Tripartite International Research for the Elimination of Trachoma

Phase 4

Completed

• Conditions: Chlamydia; Trachoma
• Interventions: Drug: mass treatment with oral azithromycin

• Registration Number: NCT01202331
• Lead Sponsor: University of California, San Francisco

Brief Summary

Mass antimicrobial administrations have been remarkably successful in reducing the prevalence of the ocular strains of Chlamydia that cause trachoma. Repeated distributions progressively lower the prevalence of infection, and in some cases may even result in local elimination. Mass treatments cannot be continued forever, due to concerns about cost and antibiotic resistance. The hope has been that other measures such as latrine construction and hygiene programs would prevent infection from returning. Unfortunately, no non-antibiotic measure has yet demonstrated an effect on infection.

1. We hypothesize that Chlamydial infection will return to communities when treatment ends.

2. We hypothesize that infection will be completely eliminated in all communities treated for seven years.

3. We hypothesize that identifying and treating clinically active cases among preschool aged children will delay or even prevent reemergence at a far lower cost than mass treatment of all individuals.

Detailed Description

The proposed study is a group-randomized trial to determine the frequency and treatment target of community-wide mass antibiotic treatment to eliminate trachoma. We will continue to monitor a sub-set of communities from our TANA study, in Goncha Siso Enese district of East Gojam Zone, Ethiopia. Here we evaluate how infection returns when antibiotics are discontinued, whether infection can be predictably eliminated, and whether infection can be prevented from returning with targeted treatment strategies:

Specific Aim 1. To determine whether antibiotics can be stopped after 4 years.

Specific Aim 2. To determine whether infection can be completely eliminated if mass treatments continue for seven years.

Specific Aim 3. To determine whether treatment targeted to pre-school aged children, or to households in which a pre-school aged child has clinically active trachoma, will prevent infection from returning into the community.

Specific Aim 4: To determine whether mass azithromycin distributions reduce visits to local health clinics due to all causes and infectious causes.

Specific Aim 5: To determine whether mass azithromycin distributions result in better growth metrics (weight-for-height, height-for age, weight-for-age, middle upper arm circumference) compared to no treatment.

Specific Aim 6: To determine whether under-5 mortality is lower in communities treated with mass azithromycin compared to no treatment

Specific Aim 7: To determine whether macrolide resistance in Streptococcus pneumoniae, Hameophilus influenzae, and Staphylococcus aureus is more prevalent in communities treated with biannual mass azithromycin compared to communities treated with annual mass azithromycin, and to determine whether targeted azithromycin treatments result in less macrolide resistance compared to mass azithromycin distributions.

Study Timeline

• Study First Submitted: 2010-09-13
• Study First Submitted QC: 2010-09-13
• Study First Posted: 2010-09-15
• Study Start: 2010-11
• Primary Completion: 2013-11
• Study Completion: 2014-05
• Status Verified: 2017-10
• Last Update Submitted: 2017-10-09
• Last Update Posted: 2017-10-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 29000

Inclusion Criteria

• All residents residing in the state-teams which are randomly selected for this study.

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Exclusion Criteria

• Pregnant women
• Children under 6 months of age
• All those who are allergic to macrolides or azalides
• Refusal of village chief (for village inclusion), or refusal of parent or guardian (for individual inclusion)

Individuals in these three exclusion criteria will not be given the study antibiotic azithromycin, but offered the current WHO-recommended alternative treatment to azithromycin for active trachoma, which is 1% tetracycline eye ointment, to be used twice a day, topically to both eyes, for six weeks. Note that the exclusion criteria refer to the exclusion to the treatment drug, but not to the monitoring, treatment of trachoma, and examinations.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
O	mass treatment with oral azithromycin	Targeted Treatment by Clinical Exam
L	mass treatment with oral azithromycin	Continue Annual Treatment
M	mass treatment with oral azithromycin	Continue Biannual Treatment
N	mass treatment with oral azithromycin	Targeted Treatment by Age

Primary Outcome Measures

Name	Time	Method
The average prevalence of ocular chlamydia infection in communities in an arm as determined by pooled NAAT (Nucleic Acid Amplification Test)(at 36 months versus 0 months for Aim 1, at 36 months for Aim 2 and Aim 3)	36 months

Secondary Outcome Measures

Name	Time	Method
Clinical active trachoma in community, as determined by the WHO simplified grading system	36 months
Macrolide resistance in pneumococcus, Haemophilus influenzae, and Staphylococcus aureus (% resistance over time, clustered by randomization unit)	36 months
Childhood mortality (6 months -5 years of age), 6-10 years of age, and >10 years	36 months
Health clinic visits (due to all causes and due to infectious causes) in children aged 6 months-5 years, 6-10 years, and >10 years	36 months
Prevalence of anemia (hemoglobin levels in 0-9 year olds) and the prevalence of malaria	36 months
Estimate of chlamydial load from real-time, qPCR	0, 12, 24, 36 months
Anthropometric measurements (weight and height), as outlined by WHO child growth standards (0-5 years of age)	3, 12, 24, and 36 months after baseline
Clinically active trachoma in a school (all children under age 10), as determined by the WHO simplified grading system	36 months
Cost-effectiveness of mass azithromycin administration, per infection year prevented and cost per eliminated village	0, 12, 24, and 36 months

Trial Locations

Locations (1)

The Carter Center, Ethiopia; 🇪🇹 Addis Ababa, Ethiopia