UnknownPhase 3

TB-IRIS NSAID Cox-2 Inhibitor Prevention Trial

South Africa200 participantsStarted 2014-04

Plain-language summary

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

Who can participate

Age range

18 Years

Sex

ALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

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

Questions worth asking your doctor

Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.

1Based on my diagnosis and history, is this trial worth exploring for me — or is there a standard treatment we should try first?
2What does this trial's phase tell us about how much is already known about its safety and benefit?
3What would taking part actually involve for me — visits, tests, time, and travel?
4What are the known and possible risks or side effects I should weigh, and how would they be monitored?
5If this trial isn't the right fit, what other options or trials would you suggest I look into?

Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.

Questions for the trial coordinator

The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.

1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?

A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.

What they're measuring

Incidence of TB IRIS

Timeframe: 6 months

Trial details

NCT IDNCT02060006

SponsorUniversity of Stellenbosch

Sponsor typeOTHER

Study typeINTERVENTIONAL

Primary completion2015-04

Contact for this trial

Jean B Nachega, MD, PhD

+27 21 938 9933 JNACHEGA@SUN.AC.ZA

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