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: www.pactr.org
Trial no.: PACTR201811640750761 Date of Approval: 19/11/2018
Trial Status: Retrospective registration - This trial was registered after enrolment of the first participant
TRIAL DESCRIPTION
Public title Therapeutic Efficacy Studies (TES) of antimalarial
Official scientific title EFFICACY AND SAFETY OF ARTEMETHER-LUMEFANTRINE, ARTESUNATE – AMODIAQUINE AND DIHYDROARTEMISININ-PIPERAQUINE FOR THE TREATMENT OF UNCOMPLICATED PLASMODIUM FALCIPARUM MALARIA IN CHILDREN IN UGANDA
Brief summary describing the background and objectives of the trial Title: Efficacy and safety of artemether-lumefantrine, artesunate – amodiaquine and dihydroartemisinin – piperaquine for the treatment of uncomplicated Plasmodium falciparum malaria in Uganda. Background: Early, effective treatment is the cornerstone of malaria control. ACTs are currently the frontline treatments against P. falciparum malaria. The five ACTs recommended for the treatment of uncomplicated malaria are artemether–lumefantrine (AL), artesunate–amodiaquine (AS+AQ), artesunate–mefloquine (AS+MQ), artesunate–sulfadoxine–pyrimethamine (AS+SP) and dihydroartemisinin–piperaquine (DP). Although ACTs are working well in many parts of the world, there is serious concern regarding emerging resistance of malaria parasites to these vital treatments . A new molecular marker for artemisinin resistance, a series of mutations on the Kelch gene on chromosome 13 (K13) has been associated with resistant parasite phenotypes in SE Asia but it is not yet clear if K13 mutations are associated with resistance in Africa. Even more recently, failures of DP have been reported in SE Asia, these are associated with additional parasite polymorphisms, specifically increased plasmepsin copy number and a mutation in an exonuclease gene. These findings are very concerning, as they threaten the efficacy of DP to malaria. However, there is as yet no convincing evidence of DP resistance in Africa. With this background, the appropriate selection of first- and second-line antimalarial medicines and updating treatment strategies and policies for country programs should be based on the efficacy and safety of the medicines against the malaria parasite and should be guided by the results of therapeutic efficacy studies (TES). The efficacy of national first- and second line antimalarial treatments should be monitored at least once every 2 years, and should be conducted in the same regions of the country over time in order to allow analysis of trends . According to WHO policy, a change in an anti
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: Drugs
Anticipated trial start date 01/03/2018
Actual trial start date 03/09/2018
Anticipated date of last follow up 30/09/2019
Actual Last follow-up date
Anticipated target sample size (number of participants) 1000
Actual target sample size (number of participants)
Recruitment status Recruiting
Publication URL
Secondary Ids Issuing authority/Trial register
CTA 0067 Uganda National Drug Authority
HS 2415. Uganda National Council of Science and Technology
SBS 539 Makerere University College of Health Sciences, School of Biomedical Sciences Higher Degrees Research and Ethics Committee
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 randomization 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 Dihydroartemisinin piperaquine once daily fixed dose tablets (40 mg dihydroartemisinin + 320 mg piperaquine). Amount given is according to weight-based guidelines. 3 days Study patients are randomized to treatment with one of the three study regimens of Artemether-lumefantrine (AL), Amodiaquine + Artesunate (ASAQ) and Dihydroartemisinin-piperaquine (DP). Those randomized to the DP group receive DP once daily for 3 days given in fixed dose tablets (40 mg dihydroartemisinin + 320 mg piperaquine) according to weight-based guidelines. The treatment is given as Directly Observed Treatment. The study patients are then followed up for 42 days. 300
Experimental Group Amodiaquine Artesunate Once daily dose of AS+AQ given according to the patient’s body weight. 3 days Study patients randomised to Amodiaquine + Artesunate (ASAQ) takes once daily dose for 3 days given as fixed dose tablets. The treatment is given as Directly Observed Treatment. The study patients are then followed up for 28 days. 200
Control Group Artemether lumefantrine twice daily fixed dose tablets (20 mg artemether + 120 mg lumefantrine) given according to weight-based guidelines 3 days Study patients randomised to Artemether-lumefantrine (AL) takes twice daily dose for 3 days given as fixed dose tablets. The treatment is given as Directly Observed Treatment. The study patients are then followed up for 28 days if the experimental arm is ASAQ and 42 days if the experimental arm is DP. 500 Uncontrolled
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
