Open-label randomised clinical trial of pharmacokinetics, efficacy, and tolerability of the fixed-dose artesunate/amodiaquine combination therapy versus both drugs administered separately for treatment of uncomplicated falciparum malaria in Kenya

ISRCTN ISRCTN16409445
DOI https://doi.org/10.1186/ISRCTN16409445
Secondary identifying numbers 1199
Submission date
05/07/2007
Registration date
21/08/2007
Last edited
28/03/2017
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 Bernhards Ogutu
Scientific

Walter Reed Project
Centre for Clinical Research
KEMRI
PO Box 54
Kisumu
-
Kenya

Study information

Study designOpen-label randomised single-centre clinical trial
Primary study designInterventional
Secondary study designRandomised controlled trial
Study setting(s)Not specified
Study typeTreatment
Participant information sheet Not available in web format, please use the contact details to request a patient information sheet
Scientific titleOpen-label randomised clinical trial of pharmacokinetics, efficacy, and tolerability of the fixed-dose artesunate/amodiaquine combination therapy versus both drugs administered separately for treatment of uncomplicated falciparum malaria in Kenya
Study objectives1. To investigate pharmacokinetic parameters of the fixed-dose artesunate/amodiaquine (AS/AQ) combination in adults with comparison to separate administration of the two drugs using a population pharmacokinetic design
2. To measure the clinical and parasitological efficacy of the fixed-dose AS/AQ combination therapy
3. To measure the parasite reduction ratio at 48 hours of treatment, parasite and fever clearance rates, proportions of patients with gametocyte persistence during follow up
4. To evaluate the incidence of adverse events
5. To formulate recommendations and to enable the Kenyan Ministry of Health to make informed decisions about the possible need for updating of the current national antimalarial treatment guidelines
Ethics approval(s)Ethics committee of the Kenya Medical Research Institute, 22/05/2007
Health condition(s) or problem(s) studiedUncomplicated falciparum malaria
InterventionPatients will be equally randomised into the following treatment groups:
Group A: fixed-dose AS/AQ combination tablets (100 mg/270 mg), two tablets once daily for three consecutive days.
Group B: AS tablets (50 mg): four tablets once a day for three consecutive days, and AQ tablets (153 mg): four tablets once a day for three consecutive days.

Patients will be followed-up for 28 days, and the total follow-up for the study will be 9 months.
Intervention typeDrug
Pharmaceutical study type(s)
PhaseNot Applicable
Drug / device / biological / vaccine name(s)Artesunate, amodiaquine
Primary outcome measureThe primary objective of this study is to investigate the pharmacokinetic properties of fixed-dose combination AS/AQ. Blood sampling will be performed at predefined time points in both groups of patients. The evaluation of pharmacokinetics variables will take place over the three-day treatment and the entire follow-up off-treatment.
Secondary outcome measures1. Treatment outcomes: the classification of treatment outcomes will be based on an assessment of the parasitological and clinical outcome of antimalarial treatment according to the latest (2005) guidelines of World Health Organisation (WHO). Accordingly, all patients will be classified as having an Early Treatment Failure, a Late Clinical Failure, a Late Parasitological Failure, or an Adequate Clinical and Parasitological Response
2. Safety variables: the occurrence of any adverse event will be documented. All patients will be routinely asked about old symptoms and new symptoms emerging since previous visit during follow-up
Overall study start date09/07/2007
Completion date30/03/2008

Eligibility

Participant type(s)Patient
Age groupAdult
Lower age limit18 Years
SexBoth
Target number of participants50
Key inclusion criteria1. Adults from 18 to 60 years of age; either gender
2. Presenting with acute uncomplicated falciparum malaria:
2.1. Oral temperature greater than 37.5°C, or
2.2. History of fever in the last 24 hours
3. Positive P. falciparum parasitaemia (greater than 1000 asexual parasites/µL)
4. Written informed consent
Key exclusion criteria1. Any other concomitant febrile illness, e.g. upper respiratory tract infection or Ear, Nose and Throat (ENT) infection
2. Features of severe malaria
3. Mixed Plasmodium infection
Date of first enrolment09/07/2007
Date of final enrolment30/03/2008

Locations

Countries of recruitment

  • Kenya

Study participating centre

Walter Reed Project
Kisumu
-
Kenya

Sponsor information

Drugs for Neglected Diseases initiative (DNDi) (Switzerland)
Research organisation

15 Chemin Louis Dunant
Geneva
CH-1202
Switzerland

http://www.dndi.org/
ROR logo https://ror.org/022mz6y25

Funders

Funder type

Research organisation

Drugs for Neglected Diseases initiative (DNDi) (Switzerland)

No information available

Ministerie van Buitenlandse Zaken
Government organisation / National government
Alternative name(s)
Dutch Ministry of Foreign Affairs, Ministry of Foreign Affairs, Ministry of Foreign Affairs of the Kingdom of the Netherlands
Location
Netherlands
Medecins Sans Frontieres (MSF) (International)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot provided at time of registration
Publication and dissemination planNot provided at time of registration
IPD sharing plan

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Results article results 01/06/2010 Yes No

Editorial Notes

28/03/2017: Publication reference added.

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