Trachoma Elimination Study by Focused Antibiotic (TESFA)

Study Overview
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Brief Summary
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The study population consists of all households residing in eligible kebeles (sub-districts) within districts in Amhara National Regional State which are identified as having a high prevalence of trachoma and infection measured from recent trachoma impact assessments. Within each study kebele, one village will be randomly selected to serve as the sentinel study site for that kebele. Once these villages are chosen, the study team will use government-provided census records, or perform a census in each village, and will randomly choose 50 children to serve as the sentinel children for the study. After the baseline visit, all kebeles will be randomized into one of the two treatment arms to either receive standard-or-care treatment, which is an annual community-wide mass drug administration (MDA), or the enhanced antibiotic treatment. Recruitment will take place at the selected children's household. Oral informed consent will be sought from village leader/chairmen before surveys are conducted in a village. Oral informed consent will then be obtained from household heads of those houses included in the study; and then from each participating individual. Oral consents will be obtained given the low literacy rates in rural Amhara. Data collection will occur at baseline, week 4, month 12, and month 24 in both arms of the study. A head of household will be asked a series of household level questions, which will be followed by a household-level census, where all consenting participants residing in the selected households will have their eyes examined for trachoma signs. This is a non-invasive procedure whereby a trained trachoma grader flips each eyelid and examines for trachoma signs. Lastly, the selected child and one randomly selected adult will have their right eye lid swabbed for evidence of trachoma infection. The total estimated respondent burden is 30 to 45 minutes.

Detailed Description
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Trachoma, caused by ocular infection with Chlamydia trachomatis, is one of the leading causes of preventable blindness worldwide with 51 countries known or suspected to be endemic for blinding trachoma. The World Health Organization (WHO) has recommended the Surgery, Antibiotic treatment, promotion of Facial cleanliness and hygiene, and Environmental improvement (SAFE) strategy for trachoma control. Annual mass drug administration (MDA) with the antibiotic azithromycin to treat trachoma is effective, at least in areas with moderate to low levels or trachoma. This has not been the experience in regions with high levels of trachoma including Amhara, Ethiopia. After 8 rounds of annual MDA, trachoma remains stubbornly high throughout the region. Given this experience from the Amhara region of Ethiopia, The Carter Center will work with local government partners at the regional, zonal, district, and sub-district levels to assess the effectiveness of a targeted antibiotic treatment regimen on trachoma prevalence by using a cluster randomized, controlled trial design with the understanding that increasing the need for drug in the short-term to intensify impact, may result in reduced need for drug in the long-term. The effectiveness of this alternative treatment regimen will be assessed over a period of 2 years by periodically evaluating trachoma outcomes throughout study communities. The key objectives of this study are to: To determine the effectiveness of an enhanced antibiotic treatment regimen characterized by a community-wide MDA followed by two rounds of targeted (to children age 2 to 9 years) treatment in quick succession (1-2 weeks apart) compared to annual standard-of-care MDA. To determine the added cost and cost-effectiveness of an enhanced antibiotic treatment regimen compared to annual standard-of-care MDA.

Official Title
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Trachoma Elimination Study by Focused Antibiotic (TESFA): The Impact of an Enhanced Antibiotic Treatment Regimen on Trachoma in Amhara, Ethiopia

Conditions
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Trachoma

Intervention / Treatment
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* Drug: Azithromycin mass treatment
* Drug: Azithromycin targeted treatment


Participation Criteria
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Eligibility Criteria
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Cluster (kebele) Inclusion Criteria: The kebele must be located in Amhara and eligible for annual MDA with azithromycin under WHO treatment guidelines. Located within targeted districts where the prevalence of TF is high (at least 30%) and the prevalence of CT infection is suspected to be high (10% if possible) measured from the most recent trachoma impact assessment. The kebele representatives consent to participation in the trial. Gott (village) Inclusion Criteria: At least 50 children residing in the gott. Child Inclusion Criteria: Must reside in a cluster selected for this study. Must have a head of household or designated adult-in-charge who can provide consent for that child to be included in the study sample and to consent to allowing study staff to collect an ocular swab from the conjunctival epithelium. Child must assent to having a swab taken. Child must not have an ocular condition which would preclude grading trachoma or taking an ocular specimen. Exclusion Criteria: none

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 9 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: Parallel Assignment
Interventional Model Description: Sixty-four kebeles (sub-districts) of Amhara will be randomized to receive annual mass treatment or annual mass treatment plus targeted treatment. One gott (village) per kebele will be selected and 50 children from each gott will be randomly selected.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Azithromycin mass treatment<br>Persons living in regions randomized to this arm will receive mass drug administration (MDA) of azithromycin per the current annual MDA schedule. | Drug: Azithromycin mass treatment<br>* Standard of care annual community-wide mass drug administration (MDA) will be provided at the normally scheduled time.<br>* Other names: Zithromax;|
| Experimental: Azithromycin mass treatment plus targeted treatment<br>In addition to azithromycin administration per the current annual MDA schedule, children in regions randomized to this arm will receive azithromycin targeted treatment. | Drug: Azithromycin mass treatment<br>* Standard of care annual community-wide mass drug administration (MDA) will be provided at the normally scheduled time.<br>* Other names: Zithromax;Drug: Azithromycin targeted treatment<br>* Two rounds of treatment targeted to all children aged 2 to 9 years old. The first targeted round will be 1-2 weeks after the community-wide MDA and the second round will occur another 1-2 weeks later.<br>* Other names: Zithromax;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prevalence of Chlamydia trachomatis (CT) infection | The community-level prevalence of CT infection in children aged 6 months to 9 years will be compared between study arms. | Month 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in prevalence of trachomatous inflammation-follicular (TF) | The prevalence of trachomatous inflammation-follicular (TF) among all household members will be noted at each visit and compared between study arms. | Baseline, Week 4, Month 12, Month 24 | 
| Change in prevalence of trachomatous inflammation-intense (TI) | The prevalence of trachomatous inflammation-intense (TI) among all household members will be noted at each visit and compared between study arms. | Baseline, Week 4, Month 12, Month 24 | 
| Change in Chlamydia trachomatis (CT) infection in children | The change in prevalence of Chlamydia trachomatis (CT) infections in children ages 6 months to 9 years will be compared between study arms. Analysis will be conducted which will include all three of these time-points to compare infection prevalence between the comparison arms | Baseline, Month 12, Month 24 | 
| Prevalence of Chlamydia trachomatis (CT) infection among adults | The prevalence of Chlamydia trachomatis (CT) infection among adults will be compared between study arms. | Month 12 | 
| Cost | The cost of the enhanced intervention will be compared to the cost of the standard-of-care intervention. | Month 24 | 
| Cost-effectiveness | The cost-effectiveness of the enhanced intervention will be compared to the cost of the standard-of-care intervention. The incremental cost effectiveness analysis ratio approach will be used. Effectiveness is defined as the percent CT reduction from baseline to 24 months and the outcome of this analysis will be the cost per percent of CT infection reduction. | Month 24 | 
| Correlation between Chlamydial Infection and trachomatous inflammation-follicular (TF) and trachomatous inflammation-intense (TI) | We will conduct cluster level analysis using cluster level Ct and clinical data including TF and TI. | Baseline, Week 4, Month 12, Month 24 | 
| Cluster-level Chlamydial load | Infectious load for all individual specimens from children aged 6 months to 9 years who test positive for CT will be measured for chlamydia load. Chlamydial load will be noted at each visit and compared between study arms. | Baseline, Week 4, Month 12, Month 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Antibiotics, Infectious diseases, Tropical medicine, Public health