• Age 6 months to 10 years; • Mono-infection with P. falciparum confirmed by positive blood smear; • Parasitaemia of 2000 to 200000 asexual forms/µl; • Presence of axillary temperature ≥ 37.5 °C or history of fever during the past 24 h; • Ability to swallow oral medication; • Ability and willingness to comply with the study protocol for the duration of the study and to comply with the study visit schedule; • Informed consent from parent or guardian; • Presence of general danger signs in children aged under 11 years or signs of severe falciparum malaria according to the definitions of WHO • Weight under 5 kg; • Mixed or mono-infection with another Plasmodium species detected by microscopy; • Presence of severe malnutrition defined as a very low weight for height (below -3z scores of the median WHO growth standards), by visible severe wasting, or by the presence of nutritional oedema. In a child aged between 6-60 months who has a mid-upper arm circumference < 115 mm; • Presence of febrile conditions due to diseases other than malaria (e.g. measles, acute lower respiratory tract infection, severe diarrhea with dehydration) or other known underlying chronic or severe diseases (e.g. cardiac, renal and hepatic diseases, HIV/AIDS); • Regular medication, which may interfere with antimalarial pharmacokinetics (Ongoing prophylaxis with drugs having antimalarial activity such as cotrimoxazole for the prevention of Pneumocystis carini pneumonia in children born to HIV positive women); • History of hypersensitivity reactions or contraindications to any of the medicine(s) being tested or used as alternative treatment(s). Child: 6 Year-12 Year,Infant: 1 Month-23 Month,Preschool Child: 2 Year-5 Year 6 Month(s) 10 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 16/01/2018 School of Biomedical Sciences Higher Degrees Research and Ethic Committee
Ethics Committee Address
Street address City Postal code Country
Mulago Hospital Kampala 7072 Uganda
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome The proportion of patients with early treatment failure, late clinical failure, late parasitological failure or an adequate clinical and parasitological response as indicators of efficacy. Recrudescence distinguished from re-infection by polymerase chain reaction (PCR) analysis. outcome detected at any point during the active follow up.
Secondary Outcome The frequency and nature of adverse events; outcome detected at any point during the follow up
Secondary Outcome Polymorphism of molecular markers for amodiaquine, piperaquine, lumefantrine and artemisinin. outcome detected at any point during the active follow up.
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Masafu general Hospital Busia District Eastern Uganda Kampala Uganda
Aduku Health Centre IV Kwania District Northern Uganda Kampala Uganda
Arua Regional Refferal Hospital Arua District West Nile Region Kampala Uganda
Kasambya Health Centre III Mubende district Central Uganda Kampala Uganda
Kihihi health centre IV Kanungu district Western Uganda Kampala Uganda
FUNDING SOURCES
Name of source Street address City Postal code Country
United States Agency for International Development 1201 Pennsylvania Ave., NW Suite 200, Washington, DC 20004, USA Washington DC United States of America
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor United States Agency for International Development 1201 Pennsylvania Ave., NW Suite 200, Washington, DC 20004, USA Washington DC United States of America Funding Agency
Primary Sponsor Uganda PMI in country team plot 1577, Ggaba Road, Kampala, Uganda Kampala Uganda Funding Agency
COLLABORATORS
Name Street address City Postal code Country
Uganda National Malaria Control Program Ministry of Health Uganda Box 7272, Kampala, Uganda Kampala Uganda
Infectious Diseases Research Collaboration Kampala Uganda Plot 2C Nakasero Hill road, Kampala, Uganda Kampala Uganda
Uganda Malaria Action Program for Districts Plot 25 Upper Naguru East Road, Kampala, Uganda Kampala Uganda
WHO Uganda Country Office Plot 60 Prince Charles Avenue, Kololo, Kampala Kampala Uganda
University of California San Francisco San Francisco General Hospital, 1001 Potrero Avenue, Building 30, Room 402/408, San Francisco, CA 94110, USA San Francisco United States of America
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Adoke Yeka yadoke@yahoo.com +256772473533 Plot 2C Nakasero Hill road, Kampala, Uganda
City Postal code Country Position/Affiliation
Kampala 7475 Uganda Researcher at Infectious Diseases Research Collaboration Kampala Uganda
Role Name Email Phone Street address
Principal Investigator Moses Kamya mkamya@idrc-uganda.org +256776520469 Plot 2C Nakasero Hill road, Kampala, Uganda
City Postal code Country Position/Affiliation
Kampala 7475 Uganda Executive Director Infectious Diseases Research Collaboration
Role Name Email Phone Street address
Scientific Enquiries Chris Ebong cebong@idrc-uganda.org +256782271318 Plot 2C Nakasero Hill road, Kampala, Uganda
City Postal code Country Position/Affiliation
Kampala 7475 Uganda Study coordinator Infectious Diseases Research Collaboration
Role Name Email Phone Street address
Public Enquiries Sam Gudoi Siduda s.gudoi@malariaconsortium.org 256772744084 Plot 25 Upper Naguru East Road, Kampala, Uganda
City Postal code Country Position/Affiliation
Kampala Uganda Chief of Party Malaria Action Program for District
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Undecided
URL Results Available Results Summary Result Posting Date First Journal Publication Date
No
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information