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.: PACTR202301796134887 Date of Approval: 19/01/2023
Trial Status: Retrospective registration - This trial was registered after enrolment of the first participant
TRIAL DESCRIPTION
Public title TES study
Official scientific title EFFICACY AND SAFETY OF ARTEMETHER LUMEFANTRINE, PYRONARIDINE ARTESUNATE, 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 Early, effective treatment is the cornerstone of malaria control. In line with this, Uganda adopted artemisinin-based combination therapy (ACT) for the treatment of uncomplicated malaria. In Uganda the first line treatment for uncomplicated malaria is artemether-lumefantrine (AL), the first line alternative is artesunate-amodiaquine (ASAQ), and the second line is dihydroartemisinin-piperaquine (DP). Of recent pyronaridine-artesunate has been approved for the treatment of uncomplicated malaria by the Uganda national drug authority. 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 parasites. They 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 the analysis of trends. According to WHO policy, a change in an antimalarial medicine recommended in the national malaria treatment policy should be initiated if the percentage of genotype-corrected treatment failure is ≥ 10%, as assessed by TES. Routine monitoring of the efficacy of antimalarial drugs is necessary for effective case management and early detection of resistance. It is important for the country to continuously assess the efficacy and safety of its first- and second-line regimens to detect early development of resistance to these drugs. In line with the above, we are conducting this study to assess the efficacy and safety of artemether-lumefantrine, pyronaridine-artesunate artesunate-amodiaquine, and dihydroartemisinin-piperaquine for the treatment of uncomplicated P. falciparum malaria.
Type of trial RCT
Acronym (If the trial has an acronym then please provide) TES
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 01/11/2022
Actual trial start date 17/11/2022
Anticipated date of last follow up 30/04/2023
Actual Last follow-up date
Anticipated target sample size (number of participants) 1350
Actual target sample size (number of participants)
Recruitment status Recruiting
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
Factorial: participants randomly allocated to either no, one, some or all interventions simultaneously 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 AL treatment arm six doses are given at 0, 8, 24, 36, 48, 60 hours based on weight 3 days Children aged 6 months to 10 years will be given all the six doses with milk as directly observed treatment and then followed up for 28 days 850
Experimental Group DP Three doses given based on weight for three days 3 Children aged 6 months to 10 years will be given the drug as directly observed treatment and followed up for 42 days 200
Experimental Group PA three doses given for three days 3 Children aged 6 months to 10 years will be given the drug as a directly observed treatment and followed up for 42 days 200
Experimental Group ASAQ three doses over a period of three days 3 Children aged 6 months to 10 years will be given the drug as directly observed treatment and follow up for 28 days 100
Control Group none no control 0 0 0 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; • Haemoglobin > 8.0 g/dl • presence of general danger signs in children aged under 11 years or signs of severe falciparum malaria according to the definitions of WHO (Appendix 1); • 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: 13 Month(s)-24 Month(s),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 12/04/2021 Makerere University School of Biomedical research and ethics committe
Ethics Committee Address
Street address City Postal code Country
Kampala P.O Box 7072 Kampala 7072 Uganda
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 12/04/2022 Makerere University School of Biomedical Sciences research and ethics committee
Ethics Committee Address
Street address City Postal code Country
Kampala Mulago 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 will be distinguished from re-infection by using molecular techniques. 42 days
Secondary Outcome Parasite clearance time, the frequency and nature of adverse events; prevalence of molecular markers of drug resistance, Day7 blood concentration of Lumefantrine. 42
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Arua regional referral hospital Arua city Arua Uganda
Masafu general hospital Busia district Busia Uganda
Patonogo HC III Agago district Agago Uganda
Moroto regional referral hospital Moroto district Moroto Uganda
Kihihi HC IV Kanungu district Kanungu Uganda
FUNDING SOURCES
Name of source Street address City Postal code Country
Presidential malaria initiative Uganda Kampala Kampala Uganda
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Secondary Sponsor PMI and Ministry of health Uganda Kampala Kampala Uganda Funding Agency
COLLABORATORS
Name Street address City Postal code Country
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Adoke Yeka yadoke@yahoo.com +256772473533 Plot 2c Nakasero
City Postal code Country Position/Affiliation
Kampala Uganda Infectious disease research institute
Role Name Email Phone Street address
Scientific Enquiries Chris Ebong echochris2@gmail.com +256782271318 Plot 2c Nakasero
City Postal code Country Position/Affiliation
Kampala Uganda Infectious disease research collaboration
Role Name Email Phone Street address
Public Enquiries Moses Kamya mkamya@idrc-uganda.org +256776520469 Plot 2c Nakasero
City Postal code Country Position/Affiliation
Kampala Uganda Infectious diseases research collaboration
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes All of the individual participant data collected during the trial will be made available on request after deidentification Study Protocol 9 months after the competition of the study data will be available by request
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