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

NCT ID: NCT05471544

Last Updated: 2024-03-25

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 3575 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-07-18
• Study Completion Date: 2024-12-31

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.

Detailed Description

This is an implementation research study, using a Type II hybrid effectiveness-implementation study design, 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 its potential impact on health outcomes. Five monthly cycles of SMC will be implemented between June and October 2022 in one county, Aweil South, in Northern Bahr el Gazal state.

The study will comprise the following six components :

1. Two cross-sectional surveys at the height of the malaria season to explore impact on malaria incidence

2. End-of-round survey

3. 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

4. Resistance markers study in children 3-59 months in the two research counties plus the two standard intervention counties to measure changes in resistance marker prevalence over time (pre and post within the same year and between years)

Conditions

Malaria

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Sulfadoxine-Pyrimethamine + Amodiaquine (SPAQ)

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

Group Type: EXPERIMENTAL

Sulfadoxine pyrimethamine

Intervention Type: 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.

Amodiaquine

Intervention Type: 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.

Control

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

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

SP; AQ

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)

• Minimum Eligible Age: 3 Months
• Maximum Eligible Age: 59 Months
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Malaria Consortium

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ahmed Ismail Julla

Role: PRINCIPAL_INVESTIGATOR

Ministry of Health, South Sudan

Locations

Aweil South

Aweil, Northern Bahr El Gazal, South Sudan

Countries

South Sudan

Other Identifiers

SMCSSPHASE1

Identifier Type: -

Identifier Source: org_study_id