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

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.

Conditions

• Immune Reconstitution Inflammatory Syndrome
• Immune Reconstitution Syndrome
• Tuberculosis
• HIV-infection/Aids

Interventions

DRUG

Dexamethasone

Dexamethasone: 4 mg 3x daily for 2 weeks, then 2x daily for 1 week, then once daily for 1 week

DRUG

Atorvastatin

Atorvastatin: 80 mg once daily (equivalent to 30mg ± 10mg with rifamycin co-administration in this TB population)

DRUG

Naproxen

Naproxen: 250 mg 3x daily for 2 weeks, then 2x daily for 1 week, then once daily for 1 week

DRUG

Placebo

Atorvastatin placebo

Sponsors & Collaborators

• Pfizer

  collaborator INDUSTRY

• Minnesota Medical Foundation

  collaborator OTHER

• University of Minnesota

  lead OTHER

Principal Investigators

• Sasisopin Kiertiburanakul, MD, MHS · Mahidol University

• David R Boulware, MD, MPH · University of Minnesota

• Ubonvan Jongwutiwes, MD · Memorial Sloan Kettering Cancer Center

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

FACTORIAL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2014-01-31

Primary Completion

2016-03-31

Completion

2016-06-30

Countries

• Thailand

Study Locations