Preventing TB-IRIS in High-risk Patients: a Randomized Placebo-controlled Trial of Prednisone

• Status: Completed
• Trial end date: 2017-04-01
• Target enrollment: 0
• Participant gender: All

Summary

Tuberculosis (TB) is the most common opportunistic infection amongst HIV-infected patients starting antiretroviral therapy (ART) in developing countries and thus the most frequent form of immune reconstitution inflammatory syndrome (IRIS). Paradoxical TB-IRIS occurs in 8- 43% of patients starting ART while on TB treatment and results in morbidity, hospitalisation, consumes health care resources and TB-IRIS may be fatal. We have previously demonstrated in a clinical trial that prednisone reduces morbidity when used for treatment of paradoxical TB-IRIS. This trial is a double-blind placebo-controlled trial of prophylactic prednisone (40mg/day for 2 weeks followed by 20mg/day for 2 weeks, started on the same day as ART) in patients with TB who are identified as being at high risk for paradoxical TB-IRIS (starting ART within 30 days of initiating TB treatment and CD4 < 100/μL). The trial will enroll 240 participants, randomised 1:1 (prednisone:placebo). The primary endpoint is development of paradoxical TB-IRIS, defined using international consensus case definitions. Secondary endpoints include time to IRIS event, severity of IRIS, quality of life assessment, mortality and corticosteroids adverse events. The trial is powered to determine a reduction in TB-IRIS events.

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

Details

• Lead Sponsor: University of Cape Town
• Collaborators: Department of Science and Technology, South Africa; European and Developing Countries Clinical Trials Partnership (EDCTP); Imperial College London; Institute of Tropical Medicine, Belgium
• Treatments: Prednisone

Criteria

Inclusion Criteria:

1. HIV-infected HIV infection will be confirmed by two different rapid tests (as per South African national Department of Health guidelines) and an HIV viral load test.

2. CD4 count < 100/μL One CD4 count taken within 3 months prior to enrolment less than 100/μL will qualify, even if other CD4 counts are greater than 100/μL

3. ART-naïve Patients who report having been treated with triple drug or dual drug ART previously will be excluded. Single dose nevirapine or short term AZT monotherapy for PMTCT is not an exclusion.

4. Confirmed diagnosis of TB (smear, culture, Xpert MTB/RIF test or compatible histology) or strong clinical and radiological evidence of TB with symptomatic response to TB treatment

5. On TB treatment for less than 30 days prior to study entry.

6. Eligible for ART and patient consents to starting ART within 30 days of starting TB treatment.

7. Written informed consent for trial

Exclusion Criteria:

1. Kaposi's sarcoma (KS) A thorough examination for KS lesions will be performed and any suspicious lesion will be biopsied. Any history of treatment for KS will also be an exclusion.

2. Pregnant All female participants of child-bearing potential will have a pregnancy test performed prior to enrollment and will be counseled to use to two reliable methods of contraception for the duration of the trial.

3. <18 years old

4. TB meningitis or tuberculoma at TB diagnosis

5. Clinical syndrome of pericardial TB at TB diagnosis (a pericardial effusion noted on ultrasound scan alone is not an exclusion criterion)

6. Rifampicin-resistant TB diagnosed by Xpert MTB/RIF test or a drug susceptibility test performed on a culture isolate.

7. On corticosteroids for another indication or on any other immunosuppressive medication within the past 7 days.

8. Uncontrolled diabetes mellitus

9. The following abnormal laboratory values:

Alanine aminotransferase > 200 IU/l Absolute neutrophil count < 500/mm3

10. Not on standard intensive phase TB treatment (Rifampicin, isoniazid, pyrazinamide and ethambutol)

11. Poor clinical response to TB treatment prior to ART as judged by the clinical investigators.

12. Hepatitis B surface antigen positive