Six-months Versus Nine-months ATT for Ocular TB

September 23, 2024 updated by: HERF, L.V. Prasad Eye Institute

Prospective Randomised Trial for 6-Months Versus 9-Months Anti-TB Therapy for Tubercular Posterior Uveitis

The goal of this clinical trial is to learn if 6-months anti-TB therapy is not worse than 9-months therapy for the treatment of tubercular posterior uveitis. The main questions it aims to answer are:

Does six-month therapy work as well as the nine-month therapy? Do any of the specific phenotypes of TB posterior uveitis respond better to any specific duration of anti-TB therapy?

Participants:

Took the standard dose of six- or nine-month ATT for TB posterior uveitis Visit the clinic as advised for checkups and tests

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

  1. Tubercular uveitis (TBU) is a major cause of intraocular inflammation in TB-endemic countries. It has several clinical manifestations affecting nearly every tissue in the eye. Histopathological studies of TBU have revealed presence of paucibacillary mycobacterial infection and granulomatous infection in enucleated eyes. Unlike TB in other organ systems, microbiological evidence of TB is rarely found in ocular fluids that are sampled from TBU eyes. Hence, the diagnosis of TBU is based on presence of characteristic clinical signs, ancillary evidence of systemic TB infection and exclusion of non-TB entities. Active pulmonary TB, however, is rarely found in TBU patients.
  2. While there are no agreed management guidelines for TBU, several studies, both from TB-endemic and non-endemic countries, have supported the utility of anti-TB therapy (ATT) in the resolution of ocular inflammation, and prevention of recurrence. Delay in initiation of ATT has led to chronic inflammation and prolonged visual impairment in TBU [6]. These studies have typically been retrospective and have included patients with wide range of clinical presentations, based on diagnostic criteria, described above. Majority of these studies have used adjunctive corticosteroids and/or immunosuppressants along with ATT. The duration of ATT in these studies have varied from 6-24 months. A meta-analysis of these studies revealed that 84% (95% CI 79-89) of the patients receiving ATT had no recurrence of inflammation during the follow-up period.

AIM of the study: To compare the efficacy of 6-month with that of 9-month ATT, for the treatment of clinically diagnosed tubercular posterior uveitis (TPU).

Study design: An international, multicenter, prospective, randomized, observer masked-study in three centres spread across India, Myanmar and Thailand.

Patient assesment: This included detailed history of ocular and systemic illnesses, history of TB contact in past, ETDRS best corrected visual acuity (converted from Snellens, if ETDRS unavailable), intraocular pressure by Goldmann applanation tonometry, slit lamp biomicroscopy, and indirect ophthalmoscopy. Fundus photography (seven-field or wide-field, if available) was performed for all patients. Other ocular imaging such as fluorescien angiography, fundus autofluorescence, optical coherence tomography (OCT), OCT-angiography or indocyanine green angiography, were performed as per specific requirements in individual cases. All patients with clinical signs compatible with TPU, were investigated for complete blood counts, erythrocyte sedimentation rate, HIV, VDRL, TST and contrast enhanced computed tomography (CECT) of thorax. If CECT is not available at a centre, then a digital X-ray of the chest was considered in lieu of it. IGRA was performed in conjunction with TST, or in patients with strong suspicion of TPU but negative TST. Additional investigations were performed at the discretion of the investigator to rule out non-TB diagnosis.

Follow-up evaluation were done at 2 weeks, 1 month (+/-1 week), 2 months (+/-2 weeks), 4 months (+/-2 weeks), 6 months (+/-4 weeks), 9 months (+/-4weeks), and then 3 monthly (+/-4 weeks), till one year after completion of ATT. The one-year cut-off limit has been chosen, since most recurrences have been known to occur within one year after the completion of ATT (at least in case of pulmonary TB). Ocular and systemic evaluation, including ocular imaging (as described above), will be performed for each visit.

Study Type

Interventional

Enrollment (Actual)

58

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

  • India
    • Odisha
      • Bhubaneswar, Odisha, India, 751034
        • LV Prasad Eye Institute
  • Myanmar
      • Nay Pyi Taw, Myanmar
        • University of Medicine Magway, EENT Hospital
  • Thailand
      • Bangkok, Thailand
        • Ramathibodi Hospital, Mahidol University

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

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Objective evidence of active intraocular inflammation compatible with TPU e.g. active retinal vasculitis (with FA leakage) or choroidal lesions
  • Positive results of tuberculin skin test (TST >=10 mm induration after 48 hours with 5TU) and/or interferon gamma release assay (Quantiferon TB Gold or T-SPOT)
  • May have evidence of healed pulmonary or other TB (but not requiring ATT for that disease)
  • Age more than 18 years, not pregnant

Exclusion Criteria:

  • Ophthalmic findings or ancillary test results consistent with non-TB diagnosis
  • Objective findings showing only non-active disease eg. occluded retinal vessels only, with no FA leakage from non-occluded vessels, or atrophic/scarred choroidal lesions
  • Optic nerve involvement
  • Past history of uveitis
  • Previous ATT for ocular or other disease
  • Concurrent active pulmonary or other TB disease requiring ATT for that disease.
  • HIV infection and other immunocompromised patients
  • Treated with systemic or local corticosteroids within 3 months prior to entry
  • Received anti-VEGF injections within 3 months prior to entry
  • Age <18 years
  • Pregnancy
  • Liver disease
  • Likelihood of poor compliance/ refusal to participate in study

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: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Six months
Six months anti-TB therapy
Drug: Anti-Tuberculosis Treatment
Standard, weight adjusted anti-TB therapy for six months
Drug: Anti-Tuberculosis Treatment
Standard, weight-adjusted anti-TB therapy for nine months
Active Comparator: Nine months
Nine months anti-TB therapy
Drug: Anti-Tuberculosis Treatment
Standard, weight adjusted anti-TB therapy for six months
Drug: Anti-Tuberculosis Treatment
Standard, weight-adjusted anti-TB therapy for nine months

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Non-recurrence of inflammation
Time Frame: One year after completion of ATT
Treatment failure after completion of 6- or 9-month ATT.
One year after completion of ATT

Collaborators and Investigators

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

Sponsor

L.V. Prasad Eye Institute

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 (Actual)

January 1, 2020

Primary Completion (Actual)

December 31, 2022

Study Completion (Actual)

June 30, 2023

Study Registration Dates

First Submitted

September 23, 2024

First Submitted That Met QC Criteria

September 23, 2024

First Posted (Actual)

September 26, 2024

Study Record Updates

Last Update Posted (Actual)

September 26, 2024

Last Update Submitted That Met QC Criteria

September 23, 2024

Last Verified

September 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2019-011-BHR-29

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

We will need approval from the respective IRBs of each of the three study sites to share the IPD

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

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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