Tripartite International Research for the Elimination of Trachoma (TIRET)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Thomas M. Lietman, University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT01202331
First received: September 13, 2010
Last updated: July 1, 2014
Last verified: July 2014
  Purpose

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.

Condition Intervention Phase
Trachoma
Chlamydia
Drug: mass treatment with oral azithromycin
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: Tripartite International Research for the Elimination of Trachoma

Resource links provided by NLM:


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 36 months versus 0 months for Aim 1, at 36 months for Aim 2 and Aim 3) [ Time Frame: 36 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Clinical active trachoma in community, as determined by the WHO simplified grading system [ Time Frame: 36 months ] [ Designated as safety issue: No ]
  • Childhood mortality (6 months -5 years of age), 6-10 years of age, and >10 years [ Time Frame: 36 months ] [ Designated as safety issue: No ]
  • Macrolide resistance in pneumococcus, Haemophilus influenzae, and Staphylococcus aureus (% resistance over time, clustered by randomization unit) [ Time Frame: 36 months ] [ Designated as safety issue: No ]
  • Anthropometric measurements (weight for height), as outlined by WHO child growth standards (0-5 years of age) [ Time Frame: 3, 12, 24, and 36 months after baseline ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: 36 months ] [ Designated as safety issue: No ]
  • Prevalence of anemia (hemoglobin levels in 0-9 year olds) and the prevalence of malaria [ Time Frame: 36 months ] [ Designated as safety issue: No ]
  • Clinically active trachoma in a school (all children under age 10), as determined by the WHO simplified grading system [ Time Frame: 36 months ] [ Designated as safety issue: No ]
  • Cost-effectiveness of mass azithromycin administration, per infection year prevented and cost per eliminated village [ Time Frame: 0, 12, 24, and 36 months ] [ Designated as safety issue: No ]
  • Estimate of chlamydial load from real-time, qPCR [ Time Frame: 0, 12, 24, 36 months ] [ Designated as safety issue: No ]

Enrollment: 29000
Study Start Date: November 2010
Study Completion Date: May 2014
Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
No Intervention: J
Stop Annual Treatment
No Intervention: K
Stop Biannual Treatment
L
Continue Annual Treatment
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.
Other Name: Zithromax
M
Continue Biannual Treatment
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.
Other Name: Zithromax
Experimental: N
Targeted Treatment by Age
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.
Other Name: Zithromax
Experimental: O
Targeted Treatment by Clinical Exam
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.
Other Name: Zithromax

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.

  Eligibility

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01202331

Locations
Ethiopia
The Carter Center, Ethiopia
Addis Ababa, Ethiopia
Sponsors and Collaborators
University of California, San Francisco
Investigators
Principal Investigator: Tom Lietman, MD F.I. Proctor Foundation, UCSF
Study Director: Nicole Stoller, MPH F.I. Proctor Foundation, UCSF
Study Director: Sintayehu Gebresillasie, MSc The Carter Center, Ethiopia
Study Director: Paul Emerson, PhD The Carter Center, Atlanta
  More Information

No publications provided

Responsible Party: Thomas M. Lietman, Professor, University of California, San Francisco
ClinicalTrials.gov Identifier: NCT01202331     History of Changes
Other Study ID Numbers: 10-02169
Study First Received: September 13, 2010
Last Updated: July 1, 2014
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 August 20, 2014