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Clinical Trial Details — Status: Withdrawn

Administrative data

NCT number NCT01442428
Other study ID # WS967180
Secondary ID
Status Withdrawn
Phase Phase 2/Phase 3
First received August 30, 2011
Last updated November 20, 2013
Start date January 2014
Est. completion date June 2016

Study information

Verified date November 2013
Source University of Minnesota - Clinical and Translational Science Institute
Contact n/a
Is FDA regulated No
Health authority Thailand: Ethical CommitteeUnited States: Institutional Review Board
Study type Interventional

Clinical 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.


Recruitment information / eligibility

Status Withdrawn
Enrollment 0
Est. completion date June 2016
Est. primary completion date March 2016
Accepts healthy volunteers No
Gender Both
Age group 18 Years and older
Eligibility 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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Factorial Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment


Related Conditions & MeSH terms


Intervention

Drug:
Dexamethasone
Dexamethasone: 4 mg 3x daily for 2 weeks, then 2x daily for 1 week, then once daily for 1 week
Atorvastatin
Atorvastatin: 80 mg once daily (equivalent to 30mg ± 10mg with rifamycin co-administration in this TB population)
Naproxen
Naproxen: 250 mg 3x daily for 2 weeks, then 2x daily for 1 week, then once daily for 1 week
Placebo
Atorvastatin placebo

Locations

Country Name City State
Thailand Ramathibodi Hospital Bangkok
Thailand Chiang Mai University Chiang Mai
Thailand Bamrasnaradura Infectious Diseases Institute Nonthaburi

Sponsors (3)

Lead Sponsor Collaborator
University of Minnesota - Clinical and Translational Science Institute Minnesota Medical Foundation, Pfizer

Country where clinical trial is conducted

Thailand, 

Outcome

Type Measure Description Time frame Safety issue
Primary Change in Clinical Symptom Score at Day 7, as measured by the 10-point visual analog scale to quantify symptom severity. Day 7 No
Primary Change in serum C-reactive protein at Day 7 Day 7 No
Secondary Days of hospitalization combined with outpatient therapeutic procedures 56 days No
Secondary Study medicine discontinuation (e.g. switching to open-label medication) 28 days Yes
Secondary Karnofsky Performance Status Scale at day 7 and 28; Day 7 and Day 28 No
Secondary Incidence of Adverse Events DAIDS Grading Scale 3-5 events 56 days Yes
Secondary Radiologic improvement at 2 weeks; 14 days No
Secondary Mortality 56 days Yes
Secondary CD4 count change 28 days Yes
Secondary Recurrence of IRIS manifestations within the 8 week study period 56 days No
Secondary ART or TB therapy discontinuation 56 days Yes
Secondary Incidence of sputum acid fast bacilli (AFB) smear positivity at day 28 Day 28 Yes
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