Trachoma Amelioration in Northern Amhara (TANA) - Full Text View

Purpose

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	Intervention	Phase
Trachoma Chlamydia	Drug: Mass treatment with oral azithromycin to an entire community	Phase 4

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Single Blind (Outcomes Assessor) Primary Purpose: Treatment
Official Title:	Eliminating Trachoma With Repeat Mass Drug Treatment

Resource links provided by NLM:

MedlinePlus related topics: Antibiotics Bacterial Infections Chlamydia Infections Eye Diseases Eye Infections

Drug Information available for: Azithromycin Azithromycin dihydrate Azithromycin monohydrate

U.S. FDA Resources

Further study details as provided by University of California, San Francisco:

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) [ Time Frame: 42 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Clinical active trachoma in community, as determined by the WHO simplified grading system [ Time Frame: 42 months ] [ Designated as safety issue: No ]
Childhood (>= 1 year of age) mortality, analyzed as 1-5, 6-10 years of age, and total [ Time Frame: 42 months ] [ Designated as safety issue: No ]
Macrolide resistance in pneumococcus (% resistance over time, clustered by randomization unit) [ Time Frame: 42 months ] [ Designated as safety issue: No ]
Average prevalence of ocular chlamydia infection in annually and biennially treated communities as determined by pooled NAAT (Nucleic Acid Amplification Test) [ Time Frame: 48 months ] [ Designated as safety issue: No ]

Estimated Enrollment:	36000
Study Start Date:	June 2006
Estimated Study Completion Date:	May 2014
Primary Completion Date:	November 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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.
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
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.

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.

Eligibility

Ages Eligible for Study:	1 Year and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00322972

Locations

Ethiopia
Carter Center, Ethiopia
Addis Ababa, Ethiopia

Sponsors and Collaborators

University of California, San Francisco

Investigators

Principal Investigator:	Tom Lietman, MD	Proctor Foundation, UCSF
Study Director:	Nicole Stoller, MPH	Proctor Foundation, UCSF
Study Director:	Sintayehu Gebresillasie, MSc	Carter Center, Ethiopia
Study Director:	Paul Emerson, MD	Emory University

More Information

Publications:

House JI, Ayele B, Porco TC, Zhou Z, Hong KC, Gebre T, Ray KJ, Keenan JD, Stoller NE, Whitcher JP, Gaynor BD, Emerson PM, Lietman TM. Assessment of herd protection against trachoma due to repeated mass antibiotic distributions: a cluster-randomised trial. Lancet. 2009 Mar 28;373(9669):1111-8.

Gebre T, Ayele B, Zerihun M, Genet A, Stoller NE, Zhou Z, House JI, Yu SN, Ray KJ, Emerson PM, Keenan JD, Porco TC, Lietman TM, Gaynor BD. Comparison of annual versus twice-yearly mass azithromycin treatment for hyperendemic trachoma in Ethiopia: a cluster-randomised trial. Lancet. 2012 Jan 14;379(9811):143-51. Epub 2011 Dec 20.

Stoller NE, Gebre T, Ayele B, Zerihun M, Assefa Y, Habte D, Zhou Z, Porco TC, Keenan JD, House JI, Gaynor BD, Lietman TM, Emerson PM. Efficacy of latrine promotion on emergence of infection with ocular Chlamydia trachomatis after mass antibiotic treatment: a cluster-randomized trial. Int Health. 2011 Jun;3(2):75-84.

Skalet AH, Cevallos V, Ayele B, Gebre T, Zhou Z, Jorgensen JH, Zerihun M, Habte D, Assefa Y, Emerson PM, Gaynor BD, Porco TC, Lietman TM, Keenan JD. Antibiotic selection pressure and macrolide resistance in nasopharyngeal Streptococcus pneumoniae: a cluster-randomized clinical trial. PLoS Med. 2010 Dec 14;7(12):e1000377.

Porco TC, Gebre T, Ayele B, House J, Keenan J, Zhou Z, Hong KC, Stoller N, Ray KJ, Emerson P, Gaynor BD, Lietman TM. Effect of mass distribution of azithromycin for trachoma control on overall mortality in Ethiopian children: a randomized trial. JAMA. 2009 Sep 2;302(9):962-8.

Keenan JD, Ayele B, Gebre T, Zerihun M, Zhou Z, House JI, Gaynor BD, Porco TC, Emerson PM, Lietman TM. Childhood mortality in a cohort treated with mass azithromycin for trachoma. Clin Infect Dis. 2011 Apr 1;52(7):883-8.

Lietman TM, Gebre T, Ayele B, Ray KJ, Maher MC, See CW, Emerson PM, Porco TC; TANA Study Group. The epidemiological dynamics of infectious trachoma may facilitate elimination. Epidemics. 2011 Jun;3(2):119-24. Epub 2011 Apr 6.

Stoller NE, Gebre T, Ayele B, Zerihun M, Assefa Y, Habte D, Zhou Z, Porco TC, Keenan JD, House JI, Gaynor BD, Lietman TM, Emerson PM. Efficacy of latrine promotion on emergence of infection with ocular Chlamydia trachomatis after mass antibiotic treatment: a cluster-randomized trial. Int Health. 2011 Jun;3(2):75-84.

Keenan JD, See CW, Moncada J, Ayele B, Gebre T, Stoller NE, McCulloch CE, Porco TC, Gaynor BD, Emerson PM, Schachter J, Lietman TM. Diagnostic characteristics of tests for ocular Chlamydia after mass azithromycin distributions. Invest Ophthalmol Vis Sci. 2012 Jan 25;53(1):235-40. Print 2012 Jan.

Gebre T, Ayele B, Zerihun M, House JI, Stoller NE, Zhou Z, Ray KJ, Gaynor BD, Porco TC, Emerson PM, Lietman TM, Keenan JD. Latrine promotion for trachoma: assessment of mortality from a cluster-randomized trial in Ethiopia. Am J Trop Med Hyg. 2011 Sep;85(3):518-23.

Responsible Party:	Thomas M. Lietman, Professor, University of California, San Francisco
ClinicalTrials.gov Identifier:	NCT00322972 History of Changes
Other Study ID Numbers:	10-02576
Study First Received:	May 5, 2006
Last Updated:	May 20, 2013
Health Authority:	United States: Institutional Review Board Ethiopia: Ethiopia Science and Technology Commission

Keywords provided by University of California, San Francisco:

Bacterial Infections
Chlamydia Infections
Eye Diseases

Additional relevant MeSH terms:

Chlamydia Infections
Trachoma
Chlamydiaceae Infections
Gram-Negative Bacterial Infections
Bacterial Infections
Sexually Transmitted Diseases, Bacterial
Sexually Transmitted Diseases
Infection
Genital Diseases, Male
Genital Diseases, Female
Conjunctivitis, Bacterial

Eye Infections, Bacterial
Eye Infections
Conjunctivitis
Conjunctival Diseases
Eye Diseases
Corneal Diseases
Azithromycin
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on June 13, 2013