Preventing paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome in high-risk patients: protocol of a randomized placebo-controlled trial of prednisone (predART trial)

Cari Stek, Charlotte Schutz, Lisette Blumenthal, Friedrich Thienemann, Jozefien Buyze, Christiana Nöstlinger, Raffaella Ravinetto, Edwin Wouters, Robert Colebunders, Gary Maartens, Robert J Wilkinson, Lutgarde Lynen, Graeme Meintjes

Research output: Contribution to journalA2: International peer reviewed article (not A1-type)

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Abstract

BACKGROUND: Early antiretroviral therapy (ART) initiation in patients diagnosed with HIV-associated tuberculosis (TB) reduces mortality among those with the lowest CD4 counts. At the same time, both early ART and a low CD4 count heighten the risk of paradoxical TB-associated immune reconstitution inflammatory syndrome (TB-IRIS). TB is common in patients starting ART in sub-Saharan Africa. Safe interventions that reduce the incidence or severity of TB-IRIS are needed. Prednisone has been shown to reduce symptoms and markers of inflammation when used to treat TB-IRIS.

OBJECTIVE: To determine whether prophylactic prednisone in patients at high risk for paradoxical TB-IRIS initiating ART reduces the incidence of TB-IRIS.

METHODS: We are conducting a randomized, double-blind, placebo-controlled trial of prophylactic prednisone (40 mg/day for 2 weeks, followed by 20 mg/day for 2 weeks) initiated at the same time as ART in patients at high risk for TB-IRIS (starting ART within 30 days of TB treatment and CD4 count ≤100/μL). The primary endpoint is development of TB-IRIS, defined using an international consensus case definition. Secondary endpoints include time to TB-IRIS event, severity of TB-IRIS, quality of life, mortality, hospitalization, other infections and malignancies, and adverse events including corticosteroid adverse effects.

RESULTS: Enrollment for the trial began in August 2013. All 240 participants have been enrolled, and safety follow-up will be completed in March 2017.

CONCLUSION: No preventive strategies for TB-IRIS currently exist. If results of this trial demonstrate the efficacy and safety of prednisone, this will provide clinicians with an evidence-based preventive strategy in patients at high risk for paradoxical TB-IRIS when initiating ART.

Original languageEnglish
JournalJMIR Research Protocols
Volume5
Issue number3
Pages (from-to)e173
Number of pages13
ISSN1929-0748
DOIs
Publication statusPublished - 2016

Keywords

  • Journal Article

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