Partnership for Rapid Elimination of Trachoma

Study Overview
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Brief Summary
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Trachoma, an ocular infection caused by C. trachomatis, is the second leading infectious cause of blindness worldwide. Years of repeated infection with C. trachomatis cause the eyelid to scar and contract and ultimately to rotate inward such that the eyelashes rub against the eyeball and abrade the cornea (trichiasis). The World Health Organization (WHO) has endorsed a multi-faceted strategy to combat trachoma, which includes the use of antibiotic treatment to reduce the community pool of infection with C. trachomatis. The objective of this study is to conduct a randomized, community-based trial in three countries (Niger, Tanzania and The Gambia), representing different baseline endemicities, of alternative coverages and frequencies of administration of mass antibiotic treatment as well as to determine the cost-effectiveness of these different strategies from a program perspective.

Detailed Description
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A randomized, 2x2 factorial designed trial will be implemented in each of the three countries. Communities will be randomized to two different coverage targets (80%-89% versus ≥90%) for three years of mass treatment. In The Gambia and Tanzania, communities will be further randomized to yearly mass treatment versus mass treatment at baseline followed by yearly mass treatment only if trachoma prevalence in sentinel children is greater than 5%. The communities will continue to be followed and treatment will resume if trachoma prevalence is found to be 20% or greater at the 12 or 18 month surveys. In Niger, communities will be randomized to the different coverage levels for annual mass azithromycin distribution and further randomized to biannual treatment at the two coverage targets for children ages twelve or younger. Cross-sectional rates of trachoma and infection will be determined by examining sentinel children, age five years or younger, randomly selected from each community based on a community census. The census will be updated each year, and villages will be monitored at baseline, 6, 12, 18, 24, 30, and 36 months for infection and clinical disease. The three-year study is in accord with the WHO guidelines which recommend three years of annual mass treatment followed by a re-survey to determine need for further treatment. The investigators will evaluate the efficacy of guiding further mass treatment according to a laboratory test for Chlamydia or WHO guidelines. Where investigators estimate communities have infection rates less than 5% in sentinel children, or trachomatous inflammation (TF) ( rates less than 5%, the community will be graduated from further mass treatment and followed for up to three years to look for evidence of re-emergent infection and disease. If rates of infection are found to be 20% or more return at the 12 or 18 month survey, mass treatment will be re-initiated.

Official Title
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Research to Programs for Trachoma Elimination: Antibiotic Trial

Conditions
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Trachoma

Intervention / Treatment
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* Drug: Azithromycin
* Drug: Azithromycin


Participation Criteria
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Eligibility Criteria
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Inclusion criteria for communities: Communities are located in the target districts and accessible by vehicle The community leaders consent to have the community enrolled Rapid assessment and/or available data suggest trachoma rates are higher than 20% in the community. The community size is <5,000 persons or >250 persons. If a community meets the inclusion criteria and community leaders consent to have the community enrolled, then sentinel children will be selected based on the following criteria: The child is age 5 years or younger The child must be a resident in an eligible, sample community (defined as either living in the community since birth, or moved in with parents or guardians). The child must not have an ocular condition that would preclude grading trachoma or taking an ocular specimen. The child must be willing to have a swab taken as part of being a sentinel child (this is critical for The Gambia and Tanzania, as each swab result counts towards meeting the stopping rule) The child must have an identifiable guardian capable of providing consent to participate.

Ages Eligible for Study
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Maximum Age: 5 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Interventional Model Description: The study was a factorial study model to begin with in all 3 countries (Niger,Tanzania and Gambia) but because we never stopped treatment in Tanzania and Niger site.Hence the study design was collapsed to a simple design in Tanzania and Niger.The study model was kept as a factorial design for the Gambia site. Protocol Enrollment refers to the number of communities, not the number of participants enrolled.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: ≥90% coverage with azithromycin target<br>Selected communities will receive mass treatment annually for three years. | Drug: Azithromycin<br>* Comparison of community coverage rate<br>* Other names: Zithromax;|
| Active Comparator: 80%-89% coverage with azithromycin target<br>Selected communities will receive mass treatment annually for three years. | Drug: Azithromycin<br>* Comparison of community coverage rate<br>* Other names: Zithromax;|
| Active Comparator: ≥90% coverage with azithromycin , treatment based<br>Treatment to be administered at baseline then continued yearly if trachoma prevalence is greater than 5% In Niger, treatment will be every 6-months for children ages twelve and under. | Drug: Azithromycin<br>* Comparison of coverage levels at baseline treatment followed by annual treatment if prevalence of trachoma is >5%. In Niger, there will be a comparison of coverage levels in everyone versus in children ages twelve and under who are treated every 6-months.<br>* Other names: Zithromax;|
| Active Comparator: 80%-89% coverage with azithromycin : treatment based<br>Treatment to be administered at baseline then continued yearly if trachoma prevalence is greater than 5% In Niger, treatment will be every 6-months for children ages twelve and under. | Drug: Azithromycin<br>* Comparison of coverage levels at baseline treatment followed by annual treatment if prevalence of trachoma is >5%. In Niger, there will be a comparison of coverage levels in everyone versus in children ages twelve and under who are treated every 6-months.<br>* Other names: Zithromax;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Community Prevalence of Trachoma and Ocular C. Trachomatis (CT) Infection at Baseline | Mass drug administration (MDA) with azithromycin or topical tetracycline is recommended by World Health Organization (WHO) for 3 years in districts where the prevalence of trachoma is>=10 % in children aged 1-9 years. The prevalence of trachoma (TF) was measured using the Simplified WHO Grading System. Both eyelids were everted and tarsal conjunctiva graded for signs of clinical trachoma. Ocular photographs of right eye were taken on random samples of sentinel children to determine the drift in grading over time. To detect CT infection, an ocular swab of the right eye using a Dacron swab was collected from the sentinel kids. The swab was stored dry, and frozen until shipped and processed in the laboratory. Air control swabs were also taken to test for field and laboratory contamination. | At baseline | 
| Community Prevalence of Trachoma and Ocular C. Trachomatis (CT) Infection at 36 Months | 100 random sentinel children aged 0- 5 years per community were to be examined for prevalence of trachoma & CT infection in Tanzania & Gambia. 50-100 random sentinel children aged 0-5 years per community were to be examined in Niger per community for prevalence of TF and CT infection. Outcomes are reported at the community level because raw data could not be accessed. There is no way to determine how many participants were examined in each arm. | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Trachoma, Azithromycin, Mass treatment