Paradoxical Tuberculosis Immune Reconstitution Inflammatory Syndrome (TB-IRIS) Treatment Trial

• Status: Withdrawn
• Trial end date: 2016-06-01
• Target enrollment: 0
• Participant gender: All

Summary

Tuberculosis is the most common opportunistic infection (OI) in HIV-infected persons worldwide, including in South East Asia. Significant numbers of patients experience tuberculosis-related paradoxical immune reconstitution inflammatory syndrome (TB-IRIS) after ART initiation, yet the optimal treatment of TB-IRIS is unknown. A recent randomized-controlled trial showed the benefit of prednisone over placebo in reduction of days of hospitalization and invasive procedures. The investigators hypothesize that nonsteroidal anti-inflammatory drugs (NSAIDs) are as effective as corticosteroids for treatment of non-life threatening TB-IRIS in HIV-infected patients and hypothesize that adjunctive treatment with 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (Statins) may improve the outcomes. This is a randomized controlled trial with a 2x2 factorial design to test the relative benefit of corticosteroids, NSAIDS, and Statins for the symptomatic and immunologic control of TB-IRIS.

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Minnesota; University of Minnesota - Clinical and Translational Science Institute
• Collaborators: Minnesota Medical Foundation; Pfizer
• Treatments: Atorvastatin; Atorvastatin Calcium; BB 1101; Dexamethasone; Dexamethasone 21-phosphate; Dexamethasone acetate; Naproxen; Rifamycins

Criteria

Inclusion Criteria:

• HIV-1 infection documented by any locally licensed ELISA or rapid HIV test kit.

• Age >18 years

• Paradoxical TB-IRIS diagnosed by case definition (see section 5.2)

• Ability and willingness of the participant or legal guardian/representative to give informed consent. Receiving appropriate ART and anti-TB therapy, as judged by the site investigator

Exclusion Criteria:

• Inability to take oral medication;

• Receiving chemotherapy, immunosuppressant, corticosteroid, NSAID, or statin medications; (ASA is acceptable)

• Cannot or unlikely to attend regular clinic visits;

• Known allergy to NSAIDs, statins or corticosteroids;

• Liver transaminase > 2 times the upper limit of normal within 60 days of enrollment;

• History of myositis/myopathy;

• High Investigator Suspicion of anti-TB treatment failure due to TB-resistance or medication non-adherence;

• Receiving ongoing azole anti-fungal for treatment or secondary prophylaxis of cryptococcosis, histoplasmosis or penicilliosis;

• Serious co-morbidities, co-infections, or laboratory values who should not receive NSAIDs, steroid or statins, as judged by the site investigator;

• Minimal IRIS reaction which is unlikely to require treatment, as judged by the site investigator;

• Pregnancy (a negative urine pregnancy test at screening is required for women of childbearing potential) or breast feeding;

• Receiving a HIV treatment regimen containing a protease inhibitor at study entry.

Exclusion for Randomization A Only

• Life threatening TB-IRIS, as defined by:

• Acute respiratory failure; PaO2 < 60 on room air or;

• Altered mental status or;

• New focal neurological deficit or;

• Compression of the vital organs.

• Persons with uncontrolled diabetes mellitus;

• Impair kidney function, glomerular filtration rate <60 ml/min; within 72 hours of consent

• Uncontrolled congestive heart failure

• History of bleeding disorder;

• Platelet count <100,000/µL;

• History of significant gastrointestinal bleeding or ulceration;

• Prior adjunctive corticosteroid therapy for this TB episode for > 48 hr;

• Pregnancy