TB-IRIS NSAID Cox-2 Inhibitor Prevention Trial

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by University of Stellenbosch
Sponsor:
Collaborator:
University of Pittsburgh
Information provided by (Responsible Party):
Prof Jean Nachega, University of Stellenbosch
ClinicalTrials.gov Identifier:
NCT02060006
First received: February 7, 2014
Last updated: April 2, 2014
Last verified: April 2014
  Purpose

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


Condition Intervention Phase
Tuberculosis
Drug: Meloxicam 7.5mg daily for 8 weeks
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: 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

Resource links provided by NLM:


Further study details as provided by University of Stellenbosch:

Primary Outcome Measures:
  • Incidence of TB IRIS [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Proportion discontinuing Meloxicam due to adverse event [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Estimated Enrollment: 200
Study Start Date: April 2014
Estimated Study Completion Date: April 2015
Estimated Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Drug: Meloxicam 7.5mg daily for 8 weeks
Meloxicam 7.5mg daily for 8 weeks
Other Name: Cox-2 Inhibitor

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02060006

Contacts
Contact: Jean B Nachega, MD, PhD +27 21 938 9933 JNACHEGA@SUN.AC.ZA

Locations
South Africa
Stellenbosch University Tygerberg Hospital Recruiting
Cape Town, Western Cape Province, South Africa, 7505
Contact: Jean B Nachega, MD, PhD    +27219389933    JNACHEGA@SUN.AC.ZA   
Principal Investigator: Jean B Nachega, MD, PhD         
Sponsors and Collaborators
University of Stellenbosch
University of Pittsburgh
  More Information

Publications:

Responsible Party: Prof Jean Nachega, Professor Extraordinary, University of Stellenbosch
ClinicalTrials.gov Identifier: NCT02060006     History of Changes
Other Study ID Numbers: PRO13060453
Study First Received: February 7, 2014
Last Updated: April 2, 2014
Health Authority: South Africa: Medicines Control Council

Keywords provided by University of Stellenbosch:
TB
IRIS

Additional relevant MeSH terms:
Tuberculosis
Immune Reconstitution Inflammatory Syndrome
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Immune System Diseases
Meloxicam
Cyclooxygenase 2 Inhibitors
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Central Nervous System Agents

ClinicalTrials.gov processed this record on September 18, 2014