Pan African Clinical Trials Registry
South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR201508001191898 Date of Approval: 07/07/2015
Trial Status: Retrospective registration - This trial was registered after enrolment of the first participant
TRIAL DESCRIPTION
Public title Validation of New Biomarkers for Monitoring P. falciparum Reduced susceptibility/Tolerance or Resistance to Artemisinin Derivatives and Partner Drugs
Official scientific title Validation of New Biomarkers for Monitoring Plasmodium falciparum Reduced susceptibility/Tolerance or Resistance to Artemisinin Derivatives and Partner Drugs in Nigeria.
Brief summary describing the background and objectives of the trial The rapid development and spread of chloroquine and sulfadoxine-pyrimethamine resistant Plasmodium falciparum especially in Africa, has resulted to the adoption of artemisinin-based combination therapies (ACTs) for the management of malaria infections in many countries. However, if resistance to artemisinin derivatives (ARTs) and partner drugs develops and spreads, it may be the most devastating event in the history of malaria control. Currently, reliable surveillance biomarkers of declining ARTs performance are lacking, and declines in clinical drug efficacy will be the last sign of increasing parasites resistance to these new antimalarials. Moreover, once widespread resistance is recognized it usually takes several years to change malaria treatment policy and treatment practice. As a result, drugs have often been used long after their efficacy has been seriously compromised, at great cost to life and public health. The major goal of the proposed research is to use a unique, innovative and integrated approach that powerfully combines, clinical studies with essential molecular parasitology and epidemiology and cutting edge genomics analysis of fresh Plasmodium falciparum sample directly from patients, in order to identify and validate new biomarkers/molecular determinants of parasites response to ARTs and partner drugs in vitro and in vivo. New biomarkers/molecular determinants of parasites reduced susceptibility/tolerance or resistance to ARTs and partner drugs identified under this project will be collated with SNPs/ SNPs patterns or haplotypes in transporter genes with clinical responses parameters (parasites reduction ratio, parasites and fever clearance times, and blood drug levels), patients of treatment outcomes and in vitro quantitative responses.
Type of trial RCT
Acronym (If the trial has an acronym then please provide)
Disease(s) or condition(s) being studied Infections and Infestations
Sub-Disease(s) or condition(s) being studied Malaria
Purpose of the trial Treatment: Other
Anticipated trial start date 09/01/2009
Actual trial start date 09/01/2009
Anticipated date of last follow up 28/02/2012
Actual Last follow-up date 28/02/2012
Anticipated target sample size (number of participants) 0
Actual target sample size (number of participants) 371
Recruitment status Completed
Publication URL
Secondary Ids Issuing authority/Trial register
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Parallel: different groups receive different interventions at same time during study Randomised Simple randomization using a randomisation table created by a computer software program Sealed opaque envelopes Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group artemether plus lumefantrine 5 ¿ 14 kg (20/120mg of artemether/lumefantrine) and 15 ¿ 24 kg (40/240mg of artemether/lumefantrine) twice daily 3 days 104
Experimental Group artesunate plus amodiaquine 4mg/body weight of artesunate plus10mg/body weight of amodiaquine(once daily) 3 days 267
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
Symptoms compatible with acute uncomplicated malaria with pure Plasmodium falciparum parasitemia. Microscopically confirmed P. falciparum infection with parasite density ¿ 2,000/¿l of blood Body (axillary) temperature > 37.4oC or history of fever 24 ¿ 48 hours preceding presentation. No have other concomitant illness. No history of antimalarial use in the two weeks preceding presentation. Ability and willingness to comply with the protocol for the duration of the study and to comply with the study visit schedule. Written informed consent given by parents or guardians. Severe malaria Severe malnutrition. Serious underlying disease (renal, cardiac, hepatic) Concomitant febrile illness. Known allergy to study drug or its components. 6 Month(s) 15 Year(s) Both
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 24/04/2009 University of Ibadan Institutional Review Committee
Ethics Committee Address
Street address City Postal code Country
University of Ibadan Ibadan 23402 Nigeria
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Clinical outcome (cured or treatment failures) Day 0 Day 7 Day 14 Day 21 Day 28 Day 35 Day 42
Secondary Outcome Parasites reduction ratio Day 0 Day 2
Secondary Outcome Parasites and fever clearance times Day 0 Day Day Day 0 Day 1 Day 2 Day 3 Day 4 Day 5 Day 6 Day 7 Day 14 Day 21 Day 28 Day 35 Day 42
Secondary Outcome Blood drugs levels Day 0 Day 1 Day 2 Day 3 Day 4 Day 5 Day 6 Day 7 Day 14 Day 21 Day 28 Day 35 Day 42
Secondary Outcome in vitro susceptibility profiles of parasites from patient isolates Day 0 Day 7 Day 14 Day 21 Day 28 Day 35 Day 42
Secondary Outcome Mutations/haplotypes in transporter Plasmodium falciparum transporter genes Day 0 Day 1 Day 2 Day 3 Day 4 Day 5 Day 6 Day 7 - 13 Day 14 - 20 Day 21 - 27 Day 28 - 34 Day 35 - 41 Day 42
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Malaria Research Clinic and Laboratories Inst. of Medical Research and Training, College of Medicine Ibadan Nigeria
FUNDING SOURCES
Name of source Street address City Postal code Country
EDCTP The Hague, Netherlands
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor EDCTP The Hague, Netherlands Funding Agency
COLLABORATORS
Name Street address City Postal code Country
Malaria Research Clinic and Laboratories Inst. of Medical Research and Training, College of Medicine Ibadan Nigeria
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Christian Happi christianhappi@hotmail.com 08023383684 Malaria Research Laboratories, IMRAT, College of Medicine, University of Ibadan
City Postal code Country Position/Affiliation
Ibadan 23402 Nigeria
Role Name Email Phone Street address
Public Enquiries Grace Olusola Gbotosho solagbotosho@yahoo.co.uk 08030757071 Dept. of Pharmacology & Therapuetics, University of Ibadan
City Postal code Country Position/Affiliation
Ibadan Nigeria Professor
Role Name Email Phone Street address
Scientific Enquiries Christian Happi christianhappi@hotmail.com 08023383684 Malaria Research Laboratories, IMRAT, College of Medicine, University of Ibadan
City Postal code Country Position/Affiliation
Ibadan 23402 Nigeria Professor
REPORTING
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