005 2. University of Oxford, Oxford Tropical Research Ethics Committee (UK) on the 6th July 2005 3. University of Heidelberg School of Medicine, Ethics Committee (Germany) on the 8th August 2005
Health condition(s) or problem(s) studied	Uncomplicated Plasmodium falciparum malaria
Intervention	1. Three-day, three-dose regimen of dihydroartemisinin-piperaquine (Artekin™); co-formulation: target dose of 2 mg/kg/ once per day of dihydroartemisinin and target dose of 18 mg/kg/once per day of piperaquine 2. Three-day, six-dose regimen of artemether-lumefantrine (Coartem®); co-formulation containing 20 mg of artemether and 120 mg of lumefantrine: 2.1. 5 kg to less than 15 kg: one tablet/twice per day 2.2. 15 kg to less than 25 kg: two tablets/twice per day 2.3. 25 kg to less than 35 kg: three tablets/twice per day Patients are followed-up for 84 days.
Intervention type	Drug
Phase	Not Specified
Drug / device / biological / vaccine name(s)	Dihydroartemisinin-piperaquine (Artekin™), lumefantrine-artemether (Coartem®)
Primary outcome measure(s)	1. The cure ratio of dihydroartemisinin-piperaquine is non-inferior to that of artemether-lumefantrine (non-inferiority margin = 5%) 2. The cure ratio of dihydroartemisinin-piperaquine is at least 90%
Key secondary outcome measure(s)	1. Polymerase chain reaction (PCR)-uncorrected day 28 cure ratio 2. Safety profiles of the two treatments 3. Time to asexual parasite clearance (PCT) 4. Time to fever clearance (FCT) 5. Gametocyte prevalence and density on days 7, 14, 28, 42, 63 and 84 6. Haematological recovery (Haemoglobin [Hb] changes) from day 0 to day 28, day 42, and day 84 7. Cure ratios at day 42 (PCR corrected and PCR uncorrected) 8. Cure ratios at day 63 (PCR corrected and PCR uncorrected) 9. Cure ratios at day 84 (PCR corrected and PCR uncorrected) 10. Rate of PCR-confirmed reinfections to estimate the chemoprophylactic effect of dihydroartemisinin-piperaquine
Completion date	31/12/2008

Eligibility

Participant type(s)	Patient
Age group	Child
Lower age limit	6 Months
Upper age limit	59 Months
Sex	All
Target sample size at registration	500
Key inclusion criteria	1. Males and females aged between 6 months and 59 months inclusive 2. Body weight of 5 kg and above 3. Microscopically confirmed, monoinfection of Plasmodium falciparum (parasitaemia greater than or equal to 2,000/μL to 200,000/μL) 4. History of fever in the previous 24 hours or presence of fever (axillary temperature at greater than or equal to 37.5°C) 5. Signed informed consent by the parents or guardians 6. Parents or guardians willingness and ability to comply with the study protocol for the duration of the trial
Key exclusion criteria	1. Participation in any investigational drug study during the previous 30 days 2. Known hypersensitivity to the study drugs 3. Severe malaria 4. Danger signs: not able to drink or breast-feed, vomiting (greater than twice in 24 hours), recent history of convulsions (greater than one in 24 hours), unconscious state, unable to sit or stand 5. Electrocardiogram (ECG) abnormality that requires urgent management 6. Presence of intercurrent illness or any condition which in the judgment of the investigator would place the subject at undue risk or interfere with the results of the study 7. Severe malnutrition (defined as weight for height less than 70% of the median National Center for Health Statistics [NCHS]/World Health Organisation [WHO] reference)
Date of first enrolment	01/09/2005
Date of final enrolment	31/12/2008

Locations

Countries of recruitment

Germany
Kenya

Study participating centre

Im Neuenheimer Feld 350

Heidelberg
69120
Germany

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	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	01/10/2011		Yes	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes