Paradoxical Tuberculosis Immune Reconstitution Inflammatory Syndrome (TB-IRIS) Treatment Trial
Keywords
Abstract
Dates
| Last Verified: | 10/31/2013 |
| First Submitted: | 08/29/2011 |
| Estimated Enrollment Submitted: | 09/26/2011 |
| First Posted: | 09/27/2011 |
| Last Update Submitted: | 11/19/2013 |
| Last Update Posted: | 11/24/2013 |
| Actual Study Start Date: | 12/31/2013 |
| Estimated Primary Completion Date: | 02/29/2016 |
| Estimated Study Completion Date: | 05/31/2016 |
Condition or disease
Intervention/treatment
Drug: Dexamethasone
Drug: Atorvastatin
Drug: Naproxen
Drug: Placebo
Phase
Arm Groups
| Arm | Intervention/treatment |
|---|---|
| Experimental: Steroid+Statin Dexamethasone: 4 mg 3x daily for 2 weeks, then 2x daily for 1 week, then once daily for 1 week;
Atorvastatin: 80 mg once daily (equivalent to 30mg ± 10mg with rifamycin co-administration) | |
| Active Comparator: NSAID+Statin Naproxen: 250 mg 3x daily for 2 weeks, then 2x daily for 1 week, then once daily for 1 week;
Atorvastatin: 80 mg once daily (equivalent to 30mg ± 10mg with rifamycin co-administration) | |
| Active Comparator: Steroid+Placebo Dexamethasone: 4 mg 3x daily for 2 weeks, then 2x daily for 1 week, then once daily for 1 week;
Placebo | |
| Active Comparator: NSAID+Placebo Naproxen: 250 mg 3x daily for 2 weeks, then 2x daily for 1 week, then once daily for 1 week;
Placebo |
Eligibility Criteria
| Ages Eligible for Study | 18 Years To 18 Years |
| Sexes Eligible for Study | All |
| Accepts Healthy Volunteers | Yes |
| 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 |
Outcome
Primary Outcome Measures
1. Change in Clinical Symptom Score at Day 7, as measured by the 10-point visual analog scale to quantify symptom severity. [Day 7]
2. Change in serum C-reactive protein at Day 7 [Day 7]
Secondary Outcome Measures
1. Days of hospitalization combined with outpatient therapeutic procedures [56 days]
2. Study medicine discontinuation [28 days]
3. Karnofsky Performance Status Scale at day 7 and 28; [Day 7 and Day 28]
4. Incidence of Adverse Events [56 days]
5. Radiologic improvement at 2 weeks; [14 days]
6. Mortality [56 days]
7. CD4 count change [28 days]
8. Recurrence of IRIS manifestations within the 8 week study period [56 days]
9. ART or TB therapy discontinuation [56 days]
10. Incidence of sputum acid fast bacilli (AFB) smear positivity at day 28 [Day 28]
