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.: PACTR202401827533382 Date of Approval: 12/01/2024
Trial Status: Retrospective registration - This trial was registered after enrolment of the first participant
TRIAL DESCRIPTION
Public title Evaluation and survey of malaria chemoprevention drug resistance in infant from Koutiala, Mali
Official scientific title Monitoring and evaluation of molecular markers drug resistance during seasonal malaria chemoprevention with sulfadoxine-pyrimethamine and amodiaquine implementation in Koutiala, Mali
Brief summary describing the background and objectives of the trial In 2012, The World Health Organization (WHO) recommended seasonal malaria chemoprevention (SMC) with sulfadoxine-pyrimethamine and amodiaquine (SP+AQ) in the Sahel countries in Africa to reduce malaria among children under 5 years. This strategy has since been scaled up in the health district of Koutiala, Mali. Our primary observations of this scale-up showed an increasing prevalence of two resistance markers, Plasmodium falciparum dihydropteroate synthase (Pfdhps) 540E and Plasmodium falciparum dihydrofolate reductase (Pfdhfr)-dhps quintuple mutant genotype, in the treated population several months after the last SMC round in 2014. These very high levels of triple, quadruple and quintuple mutants could compromise the effectiveness of SP, but there are no data linking the number of mutations to in vivo resistance against SP+AQ. The use of millions of doses of SP+AQ could potentially generate more highly resistant Plasmodium falciparum mutant parasites. One of the WHO criteria for SMC implementation is >90% efficacy of SP+AQ. In 2016, however, SMC implementation expanded nationally throughout Mali, and WHO has not established a method to monitor the effectiveness of this strategy in a mass campaign. We propose that SMC efficacy could be evaluated by determining parasite clearance, molecular markers, morbidity and mortality in the target population of the health district of Koutiala, Mali. General objective. To evaluate the in vivo efficacy of SP+AQ in the SMC mass campaign among children under 5 years; measure the impact on SMC molecular resistance markers; and assess malaria morbidity and mortality. Specific objectives: 1) measure parasite clearance in treated volunteers; 2) monitor in vivo efficacy of SP+AQ on day 28; 3) determine the prevalence of Plasmodium falciparum mutations in chloroquine resistance transporter (Pfcrt), multidrug resistance transporter 1 (Pfmdr1), Pfdhfr, Pfdhps genes.A total of 10 sentinel sites in Koutiala (Mali) will be needed to recruit.
Type of trial Observational
Acronym (If the trial has an acronym then please provide) SMCDrugR
Disease(s) or condition(s) being studied Infections and Infestations
Sub-Disease(s) or condition(s) being studied Malaria
Purpose of the trial Prevention
Anticipated trial start date 01/01/2022
Actual trial start date 01/01/2022
Anticipated date of last follow up 30/10/2022
Actual Last follow-up date 30/12/2022
Anticipated target sample size (number of participants) 1000
Actual target sample size (number of participants) 1000
Recruitment status Completed
Publication URL in progress
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
Single Group Non-randomised Allocation was determined by the holder of the sequence who is situated off site Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group SMC 1. A single dose of SP 250/12.5mg on Day 1 and AQ 75mg once a day for 3 days.* for children 3-11 months 2. A single dose of SP 500/25mg on Day 1 and AQ 150mg once daily for 3 days. 4 mois Children aged 3 to 59 months living in areas where malaria is highly seasonal received SP+AQ treatment every month for 4 months. This treatment is administered during the period when malaria transmission is highest, which often coincides with the rainy season. 500
Control Group NonSMC 0 4 months The control group was the participants who did not receive SMC but live in the same area with children which take SMC. 500 Historical
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
i. Child who received SP or AQ in the previous month; ii. Child suffering from malaria diagnosed or under treatment at the time of implementation; iii. Child with a known allergy to SP or AQ; iv. adults never have taken SMC 1. Known allergy to SMC medicine 2. Child with severe malaria 3. Child on cotrimoxazole Adolescent: 13 Year-18 Year,Adult: 19 Year-44 Year,Child: 6 Year-12 Year,Infant: 0 Month(s)-12 Month(s),Infant: 13 Month(s)-24 Month(s),Middle Aged: 45 Year(s)-64 Year(s),Preschool Child: 2 Year-5 Year 3 Month(s) 65 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 06/04/2023 CE INSP
Ethics Committee Address
Street address City Postal code Country
Hippodrome Rue 235 porte 52 Bamako 1771 Mali
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Measuring molecular markers of SP+AQ resistance will provide evidence for the spread of drug-resistant parasites SMC implementation. End of study
Secondary Outcome In addition, measuring the incidence of malaria morbidity and mortality may correspond to a decline in SMC effectiveness over the past ten years. end of study
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Koutiala Health district Koutiala Mali
FUNDING SOURCES
Name of source Street address City Postal code Country
The African Academy of Sciences 8 Miotoni Lane, Karen, Nairobi Nairobi Kenya
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor AAS 8 Miotoni Lane, Karen, Nairobi Nairobi Kenya Funding Agency
COLLABORATORS
Name Street address City Postal code Country
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Hamma Maiga hmaiga@icermali.org +22376495006 hippodrome rue 235 porte 52
City Postal code Country Position/Affiliation
Bamako 1771 Mali Chef de Service Parasitologie
Role Name Email Phone Street address
Public Enquiries Samba Sow ssow@cvd-mali.org +22376348947 hippodrome rue 235 porte 52
City Postal code Country Position/Affiliation
Bamako 1771 Mali Directeur
Role Name Email Phone Street address
Scientific Enquiries Brahima Guindo guindo50@gmail.com +22376078639 hippodrome rue 235 porte 52
City Postal code Country Position/Affiliation
Bamako 1771 Mali Chef de Department labs
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes All members of the research team will undertake to preserve the confidentiality of all personal information obtained during the research process. Participants will be informed that participation in a research study may involve a breach of confidentiality, but that the confidentiality of all records will be maintained to the extent possible. The researchers will assure participants that the information collected will be kept secure and accessible only to authorized individuals throughout the research process. No personal or medical information about patients will be communicated. Part of the samples (confetti) will be stored in our INSP reference laboratory for future tests on molecular markers of antimalarial resistance. Informed Consent Form,Statistical Analysis Plan,Study Protocol May 30th 2024 SMC, Drug resistance, Molecular markers, Mali
URL Results Available Results Summary Result Posting Date First Journal Publication Date
Yes 25/12/2023
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result - 25/12/2023
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information