Azithromycin in Control of Trachoma II

April 12, 2012 updated by: Julius Schachter, University of California, San Francisco

Trachoma is the world's leading cause of preventable blindness. This disease, caused by Chlamydia trachomatis, is endemic in many parts of the developing world. In 1990s we evaluated the use of community-wide treatment with oral azithromycin in a project called Azithromycin in Control of Trachoma (ACT). This approach resulted in clinical improvement and dramatic reduction in prevalence of chlamydial infection through a 1-year follow-up. We enrolled the ACT villages, as well as an additional village that had not had any prior treatments, in our ACT II (2005) study and performed clinical surveys to assess trachoma activity testing conjunctival swabs for the presence of C. trachomatis by nucleic acid amplification tests (NAATs). Thus, we hoped to determine the long-term (10 year) effects of azithromycin treatment.

We have completed the census and clinical survey of the initial three villages. Mass treatment with azithromycin would not be justified with such low rates (1.8 - 4%) of ocular chlamydial infection. We have treated only those living in households with one or more cases of chlamydial infection and we will not follow up on these individually treated families.

In order to achieve the goals of our study, we now propose to identify other more remote villages with trachoma infection rates of 20% or more to evaluate the effect of community-wide treatment with single dose of oral azithromycin. If one or more of these villages (dependent upon population) has trachoma rates of 20% or more they will be invited to participate in the azithromycin treatment. In one set of subjects (1 or 2 villages, dependent upon population and infection rate) we will perform treatment, and follow them up at 2-, 12-, and 24-months post-treatment to ascertain infection rates. In a second set of subjects (1 or 2 villages, dependent upon population and infection rate) we will perform treatment, then perform re-treatment at 30-days post initial treatment, and follow them up at 2-, 12-, and 24-months post-treatment to ascertain infection rates. This should help us determine the need for/and the best time for re-treatment to eliminate blinding trachoma, as some recent studies suggest there is a 2-4% failure rate in the initial treatment. In sum, this study should provide a rational approach to use of community-wide azithromycin treatment to eliminate blinding trachoma as a public health problem

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Detailed Description

This is operational research aimed at better defining the use of oral azithromycin as part of the SAFE strategy to eliminate blinding trachoma.

  1. Before the examinations, we will do a census and a sketch map of houses in each village. Particular emphasis will be placed on identifying all the children between 1 and 6 years of age. These children are the chief reservoir of infection, and would have been too young (or unborn) at the ACT study treatment, so it is of particular interest to determine their disease and infection status.
  2. Egyptian ophthalmologists will examine the eyelids, conjunctiva and cornea using magnifying loupes and a hand held light, with grading following the ACT protocol which contains categories referable to the W.H.O. detailed grading scheme. The clinical findings will be recorded on a standardized form.
  3. Egyptian health aides will photograph the inside of the right upper eyelid of all subjects. The photographs of the subjects at the initial visit and all subsequent examinations will be examined to confirm the consistency of clinical findings over the period of the study.
  4. To test for chlamydial infection, a single fiber-tipped swab will be stroked gently over the conjunctiva of the right eye by an Egyptian ophthalmologist. These swabs will be placed in special tubes and tested for Chlamydia trachomatis by a nucleic acid amplification assay. [APTIMA® Gen-Probe Inc. (San Diego, CA.)] The APTIMA® assay detects DNA via r-RNA by a process called transcription mediated amplification. Laboratory testing will be performed at the Chlamydia Research Laboratory at University of California, San Francisco.

  5. After the results are obtained from the nucleic acid amplification testing performed at the laboratory in San Francisco, treatment for trachoma will be done with a single-dose of oral azithromycin (20 mg/kg body weight in children, 1.0 gm adults). The azithromycin will be donated by Pfizer International. Young children will be weighed to determine the dose of azithromycin and the doses administered by a health aide under direct supervision of an Egyptian physician (Dr. Mahfouz). One set of subjects (1 or 2 villages depending upon population size, in order to generate meaningful numbers) will receive an initial treatment of 1.0 gm azithromycin; while the second set of subjects will receive an initial treatment of 1.0 gm azithromycin, followed by a second dose of 1.0 gm azithromycin at 30 days post treatment.

