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.: PACTR202404710340979 Date of Approval: 30/04/2024
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title Evaluation of the efficacy of Artemisinin Combination therapy in Kenya
Official scientific title Surveillance of the invasive Anopheles stephensi malaria vector and pfcoronin and pfk13 gene variants as markers for resistance by P. falciparum to ACTs treatment in ‘resistance high risk’ border counties of Mombasa, Kwale, and Busia; A strategic
Brief summary describing the background and objectives of the trial Malaria remains a disease of public health concern with over 247 million cases and 619,000 deaths reported globally in 2021 with Kenya reporting more than 3.5 million clinical cases and over 10,000 deaths. According to the WHO, there has been a steady increase in the number of malaria cases in Kenya and sub-Saharan Africa (SSA) mostly attributed to rising resistance to the antimalarial drug regimen. This increase has also been attributed to the emergence of an invasive mosquito species Anopheles stephensi which has been linked to the increase in malaria cases in Djibouti city and an outbreak in Ethiopia. Antimalarial drug resistance markers especially on the Plasmodium falciparum Kelch propeller domain (Pfk13) have widely been reported in Southeast Asia (SEA) and have slowly found their way in SSA with cases of delayed parasite clearance being reported in Uganda and Tanzania. Treatment failure of some cases reported in West Africa has been linked to mutations in the propeller domain of Pfcoronin which could explain the reason why mutations in Pfk13 have sporadically been reported in AfricaThis study therefore seeks to conduct a therapeutic efficacy trial in the border counties of Kwale and Busia, which will be a single-arm 42-day follow-up trial on patients with uncomplicated malaria. Molecular analysis will be conducted through amplification of Pfk13 and Pfcoronin, markers associated with malaria drug resistance. Targeted sequencing will be conducted to identify any mutations in the two genes of interest. Mosquito surveillance will also be conducted in the coastal town of Mombasa and its hinterland to determine the presence of An. stephensi and whether their introduction to Kenya is through maritime trade. The major outcomes of this study will be to inform the malaria treatment guidelines in Kenya, provide baseline data for use of Pfcoronin as a marker for resistance studies and provide insight to the Ministry of Health on the status.
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 01/05/2024
Actual trial start date
Anticipated date of last follow up 30/07/2024
Actual Last follow-up date
Anticipated target sample size (number of participants) 330
Actual target sample size (number of participants)
Recruitment status Active, not 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
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 Masking/blinding used Care giver/Provider
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Control Group Artemether Lumefantrine The dosage for each participant will be determined by their weight. Each participant will get a Direct Observed Treatment (DOT) for a period of 3 days from the first day of recruitment D0, to the third day of participant follow-up, D2. 3 days Drug used for the treatment of uncomplicated malaria 165 Active-Treatment of Control Group
Experimental Group Dihydroartemisinin piperaquine The dosage for each participant will be determined by their weight. Each participant will get a Direct Observed Treatment (DOT) for a period of 3 days from the first day of recruitment D0, to the third day of participant follow-up, D2 3 days Drug used for the treatment of uncomplicated malaria 165
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
• age between 6 Months to 14 years • mono infection with P. falciparum confirmed by positive blood smear (i.e., no mixed infection). • parasitaemia of parasitaemia between 1,000 – 200,000 p/μl • presence of axillary or tympanic temperature ≥ 37.5 °C or fever history 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 a parent or guardian and an informed assent from any minor participant aged from 12 to 14 years • presence of general danger signs in children aged under 12 years or signs of severe falciparum malaria according to the definitions of WHO (Appendix 1) • weight under 5 kg. • haemoglobin < 5 g/dl • mixed or mono infection with another Plasmodium species detected by microscopy. • presence of severe malnutrition defined as a child aged between 6-60 months whose weight-for-high is below –3 z-score, • 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. • history of hypersensitivity reactions or contraindications to any of the medicine(s) being tested or used as alternative treatment(s) • a positive pregnancy test or breastfeeding; and • unable to or unwilling to take pregnancy test or to use contraception for girls of child-bearing age (defined as age > 12 years and sexually active) Child: 6 Year-12 Year,Preschool Child: 2 Year-5 Year 6 Month(s) 14 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 09/11/2023 KEMRI Scientific and Ethics Review Unit
Ethics Committee Address
Street address City Postal code Country
58540 Nairobi 00200 Kenya
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Adequate clinical Parasitological Response End of Participant follow-up
Secondary Outcome 1. Highlight the prevalence of Pfk13 antimalarial drug resistance marker. 2. Determine the use of the novel marker, Pfcoronin, as an indication for antimalarial drug resistance After recruitment of participants in all the sites and after molecular and Sequencing analysis
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Msambweni Sub county Hopsital P.O Box 8 Kwale 80405 Kenya
Matayos Sub county Hospital P.O Box 87 Busia 50524 Kenya
FUNDING SOURCES
Name of source Street address City Postal code Country
KEMRI Internal Research Grant 58540 Nairobi 00200 Kenya
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Kenya Medical Research Institute P.O Box 54840 Nairobi 00200 Kenya Government Agency
COLLABORATORS
Name Street address City Postal code Country
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Kelvin Thiongo kthiongo@kemri.go.ke +254710355565 58540
City Postal code Country Position/Affiliation
Nairobi 00200 Kenya Research Scientist Kenya Medical Research Institute
Role Name Email Phone Street address
Public Enquiries Elijah Songok director@kemri.go.ke +2540202722541 54840
City Postal code Country Position/Affiliation
Nairobi 00200 Kenya Director General Kenya Medical Research Institute
Role Name Email Phone Street address
Scientific Enquiries Enock Kebenei ekebenei@kemri.go.ke +2540717719477 54840
City Postal code Country Position/Affiliation
Nairobi 00200 Kenya Head KEMRI Scientific and Ethical Review Unit
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes Individual Participant Data will be provided after de-identification of participant data. The data will be provided 12 months after study completion and publication in peer reviewed journals. A link to the KEMRI website database on trials will be provided for access to scientists indefinitely. Analytic Code,Clinical Study Report,Informed Consent Form,Statistical Analysis Plan,Study Protocol 12 months after completion of the study and publication of data A link will be provided for access
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