Azithromycin in Control of Trachoma II

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Brief Title

Azithromycin in Control of Trachoma II

Official Title

Azithromycin in Control of Trachoma II

Brief Summary

      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
    

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 Phase

Phase 4

Study Type

Interventional


Primary Outcome

Infection with Chlamydia trachomatis diagnosed by use of NAAT


Condition

Trachoma

Intervention

Azithromycin

Study Arms / Comparison Groups

 Arm 1
Description:  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.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

0

Start Date

June 2005

Completion Date

August 2009

Primary Completion Date

August 2007

Eligibility Criteria

        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.
      

Gender

All

Ages

N/A - N/A

Accepts Healthy Volunteers

Accepts Healthy Volunteers

Contacts

Julius Schachter, PhD, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT00286026

Organization ID

H1079-17254

Secondary IDs

5R01AI048789

Responsible Party

Principal Investigator

Study Sponsor

University of California, San Francisco

Collaborators

 National Institute of Allergy and Infectious Diseases (NIAID)

Study Sponsor

Julius Schachter, PhD, Principal Investigator, University of California, San Francisco


Verification Date

April 2012