Effectiveness, Feasibility and Acceptability of Seasonal Malaria Chemoprevention in Aweil South County in South Sudan

NCT05471544 | Unknown Phase 3

• 1 other identifier: SMCSSPHASE1
• Study Type: interventional
• Target: 3,575
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to explore whether SMC is an effective intervention in the context of Northen Bahr el Gazal state, South Sudan. It also aims to assess the protective efficacy of the antimalarials used in SMC in the target population and investigate levels of parasite resistance in the study counties. If successful, this trial should provide the evidence for SMC to be included in malaria programming and policy in South Sudan. 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 five components: 1) A series of cross-sectional surveys establishing confirmed malaria cases in children; 2) A prospective cohort study to determine the protective efficacy of SPAQ (if SPAQ provides 28 days of protection from infection) and whether drug concentrations and/or resistance influence the duration of protection; 3) A resistance markers study in children 3-59 months in the research county; 4) Modelling the protective effect of SPAQ in South Sudan to determine where SMC could be a suitable malaria prevention strategy in other areas of the country, and 5) A process evaluation to understand feasibility and acceptability of the SMC intervention in South Sudan.

Conditions

Malaria

Keywords

seasonal-malaria-chemoprevention

Outcome Measures

Primary Outcomes (4)

• Malaria incidence in study population in intervention county and eligible children in one control county

  Number of malaria cases in the intervention population and eligible children in one control county over the study period as reported through care givers in cross-sectional surveys at baseline, mid-intervention and endline

  Five months

• Chemoprevention failure as defined by positive parasites in malaria slides after day 7 or positive qPCR in dried blood spot (DBS) on day 28

  Malaria slides and dry blood spots (DBS) taken at days 0,7, 28 will be analysed with qPCR methodology to detect low level submicroscopic parasitemia in children treated with SPAQ

  One month

• Prevalence of antimalarial resistance markers (dhfr, dhps, Pfcrt, pfmdr1) among chemoprevention failures as defined in outcome 2

  All Dried blood spots (DBS) will be analysed for malaria mutation genotypes (dhfr, dhps, Pfcrt, pfmdr1) on baseline and endline and additionally on day 7, day 28, or if participant slide is positive for parasites on day 7 or an infection is reported through care givers in cross-sectional survey.

  One month

• Drug concentrations of Sulfadoxine-pyrimethamine and amodiaquine among chemoprevention failures (as defined in outcome 1)

  Drug concentrations will be analyzed for all samples on baseline, day 7 and day 28 and will be linked to chemoprevention failure cases as defined in outcome 2 or a malaria infection is reported through care givers in cross sectional survey.

  One month

Study Arms (2)

Sulfadoxine-Pyrimethamine + Amodiaquine (SPAQ)

EXPERIMENTAL

Children aged 3-59 months will receive SPAQ in the intervention arm

Drug: Sulfadoxine pyrimethamine; Drug: Amodiaquine

Control

NO INTERVENTION

Children aged 3-59 months will not receive SPAQ in the control arm

Interventions

Sulfadoxine pyrimethamine DRUG

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.

Also known as: SP

Sulfadoxine-Pyrimethamine + Amodiaquine (SPAQ)

Amodiaquine DRUG

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.

Also known as: AQ

Sulfadoxine-Pyrimethamine + Amodiaquine (SPAQ)

Eligibility Criteria

• Age: 3 Months - 59 Months
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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.
• Children with HIV
• Previous treatment with Amodiaquine in the past 28 days (treatment with ASAQ or SPAQ)

Sponsors & Collaborators

• Malaria Consortium: lead

Study Sites (1)

Aweil South

Aweil, Northern Bahr El Gazal, South Sudan

Location

MeSH Terms

Conditions

Malaria

Interventions

fanasil, pyrimethamine drug combination; Amodiaquine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Ahmed Ismail Julla

  Ministry of Health, South Sudan

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 15, 2022
• First Posted: July 25, 2022
• Study Start: July 18, 2022
• Primary Completion: December 15, 2024
• Study Completion: December 31, 2024
• Last Updated: March 25, 2024

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

SO (1)