Chemoprevention Efficacy Study Nigeria

• ClinicalTrials.gov Identifier: NCT05979896
• Recruitment Status: Recruiting
• First Posted: August 7, 2023
• Last Update Posted: August 7, 2023
• Sponsor: Malaria Consortium
• Information provided by (Responsible Party): Malaria Consortium

Study Description

Brief Summary:

The study aims to assess the chemoprevention efficacy of Sulfadoxine-Pyrimethamine and Amodiaquine (SPAQ) used in standard age-based dosing regimens used in Seasonal Malaria Chemoprevention (SMC) and SPAQ resistance marker prevalences and assocations among children 3 - 59 months in Sokoto and Kwara States, Nigeria.

Condition or disease	Intervention/treatment	Phase
Malaria	Drug: Standard age based SPAQ administration for SMC	Phase 4

Detailed Description:

The study aims (1) to determine the chemoprevention efficacy of Sulfadoxine-Pyrimethamine and Amodiaquine (SPAQ) used in standard age-based dosing regimens for Seasonal Malaria Chemoprevention (SMC) in children 3-59 months and (2) determine the prevalences and associations of drug resistance genotypes associated with resistance to SPAQ.

1. a prospective cohort study to determine the chemoprevention efficacy of SPAQ (if SPAQ provides 28 days of protection from Plasmodium falciparum (P. falciparum) malaria infection by clearing existing and preventing new infections) and whether drug concentrations and/or resistance influence the ability to clear and prevent these P. falciparum infections.
2. a resistance markers study in symptomatic RDT positive children 3-59 months to measure sulfadoxine-pyrimethamine and amodiaquine resistance marker prevalence and association.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 800 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: Cohort
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: A Study Protocol to Assess the Chemoprevention Efficacy of Sulphadoxine-Pyrimethamine Plus Amodiaquine (SPAQ) and Resistance Marker Prevalence in Children 3-59 Months in Sokoto and Kwara States, Nigeria.
• Actual Study Start Date: July 28, 2023
• Estimated Primary Completion Date: September 15, 2023
• Estimated Study Completion Date: May 15, 2024

Arms and Interventions

Arm

Intervention/treatment

Experimental: Sulfadoxine-Pyrimethamine + Amodiaquine (SPAQ); Children aged 3-59 months will receive directly observed therapy of standard aged based dosing of Sulfadoxine-Pyrimethamine + Amodiaquine (SPAQ) over 3 days.

Drug: Standard age based SPAQ administration for SMC; Sulfadoxine-pyrimethamine and amodiaquine (SPAQ) is administered in standard WHO approved age based regimens as used in Seasonal Malaria Chemoprevention Programmes. 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. 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. AQ 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.

Outcome Measures

Primary Outcome Measures :

1. Chemoprevention failure as defined by qPCR positive parasites or malaria slide positive parasites [ Time Frame: 28 days ]
   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).
2. Prevalence of antimalarial resistance markers among chemoprevention failures (as defined in outcome 1) [ Time Frame: 28 days ]
   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.
3. Drug concentrations of Sulfadoxine-pyrimethamine and amodiaquine among chemoprevention failures (as defined in outcome 1) [ Time Frame: 28 days ]
   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.
4. 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 [ Time Frame: 28 days preceding implementation of chemoprevention efficacy study component ]
   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

Eligibility Criteria

• Ages Eligible for Study: 3 Months to 59 Months (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion criteria

• Children between 3-59 months.
• Being resident in the research study area.
• Afebrile children 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 days DOT of standard SPAQ regimen.
• Willingness and ability of the child's 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 SPAQ.
• 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
• HIV positive or ARV use (SPAQ MUST NEVER be used with children taking the antiretroviral efavirenz)
• Chronic illness of any kind.
• Treatment with an ACT in previous 2 weeks.
• Previous treatment with SPAQ this malaria season.

Contacts and Locations

Contacts

Contact: Craig Bonnington; +447597549279; C.BONNINGTON@MALARIACONSORTIUM.ORG

Locations

Nigeria

Kwara Sentinell Site; Recruiting

Kwara, Nigeria

Contact: Mohammed Abdulkadir

Contact +2348065754333 docmohng@gmail.com

Principal Investigator: Mohammed Abdulkadir, Dr

Sponsors and Collaborators

Malaria Consortium

Investigators

• Principal Investigator: Craig Bonnington; Malaria Consortium

More Information

• Responsible Party: Malaria Consortium
• ClinicalTrials.gov Identifier: NCT05979896
• Other Study ID Numbers: SMCNGPHASE1
• First Posted: August 7, 2023
• Last Update Posted: August 7, 2023
• Last Verified: July 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Malaria Consortium:

Seasonal Malaria Chemoprevention; Chemoprevention efficacy; Antimalarial drug resistance

Additional relevant MeSH terms:

Malaria; Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases