Chemoprevention Efficacy Study in Burkina Faso

Seasonal Malaria Chemoprevention in Burkina Faso : Chemoprevention Efficacy Study

The aim of this study is to determine whether Seasonal Malaria Chemoprevention (SMC) remains effective in the health district of Nanoro in the Centre-Ouest region or Boussé in the Plateau Central region. It also aims to assess the protective efficacy of the antimalarial drugs used in SMC in the target population and to investigate levels of parasite resistance in the study districts. According to the results, this trial should provide the evidence needed to change the drugs used in SMC.

A Type II hybrid effectiveness-implementation study design will be used to evaluate the effects of a clinical intervention on relevant outcomes whilst collecting information on implementation. It is designed to determine feasibility and effectiveness of an innovative intervention, as well as the protective efficacy of the antimalarial drugs used. The study consists of two components: 1) Conducting a prospective cohort study to determine the protective efficacy of the drug combination Sulfadoxine-Pyrimethamine and Amodiaquine (SPAQ) (if SPAQ provides 28 days of protection from infection) and whether drug concentrations and/or resistance influence the duration of protection; 2) Conducting a resistance markers study in symptomatic patients in the research district.

Study Overview

• Status: Active, not recruiting
• Conditions: Malaria
• Intervention / Treatment: Drug: Sulfadoxine pyrimethamine; Drug: Amodiaquine

Detailed Description

This cohort study aims to evaluate the effects of a clinical intervention on relevant outcomes whilst collecting information on implementation.

The study uses pragmatic implementation research with the objective of contributing to the development of practical recommendations for health policy, practice and potential scale up. It is designed as an implementation study to determine effectiveness and protective efficacy to gather evidence of the potential impact on health outcomes. Five monthly cycles of SMC will be implemented between July and October 2022 in one district, Nanoro, in Centre Ouest region.

The study will comprise the following two components:

1. A prospective protective efficacy cohort study to determine if SPAQ provides 28 days of protection from infection and whether drug concentrations and/or resistance influence the duration of protection
2. A resistance markers study in children 3-59 months in the two research districts plus the two standard intervention districts to measure changes in resistance marker prevalence over time (pre and post within the same year and between years)

• Study Type: Interventional
• Enrollment (Actual): 800
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Kevin N Baker, PhD; Phone Number: 00447811266539; Email: k.baker@malariaconsortium.org

Study Locations

• Burkina Faso
  • Nanoro, Burkina Faso, BP 18
    • Unité de Recherche Clinique de Nanoro

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 months to 4 years (Child)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Children between 3-59 months
• Being resident in the project area
• Afebrile with no other malaria associated symptoms in the past 48 hours or at time of recruitment
• Consent to participate in the study obtained
• Can comply with 3 day DOT of standard SPAQ regimen (day 0-2)
• Willingness and ability of the childs guardians to comply with the study protocol for the duration of the study including all dry blood spot and slide collections

Exclusion Criteria:

• Symptoms of malaria (tympanic fever ≥ 37.5 °C or history of fever in past 48 hours)
• Known allergy to medicine provided
• Receiving a sulfa-based medication for treatment or prophylaxis, including co-trimoxazole (trimethoprim-sulfamethoxazole).
• Individuals receiving azithromycin due to the antimalarial activity of azithromycin.
• Severe malnutrition according to WHO guidelines
• Recruited in cross sectional surveys or any other SMC studies.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Sulfadoxine-Pyrimethamine + Amodiaquine (SPAQ); Children aged 3-59 months will receive SPAQ during the study period.

Drug: Sulfadoxine pyrimethamine; Sulphadoxine is a slowly eliminated sulphonamide. It is used in a fixed dose combination of 20 parts sulphadoxine with 1 part pyrimethamine given orally or intramuscularly. The medicine is no longer recommended for the treatment of malaria. However, it is being used for Intermittent Preventive Treatment during pregnancy (IPTp) and as a co-packaged combination with amodiaquine for seasonal malaria chemoprevention. Sulphadoxine is readily absorbed from the GIT. It is widely distributed in body tissues and fluids and crosses the placenta into foetal circulation. It is also readily detectable in breast milk. It is excreted predominantly as the unchanged drug.; Other Names: SP; Drug: Amodiaquine; Amodiaquine is a Mannich base 4 amino-quinoline that interferes with parasite haem detoxification. It is more effective than chloroquine in both chloroquine sensitive and resistant P. falciparum infections. However, there is cross-resistance between chloroquine and amodiaquine. It is readily absorbed in the GIT and rapidly converted in the liver to the active metabolite, desethylamodiaquine. Desethylamodiaquine is responsible for all the antimalarial effect. Adverse effect of amodiaquine includes abdominal discomfort and vomiting weakness and when used for prophylaxis it causes agranulocytosis. Amodiaquine is recommended as a partner drug in artemisinin based combination therapy.; Other Names: AQ

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Chemoprevention failure as defined by qPCR positive parasites or malaria slide positive parasites	Malaria slides and dry blood spots (DBS) taken at days 0,7,14, 21, 28 of a one month drug administration cycle will be analysed to detect parasitemia in children treated with SPAQ. Chemoprevention failure has occured if a malaria slide is positive for parasites 7 days or more after drug administration or if a qPCR detects low level parasitemia at the end of the administration cycle (one month).	One month
Prevalence of antimalarial resistance markers among chemoprevention failures (as defined in outcome 1)	All Dried blood spots (DBS) will be analysed for malaria mutation genotypes (dhfr, dhps, Pfcrt, pfmdr1) on baseline and endline and additionally throughout the cycle if a chemoprevention failure (as defined in outcome 1) has occured.	One month
Drug concentrations of Sulfadoxine-pyrimethamine and amodiaquine among chemoprevention failures (as defined in outcome 1)	Drug concentrations of SPAQ will be analyzed on all samples (taken at days 7,14,21,28 throughout the one month cycle) in order to be linked to chemoprevention failures as defined in outcome 1.	One month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevalence over time of parasites with dhfr/dhps/pfcrt/pfmdr1 mutations in symptomatic children with a positive diagnostic test residing in districts where SMC is implemented	The outcome measure to meet the secondary objective is the prevalence of molecular markers associated with SP (codons 108, 51 and 59 in dhfr and 437, 540 and 581 in dhps) and amodiaquine (codons 72-76 Pfcrt and 86, 184 and 1246 pfmdr1), as well as other markers of parasite genetic diversity, in blood samples collected from symptomatic children under five years with a positive RDT attending selected health facilities in areas with SMC.	Five months

Collaborators and Investigators

• Sponsor: Malaria Consortium
• Investigators: Principal Investigator: Gauthier Tougri, NMCP Manager

Study record dates

Study Major Dates

• Study Start (Actual): July 15, 2022
• Primary Completion (Actual): October 1, 2022
• Study Completion (Estimated): December 1, 2023

Study Registration Dates

• First Submitted: July 15, 2022
• First Submitted That Met QC Criteria: July 26, 2022
• First Posted (Actual): July 28, 2022

Study Record Updates

• Last Update Posted (Actual): November 1, 2023
• Last Update Submitted That Met QC Criteria: October 31, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Seasonal-Malaria-Chemoprevention
• Additional Relevant MeSH Terms: Infections; Vector Borne Diseases; Parasitic Diseases; Protozoan Infections; Malaria; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Folic Acid Antagonists; Anti-Infective Agents, Urinary; Pyrimethamine; Sulfadoxine; Fanasil, pyrimethamine drug combination; Amodiaquine
• Other Study ID Numbers: SMCBFPHASE1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No