Understanding and Maximizing the Community Impact of Antimalarial Treatment (INDIE-SMC)

NCT ID: NCT05878366

Last Updated: 2025-07-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 2978 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-07-13
• Study Completion Date: 2024-03-30

Brief Summary

Seasonal Malaria Chemoprophylaxis (SMC) is a fundamental component of malaria control. The SMC program involves that sulfadoxine-pyrimethamine plus amodiaquine (SPAQ) is given to children below the age of 5 years during the peak transmission season in areas of seasonal malaria transmission. Yet, its efficacy is increasingly below expectations.

This study involves an Operational evaluation of a modified existing intervention and its implementation are prepared in direct interaction with the Ministry of Health (MoH) to tailor data collection to local needs. The main questions it aims to answer are:

1. what are the reasons for the continued high infection rates in the SMC-targeted population;

2. what are the implications for transmission of sub-optimal SMC in children less than 5 years old;

3. can the impact of SMC be improved by including older age groups that would both expand the population that experiences direct chemoprophylactic benefits and concurrently reduce transmission to the wider community

Researchers will:

i) Compare SMC effectiveness as implemented by the national malaria control program and SMC implemented in a research context where all doses are directly observed.

ii) Quantify the infectious reservoir and the contribution of different age groups to transmission with conventional SMC (<5 years) and extended SMC (<10 years) iii) Determine the impact of drug resistance and drug absorption on SMC efficacy iv) Understand social barriers and enablers interfering with SMC efficacy and how SMC uptake is related to health equity with special attention to gender inequalities.

v) Quantify SMC efficacy decay under programmatic conditions and key drivers of this decay.

Detailed Description

Seasonal Malaria Chemoprophylaxis is a well established method of malaria control. Sulfadoxine-pyrimethamine plus amodiaquine (SPAQ) is given to children below the age of 5 years during the peak transmission season in areas of seasonal malaria transmission. Whilst highly effective in controlled research studies, the impact of SMC in terms of reducing infection prevalence is less following operational delivery. It is currently unclear why and what drivers of SMC coverage and uptake play a role. In addition, the relative importance of parasite drug resistance, limited adherence, poor drug absorption and frequent re-infections remain largely unexplored.

Lastly, the World Health Organization has recently widened the scope for SMC to target all vulnerable populations. The Ministry of Health (MoH) in Burkina Faso is considering extending SMC to all children below 10 years of age; the impact of SMC on clinical incidence and parasite prevalence in this population with markedly different immunity is unknown. Moreover, this older age group is known to be highly relevant for onward malaria transmission, making it important to quantify the impact of SMC on the human infectious reservoir for malaria and broader benefits to the community.

The investigators propose a cluster-randomized trial in Saponé Health District, Burkina Faso, with three study arms:

i. SMC in children under the age of 5 years, implemented by the MoH without directly observed treatment for the full course of SMC ii. SMC in children under the age of 5 years, with directly observed treatment for the full course of SMC iii. SMC in children under the age of 10 years, with directly observed treatment for the full course of SMC The investigators will deliver the different arms of the intervention to 40 clusters of 3 households/compounds (i.e. 120 compounds per arm). The primary endpoint is parasite prevalence at the end of the malaria transmission season, secondary endpoints include the impact of SMC on clinical incidence, gametocyte carriage and potential for onward parasite transmission to mosquitoes. As relevant factors in determining these efficacies, drivers of SMC uptake and treatment adherence will be determined, as well as drug concentrations, parasite resistance markers and transmission of parasites to mosquitoes.

Conditions

Malaria; Malaria,Falciparum

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Arm 1

SMC in children under the age of 5 years, implemented by the MoH without directly observed treatment for the full course of SMC

Group Type: ACTIVE_COMPARATOR

Seasonal Malaria Chemoprophylaxis (under 5 year old) implemented by the MoH without DOT

Intervention Type: OTHER

Standard approach for SMC strategy used by the Ministry of Health (without directly-observed therapy) and without any interference of the study team. Implemented over 4 rounds, carried out in June-October 2023 with \~30 days between rounds.

