Enhancing the A in SAFE for Trachoma

Emory University

Status and phase: Completed; Phase 4

Conditions: Trachoma

Treatments: Drug: Azithromycin for Second Community-wide MDA; Drug: Azithromycin for Routine Community-wide MDA; Drug: Two Additional Rounds of Azithromycin for Children

Study type: Interventional

Funder types: Other

Identifiers

NCT05634759

STUDY00002467

Details and patient eligibility

About

This study will assess the cost and feasibility of two strategies of enhanced Mass Drug Administration (MDA) of Zithromax to treat trachoma in the Republic of South Sudan. The secondary objectives of this study are to measure trachoma infection outcomes during the 12-month follow-up period among children up to 9 years of age.

Full description

Trachoma is an ocular disease caused by the bacterium Chlamydia trachomatis. The World Health Organization (WHO) has recently targeted trachoma for global elimination as a public health problem by 2030. Though progress has been made in reducing the burden of trachoma in many endemic countries, those affected by conflict and humanitarian emergencies have been left behind and will likely take decades to reach trachoma elimination targets. To "catch-up", these countries must consider enhancements to the surgery, antibiotic, facial cleanliness, and environmental improvement (SAFE) strategy.

Evidence for the importance of enhanced mass drug administration (MDA) strategies is growing, particularly with the help of modeling studies. Recent work by the neglected tropical disease (NTD) modeling consortium has recently demonstrated that in some hyperendemic districts, annual MDA will not result in a district reaching the elimination as a public health problem threshold within 10 years. Delays in implementation whether due to insecurity or to coronavirus disease 2019 (COVID-19) would likely lead to higher prevalence trachoma prevalence in these districts for years to come. However, when testing alternative MDA strategies, modelers found that the annual trajectory of trachoma prevalence could be changed. One MDA alternative characterized by a community-wide MDA followed by two extra rounds of treatment to children aged 2 to 9 years 1 week and again 3 weeks after the normal community wide MDA, demonstrated a considerable faster time to elimination compared to standard of care. Empirical data from the field under different alternative MDA strategies are needed to verify these modeling results.

The Republic of South Sudan has historically had one of the highest burdens of trachoma in the world. Currently the county has many districts considered highly endemic, and therefore reaching the elimination of trachoma as a public health problem by the year 2030 will likely be a large challenge. Based on 2015 trachoma prevalence data, trachomatous inflammation-follicular among children ages 1 to 9 years ranged from 30% to 48% across three Kapoeta counties in Eastern Equatoria state, Republic of South Sudan and trachomatous trichiasis ranged from 2.6% to 3.7% in those ages 15 years and above, both indicators above WHO elimination thresholds. The Republic of South Sudan Ministry of Health, with support from The Carter Center, has been implementing the SAFE strategy in these three counties (Kapoeta North, Kapoeta South, and Kapoeta East) for over 10 years. Interventions have included the provision of surgery, conducting MDA, and providing health education. All three counties conducted their fifth consecutive annual round of MDA between October 2020 to December 2020 and will therefore be scheduled to conduct an impact survey in 2021.

Thirty villages in the Republic of South Sudan will be randomized to participate in one of two enhanced MDA strategies. Enhanced MDA strategy 1 consists of a routine community-wide MDA followed by two additional rounds targeted to children age 6 months to 9 years. The additional rounds of treatment will occur 2 weeks apart and will begin 1 week after the community-wide MDA. Enhanced MDA Strategy 2 consist of a routine community-wide MDA followed by a second community-wide MDA approximately 6-8 months later. Participants will be followed for 12 months.

Enrollment: 34,630 patients

Sex: All

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria for Villages:

• The village must be located in a district eligible for annual MDA with azithromycin under WHO treatment guidelines.
• The village representatives' consent to participation in the study. Individual consent will also be obtained for each individual within the study.

Inclusion Criteria for Children in Enhanced MDA Strategy 1:

• Children aged 6 months to 9 years of age
• Consent for child inclusion is obtained by the parent/guardian and adequate provisions are made to solicit assent from the child.

Exclusion Criteria:

• none

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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34,630 participants in 3 patient groups

Routine Community-wide MDA followed by Two Additional Rounds of Treatment for Children

Experimental group

Description:

The enhanced MDA Strategy 1 consists of a routine community-wide MDA followed by two additional rounds targeted to children age 6 months to 9 years. The additional rounds of treatment will occur 2 weeks apart and will begin 1 week after the community-wide MDA.

Treatment:

Drug: Two Additional Rounds of Azithromycin for Children

Drug: Azithromycin for Routine Community-wide MDA

Routine Community-wide MDA followed by a Second Community-wide MDA

Experimental group

Description:

The enhanced MDA Strategy 2 consist of a routine community-wide MDA followed by a second community-wide MDA approximately 6-8 months later. The timing of the second MDA will depend on local conditions and logistical concerns.

Treatment:

Drug: Azithromycin for Routine Community-wide MDA

Drug: Azithromycin for Second Community-wide MDA

Standard-of-Care Annual MDA

Active Comparator group

Description:

Programmatic Control Comparator data for the standard-of-care annual MDA will come from the MDA conducted in 2022 in a random selection of 15 non-study villages.

Treatment:

Drug: Azithromycin for Routine Community-wide MDA