Partnership for Rapid Elimination of Trachoma

Trachoma Clinical Trial

— PRET  

Official title:

Research to Programs for Trachoma Elimination: Antibiotic Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00792922
• Other study ID #: NA_00018439
• Status: Completed
• Phase: Phase 4
• First received: November 17, 2008
• Last updated: April 6, 2015
• Start date: May 2008
• Est. completion date: June 2014

Study information

• Verified date: April 2015
• Source: Johns Hopkins University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review BoardTanzania: National Institute for Medical ResearchGambia: MRC Ethics Committee
• Study type: Interventional

Clinical Trial Summary

Trachoma, an ocular infection caused by C. trachomatis, is the second leading infectious cause of blindness worldwide. Years of repeated infection with C. trachomatis cause the eyelid to scar and contract and ultimately to rotate inward such that the eyelashes rub against the eyeball and abrade the cornea (trichiasis). The World Health Organization (WHO) has endorsed a multi-faceted strategy to combat trachoma, which includes the use of antibiotic treatment to reduce the community pool of infection with C. trachomatis. The objective of this study is to conduct a randomized, community-based trial in three countries (Niger, Tanzania and The Gambia), representing different baseline endemicities, of alternative coverages and frequencies of administration of mass antibiotic treatment as well as to determine the cost-effectiveness of these different strategies from a program perspective.

Description:

A randomized, 2x2 factorial designed trial will be implemented in each of the three countries. Communities will be randomized to two different coverage targets (80%-89% versus ≥90%) for three years of mass treatment.

In The Gambia and Tanzania, communities will be further randomized to yearly mass treatment versus mass treatment at baseline followed by yearly mass treatment only if trachoma prevalence in sentinel children is greater than 5%. The communities will continue to be followed and treatment will resume if trachoma prevalence is found to be 20% or greater at the 12 or 18 month surveys.

In Niger, communities will be randomized to the different coverage levels for annual mass azithromycin distribution and further randomized to biannual treatment at the two coverage targets for children ages twelve or younger.

Cross-sectional rates of trachoma and infection will be determined by examining sentinel children, age five years or younger, randomly selected from each community based on a community census. The census will be updated each year, and villages will be monitored at baseline, 6, 12, 18, 24, 30, and 36 months for infection and clinical disease.

The three-year study is in accord with the WHO guidelines which recommend three years of annual mass treatment followed by a re-survey to determine need for further treatment. We will evaluate the efficacy of guiding further mass treatment according to a laboratory test for Chlamydia or WHO guidelines. Where we estimate communities have infection rates less than 5% in sentinel children, or TF rates less than 5%, the community will be "graduated" from further mass treatment and followed for up to three years to look for evidence of re-emergent infection and disease. If rates of infection are found to be 20% or more return at the 12 or 18 month survey, mass treatment will be re-initiated.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20586
• Est. completion date: June 2014
• Est. primary completion date: June 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: N/A to 12 Years

Eligibility

Inclusion criteria for communities:

1. Communities are located in the target districts and accessible by vehicle

2. The community leaders consent to have the community enrolled

3. Rapid assessment and/or available data suggest trachoma rates are higher than 20% in the community.

4. The community size is <5,000 persons or >250 persons.

If a community meets the inclusion criteria and community leaders consent to have the community enrolled, then sentinel children will be selected based on the following criteria:

1. The child is age 5 years or younger

2. The child must be a resident in an eligible, sample community (defined as either living in the community since birth, or moved in with parents or guardians).

3. The child must not have an ocular condition that would preclude grading trachoma or taking an ocular specimen.

4. The child must be willing to have a swab taken as part of being a sentinel child (this is critical for The Gambia and Tanzania, as each swab result counts towards meeting the stopping rule)

5. The child must have an identifiable guardian capable of providing consent to participate.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Factorial Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Trachoma

Intervention

Drug:
• Azithromycin
Comparison of community coverage rate
• Azithromycin
Comparison of coverage levels at baseline treatment followed by annual treatment if prevalence of trachoma is >5%. In Niger, there will be a comparison of coverage levels in everyone versus in children ages twelve and under who are treated every 6-months.

Locations

Country	Name	City	State
United Kingdom	London School of Hygiene and Tropical Medicine	London
United States	Johns Hopkins University	Baltimore	Maryland
United States	UCSF Proctor Foundation	San Francisco	California

Sponsors (2)

Lead Sponsor	Collaborator
Johns Hopkins University	Bill and Melinda Gates Foundation

Countries where clinical trial is conducted

United States,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Community prevalence of trachoma and ocular C. trachomatis infection		5 years	No
Secondary	Community costs of mass treatment		5 years	No
Secondary	Community costs of incident infection		5 years	No
Secondary	Macrolide resistance in pneumococcus (% resistance over time, clustered by randomization unit)	PRET Niger	36 months	No
Secondary	Anthropometric measurements (WHZ, WAZ, HAZ, MUACZ), as outlined by WHO child growth standards (0-5 years of age)	PRET Niger	12-36 months after baseline	No
Secondary	Prevalence of anemia (hemoglobin levels in 0-5 year olds) and the prevalence of malaria	PRET Niger	12 - 36 months after baseline	No
Secondary	Mortality in 1-5 year old study children	PRET Gambia	Over study period	No
Secondary	Cause-specific mortality in 1-5 year olds assessed by verbal autopsy	PRET Gambia	Over study period	No
Secondary	Mortality in adults in the study area	PRET Gambia	Over study period	No
Secondary	Cause-specific mortality in adults assessed by verbal autopsy	PRET Gambia	Over study period	No
Secondary	Morbidity among 1-5 year old study children as assessed by height for age, weight for age, weight for height, body mass index and Hackett spleen size	PRET Gambia	30 months after baseline	No
Secondary	Serotype distribution, antibiotic sensitivity profile and MLST type of Streptococcus pneumoniae carried in the nasopharynx of study children	PRET Gambia	30 months after baseline	No
Secondary	Rates of health clinic visits overall, for infectious diseases, diarrhea, malaria, respiratory disease, and antibiotics distributed	PRET Niger	12, 24, and 36 months after baseline	No
Secondary	Mortality in children	PRET Niger	Over study period	No
Secondary	Mortality in adults	PRET Niger	Over study period	No