Arm 2

SMC in children under the age of 5 years, with directly observed treatment for the full course of SMC

Group Type: EXPERIMENTAL

Seasonal Malaria Chemoprophylaxis (under 5 years old) with DOT

Intervention Type: OTHER

SMC will be implemented with the same number of rounds and the same timing as in active comparator arm but village health workers will visit the participants at home to administer each dose of study treatment (with DOT-directly-observed therapy)

Arm 3

SMC in children under the age of 10 years, with directly observed treatment for the full course of SMC

Group Type: EXPERIMENTAL

Seasonal Malaria Chemoprophylaxis (under 10 years old) with DOT

Intervention Type: OTHER

SMC will be implemented as in arm 2 but age of participants is extended up to 10 years: each dose of study treatment (with DOT-directly-observed therapy) distributed at home by village health workers.

Interventions

Seasonal Malaria Chemoprophylaxis (under 5 year old) implemented by the MoH without DOT

Standard approach for SMC strategy used by the Ministry of Health (without directly-observed therapy) and without any interference of the study team. Implemented over 4 rounds, carried out in June-October 2023 with \~30 days between rounds.

Intervention Type: OTHER

Seasonal Malaria Chemoprophylaxis (under 5 years old) with DOT

SMC will be implemented with the same number of rounds and the same timing as in active comparator arm but village health workers will visit the participants at home to administer each dose of study treatment (with DOT-directly-observed therapy)

Intervention Type: OTHER

Seasonal Malaria Chemoprophylaxis (under 10 years old) with DOT

SMC will be implemented as in arm 2 but age of participants is extended up to 10 years: each dose of study treatment (with DOT-directly-observed therapy) distributed at home by village health workers.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Eligible for chemoprevention for SMC as per the current recommendations
• Age 3- 59 months for arms i. and ii.
• Age 60 months up to 10 years old for arm iii.
• Absence of symptomatic falciparum malaria, defined by fever on enrolment
• Absence of other non-P. falciparum species on blood film
• No evidence of acute severe or chronic disease
• Able and willing to comply with the study protocol and follow-up schedule
• Parent or guardian provides written, informed consent on behalf of child

Exclusion Criteria

• Symptoms of malaria (axillary fever ≥ 37.5 °C and/or history of fever in the past 48 hours)
• Previous reaction to study drugs / known allergy to study drugs
• Signs of severe malaria, including hyperparasitemia (defined as asexual parasitemia > 100,000 parasites / µL)
• Signs of acute or chronic illness, including hepatitis
• The use of other medication (except for paracetamol and/or aspirin)
• Presence of severe malnutrition according to WHO's child growth standards

• Minimum Eligible Age: 3 Months
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Groupe de Recherche Action en Sante

OTHER

Sponsor Role: collaborator

Radboud University Medical Center

OTHER

Sponsor Role: collaborator

London School of Hygiene and Tropical Medicine

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Alfred Tiono, PhD, MD

Role: PRINCIPAL_INVESTIGATOR

Groupe de Recherche Action en Sante

Locations

Groupe de Recherche Action en Santé

Ouagadougou, , Burkina Faso

Countries

Burkina Faso

References

Moreno M, Barry A, Gmeiner M, Yaro JB, Serme SS, Byrne I, Ramjith J, Ouedraogo A, Soulama I, Grignard L, Soremekun S, Koele S, Ter Heine R, Ouedraogo AZ, Sawadogo J, Sanogo E, Ouedraogo IN, Hien D, Sirima SB, Bradley J, Bousema T, Drakeley C, Tiono AB. Understanding and maximising the community impact of seasonal malaria chemoprevention in Burkina Faso (INDIE-SMC): study protocol for a cluster randomised evaluation trial. BMJ Open. 2024 Mar 12;14(3):e081682. doi: 10.1136/bmjopen-2023-081682.

Reference Type: DERIVED

PMID: 38479748 (View on PubMed)

Provided Documents

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

INV-053846

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

29193

Identifier Type: -

Identifier Source: org_study_id