Trachoma Amelioration in Northern Amhara (TANA)

Sponsor

University of California, San Francisco (Other)

Overall Status

Completed

CT.gov ID

NCT00322972

Collaborator

(none)

33,000

Enrollment

Location

Arms

Duration (Months)

347.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The WHO has initiated a program to eliminate trachoma, blinding eye infection caused by Chlamydia trachomatis, in large part by mass distributions of oral azithromycin. The proposed study will determine the frequency and treatment target of community-wide mass antibiotic treatment. We will also study the impact of mass antibiotic distribution on antibiotic-resistance in pneumococcus.

Condition or Disease	Intervention/Treatment	Phase
Trachoma Chlamydia	Drug: Mass treatment with oral azithromycin to an entire community	Phase 4

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 also study the impact of community-wide antibiotic distribution on antibiotic-resistance in pneumococcus. Communities in Goncha Siso Enese district of East Gojam Zone, Ethiopia will be randomly assigned to different treatment schemes and monitored to study the following research questions:

Specific Aim 1. To determine whether biannual mass treatments is more likely to eliminate ocular chlamydia from hyper-endemic communities than annual mass treatments.

Specific Aim 2. To determine whether children form a core group for the transmission of trachoma.

Specific Aim 3. To determine whether latrine construction prevents the return of infection into a community after mass treatment.

Specific Aim 4. To determine the effect of mass azithromycin treatments on antibiotic resistance in pneumococcus and the reduction in mortality.

Specific Aim 5. To determine whether annual mass treatments are more likely to eliminate ocular chlamydia from hyper-endemic communities than biennial mass treatments.

Study Design

Study Type:

Interventional

Actual Enrollment :

33000 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Eliminating Trachoma With Repeat Mass Drug Treatment

Study Start Date :

Jun 1, 2006

Actual Primary Completion Date :

Nov 1, 2009

Actual Study Completion Date :

May 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Other: A Annual mass treatment	Drug: Mass treatment with oral azithromycin to an entire community 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. For study arm C and D, nasopharyngeal swabs will be collected from 10 randomly selected children among the 60 participants under 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.
Other: B Biannual mass treatment	Drug: Mass treatment with oral azithromycin to an entire community 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. For study arm C and D, nasopharyngeal swabs will be collected from 10 randomly selected children among the 60 participants under 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.
Experimental: C Mass administration of antibiotic; treatment of children (1-10 years of age) only	Drug: Mass treatment with oral azithromycin to an entire community 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. For study arm C and D, nasopharyngeal swabs will be collected from 10 randomly selected children among the 60 participants under 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.
No Intervention: D Delayed initiation of mass administration of antibiotic
Other: F One-time mass administration only	Drug: Mass treatment with oral azithromycin to an entire community 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. For study arm C and D, nasopharyngeal swabs will be collected from 10 randomly selected children among the 60 participants under 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.
Experimental: G One-time mass administration of antibiotics, plus intensive latrine construction	Drug: Mass treatment with oral azithromycin to an entire community 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. For study arm C and D, nasopharyngeal swabs will be collected from 10 randomly selected children among the 60 participants under 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.

Outcome Measures

Primary Outcome Measures

The average prevalence of ocular chlamydia infection in communities in an arm as determined by pooled NAAT (Nucleic Acid Amplification Test)(at 42 months for Aim 1, at 12 months for Aim 2, post-treatment relative to pre-treatment for Aim 3) [42 months]

Secondary Outcome Measures

Clinical active trachoma in community, as determined by the WHO simplified grading system [42 months]
Childhood (>= 1 year of age) mortality, analyzed as 1-5, 6-10 years of age, and total [42 months]
Macrolide resistance in pneumococcus (% resistance over time, clustered by randomization unit) [42 months]
Average prevalence of ocular chlamydia infection in annually and biennially treated communities as determined by pooled NAAT (Nucleic Acid Amplification Test) [48 months]
Diversity measure in the conjunctival and nasopharyngeal microbiomes of children (age 0-9) [0, 6, 12, 18, 24, 30, 36, 42, and 48 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

1 Year and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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.