Clinical trial

Effectiveness, Feasibility and Acceptability of Seasonal Malaria Chemoprevention in Aweil South County in Northern Bahr Eel Ghazal, South Sudan: A Type 2 Hybrid Effectiveness-implementation Study Using a Convergent Mixed-methods Approach

Name

SMCSSPHASE1

Description

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.

Trial arms

Trial start

2022-07-18

Estimated PCD

2024-12-15

Trial end

2024-12-31

Status

Active (not recruiting)

Phase

Early phase I

Treatment

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.

Arms:

Sulfadoxine-Pyrimethamine + Amodiaquine (SPAQ)

Other names:

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.

Arms:

Sulfadoxine-Pyrimethamine + Amodiaquine (SPAQ)

Other names:

Size

3575

Primary endpoint

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

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

One month

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

One month

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

One month

Eligibility criteria

Inclusion Criteria: * 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. * Children with HIV * Previous treatment with Amodiaquine in the past 28 days (treatment with ASAQ or SPAQ)

Protocol

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE3'], 'designInfo': {'allocation': 'NON_RANDOMIZED', 'interventionModel': 'PARALLEL', 'primaryPurpose': 'PREVENTION', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 3575, 'type': 'ESTIMATED'}}

Updated at

2024-03-25

1 organization

2 products

1 indication

Organization

Malaria Consortium

Product

Sulfadoxine pyrimethamine

Indication

Malaria

Product

Amodiaquine