Tripartite International Research for the Elimination of Trachoma

Chlamydia Clinical Trial

— TIRET  

Official title:

Tripartite International Research for the Elimination of Trachoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01202331
• Other study ID #: 10-02169
• Status: Completed
• Phase: Phase 4
• First received: September 13, 2010
• Last updated: October 9, 2017
• Start date: November 2010
• Est. completion date: May 2014

Study information

• Verified date: October 2017
• Source: University of California, San Francisco
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 29000
• Est. completion date: May 2014
• Est. primary completion date: November 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

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

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.

Related Conditions & MeSH terms

• Chlamydia
• Chlamydia Infections
• Trachoma

Intervention

Drug:
• mass treatment with oral azithromycin
For baseline and follow-up surveys prior to azithromycin distribution, a stratified random sample from two age groups will be chosen: 1) 60 study participants younger than 10 years old and 2) 60 study participants aged 10 years and above. Clinical examination will be performed and conjunctival swabs will be taken from all the study participants. Nasopharyngeal swabs will be collected in each community from 15 randomly selected children among the 60 participants under age 10 who were recruited for conjunctival swabbing. Then a single dose of azithromycin will be distributed according to study design: in tablet form for adults; a weight-adjusted tablet dose for children ages 8-10; and pediatric suspension for children ages 1 - 7.

Locations

Country	Name	City	State
Ethiopia	The Carter Center, Ethiopia	Addis Ababa

Sponsors (1)

Lead Sponsor	Collaborator
University of California, San Francisco

Country where clinical trial is conducted

Ethiopia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Clinical active trachoma in community, as determined by the WHO simplified grading system		36 months
Secondary	Childhood mortality (6 months -5 years of age), 6-10 years of age, and >10 years		36 months
Secondary	Macrolide resistance in pneumococcus, Haemophilus influenzae, and Staphylococcus aureus (% resistance over time, clustered by randomization unit)		36 months
Secondary	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
Secondary	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
Secondary	Prevalence of anemia (hemoglobin levels in 0-9 year olds) and the prevalence of malaria		36 months
Secondary	Clinically active trachoma in a school (all children under age 10), as determined by the WHO simplified grading system		36 months
Secondary	Cost-effectiveness of mass azithromycin administration, per infection year prevented and cost per eliminated village		0, 12, 24, and 36 months
Secondary	Estimate of chlamydial load from real-time, qPCR		0, 12, 24, 36 months