    1. If the prevalence of clinical trachoma is over 20% in children 10 and under, everyone in the village will be treated with oral azithromycin.

      After initial azithromycin treatment, follow-up examinations and specimen collection will be done 2, 12, and 24 months post-treatment for trachoma and chlamydial infection.

    2. If the prevalence is 10% to 20%, all children 10 and under, and the families of those children with active trachoma, will be treated.

      After initial azithromycin treatment, follow-up examinations and specimen collection will be done 2, 12, and 24 months post-treatment for trachoma and chlamydial infection.

    3. If the prevalence is less than 10%, only children with active disease and their families will receive treatment. There will be no follow-up examinations.

    Adults and older children will be told that azithromycin can cause nausea, vomiting, or loose stools or vomiting in some children and adults, and can occur in up to 5% (1 person in 20) of those treated.

    It should be noted that in our previous ACT study, more than 8,000 people received azithromycin with no complaints beyond minor gastro-intestinal upset.

  6. All positive specimens will have the major outer membrane gene amplified and sequenced. The genovars will be mapped for location within villages and families and then their distribution will be followed over time, after treatment to provide a better understanding of the epidemiology of the infection. Results of the study will be used as data input for the generation of mathematical models to predict whether community-wide retreatment (or alternate strategies) will be needed, and the optimal timing for such retreatment.

Study Type

Interventional

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • San Francisco, California, United States, 94143
        • University of California, San Francisco

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Person resides within a selected rural village in a trachoma-endemic area of Egypt.

Exclusion Criteria:

  • Person does not reside in one of the three rural villages being studied.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm 1
Subjects residing in villages assigned to treatment arm 1 will receive a clinical evaluation for trachoma and provide a swab specimen of conjunctivae of the R eye at enrollment (Day 0); will be treated with Azithromycin at Day 30; will be re-screened (clinical evaluation and swab specimen of R eye collected) at Day 60; and again at Day 360.
Drug: Azithromycin
1 gm Azithromycin orally, provided as four 250 mg tablets for adults; pediatric suspension will be provided to children > 1 year old (20 mg/kg body weight) to a maximal dose of 500 mg. One dose vs 2 doses given 30 days apart.
Other Names:
  • Zithromax
  • Zmax
Experimental: Arm 2
Subjects residing in villages assigned to treatment arm 2 will receive a clinical evaluation for trachoma and provide a swab specimen of conjunctivae of the R eye at enrollment (Day 0), as well as receive an initial treatment with Azithromycin; will receive a second dose of Azithromycin at Day 30; will be re-screened (clinical evaluation and swab specimen of R eye collected) at Day 60; and again at Day 360.
Drug: Azithromycin
1 gm Azithromycin orally, provided as four 250 mg tablets for adults; pediatric suspension will be provided to children > 1 year old (20 mg/kg body weight) to a maximal dose of 500 mg. One dose vs 2 doses given 30 days apart.
Other Names:
  • Zithromax
  • Zmax

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Infection with Chlamydia trachomatis diagnosed by use of NAAT
Time Frame: One-year
One-year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of California, San Francisco

Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

  • Principal Investigator: Chandler R Dawson, MD, University of California, San Francisco

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2005

Primary Completion (Actual)

August 1, 2007

Study Completion (Actual)

August 1, 2009

Study Registration Dates

First Submitted

January 31, 2006

First Submitted That Met QC Criteria

January 31, 2006

First Posted (Estimate)

February 2, 2006

Study Record Updates

Last Update Posted (Estimate)

April 16, 2012

Last Update Submitted That Met QC Criteria

April 12, 2012

Last Verified

April 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • H1079-17254
  • 5R01AI048789 (U.S. NIH Grant/Contract)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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