TB-IRIS NSAID Cox-2 Inhibitor Prevention Trial

April 2, 2014 updated by: Prof Jean Nachega, University of Stellenbosch

A Double-Blind Randomized Placebo Controlled Trial for Prevention of Tuberculosis-Immune Reconstitution Inflammatory Syndrome With Non-Steroid Anti-Inflammatory Drugs (NSAIDs) in HIV-Infected Adults

Background: Non-Steroid Anti-Inflammatory Drugs (NSAIDs) reduce pain and inflammation by inhibiting cyclooxygenase, an enzyme in the pathway for formation of prostaglandins and thromboxane. Prior studies have proven the role of ibuprofen (an NSAID) in modulating lung injury and decreasing pulmonary damage in cystic fibrosis. While there has been an intense effort by the scientific community to define the best treatment strategies for tuberculosis immune reconstitution inflammatory syndrome (TB-IRIS), to our knowledge there is no available study evaluating preventive strategies using anti-inflammatory agents for TB-IRIS, a highly morbid complication in HIV-infected TB patients initiating antiretroviral therapy (ART).

Design and Methods: We propose to conduct a single center double-blind placebo-controlled randomized trial to investigate the efficacy of daily self-administered Meloxicam (a NSAID) versus placebo for prevention of Tuberculosis associated Immune Reconstitution Inflammatory Syndrome (TB-IRIS). A total of 150 HIV-infected adults who are treated for Tuberculosis for at least 2 weeks and about to initiate HIV treatment at Brewelskloof Hospital, Worcester, and Tygerberg Teaching Hospital, Cape Town, will be randomized to one of the following treatments: Meloxicam 7.5 mg tablet once-a-day, the experimental arm, versus Placebo tablet once-a-day, the control arm, for 8 weeks. All patients will be followed up for 12 months. Primary efficacy outcome: The decrease of the incidence of paradoxical TB IRIS by at least 20%; Primary safety outcome: The proportion of patients who temporarily or permanently discontinue Meloxicam due to any adverse event (e.g. dyspepsia or gastro-intestinal upset). Secondary outcomes are: 1) the proportion of patients in each arm with the following indicators of TB-IRIS severity/quality of life (QOL) (degree of pain or discomfort >III, presence of local or disseminated suppuration/abscess of any site, unscheduled clinic visits, hospitalizations, missed more than a day at work, etc; 2) The incidence of other types of IRIS (e.g. Kaposi Sarcoma or cryptococcal meningitis).

This study will provide important and novel data on the feasibility and efficacy of using a cheap, widely available NSAID used in both developed and developing countries, as a preventive intervention for TB-IRIS that could be quickly put into practice if proven to be effective

Study Overview

Status

Unknown

Conditions

Study Type

Interventional

Enrollment (Anticipated)

200

Phase

  • Phase 3

Contacts and Locations

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

Study Contact

Study Locations

    • Western Cape Province
      • Cape Town, Western Cape Province, South Africa, 7505
        • Recruiting
        • Stellenbosch University Tygerberg Hospital
        • Contact:
        • Principal Investigator:
          • Jean B Nachega, MD, PhD

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

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Males and non-pregnant females age 18 years of age or older
  • Evidence of HIV-1 infection
  • TB treatment (<2 weeks) and initiating EFV-based antiretroviral therapy as per the South African Department of Health Guidelines
  • Living in the study site catchment area and having had a known address for more than 3 months
  • Written informed consent

Exclusion Criteria:

  • History of aspirin sensitivity and allergies to other NSAIDs
  • Current or recent use (<3 months) of aspirin, NSAIDs, or anticoagulants such as warfarin.
  • Current or recent use of corticosteroid therapy
  • History of gastro-intestinal bleeding or peptic ulcer
  • History of cardiovascular thrombotic events (myocardial infarction or stroke), hypertension, or congestive heart failure
  • Severe renal impairment as evidenced by creatinine clearance <50 (Cockcroft- Gault Formula)
  • Severe liver disease (ALT > five times upper limit of normal)
  • Presence of a medical condition likely to result in death within 6 months from start of ART. These conditions include suspected or CNS lymphoma, PMLE and disseminated visceral Kaposi's sarcoma
  • Cognitive disorder(s) that could impair ability to comply with study requirements, as determined by the study physician
  • Karnofsky performance score <60

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: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo 7.5 mg daily for 8 weeks
Placebo 7.5 mg once-daily First 8 weeks of ART Only Control arm
Experimental: Meloxicam 7.5 mg once-daily
Meloxicam 7.5mg once-daily for 8 weeks
Meloxicam 7.5mg daily for 8 weeks
Other Names:
  • Cox-2 Inhibitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Incidence of TB IRIS
Time Frame: 6 months
6 months

Secondary Outcome Measures

Outcome Measure
Time Frame
Proportion discontinuing Meloxicam due to adverse event
Time Frame: 6 months
6 months
The proportion of patients in each arm with the following indicators of TB-IRIS severity/quality of life (QOL) (degree of pain or discomfort >III
Time Frame: 6 months
6 months
The proportion of patients with local or disseminated suppuration/abscess of any site, unscheduled clinic visits, hospitalizations, missed more than a day at work, etc
Time Frame: 6 months
6 months

Collaborators and Investigators

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

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

April 1, 2014

Primary Completion (Anticipated)

April 1, 2015

Study Completion

April 1, 2015

Study Registration Dates

First Submitted

February 7, 2014

First Submitted That Met QC Criteria

February 7, 2014

First Posted (Estimate)

February 11, 2014

Study Record Updates

Last Update Posted (Estimate)

April 3, 2014

Last Update Submitted That Met QC Criteria

April 2, 2014

Last Verified

April 1, 2014

More Information

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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