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

NCT ID: NCT01442428

Last Updated: 2013-11-25

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

WITHDRAWN

Clinical Phase

PHASE2/PHASE3

Study Classification

INTERVENTIONAL

Study Start Date

2014-01-31

Study Completion Date

2016-06-30

Brief Summary

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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.

Detailed Description

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Conditions

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

Keywords

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TB AIDS HIV IRIS immune reconstitution inflammatory syndrome anti-inflammatory treatment

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

FACTORIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Steroid+Statin

1. Dexamethasone: 4 mg 3x daily for 2 weeks, then 2x daily for 1 week, then once daily for 1 week;
2. Atorvastatin: 80 mg once daily (equivalent to 30mg ± 10mg with rifamycin co-administration)

Group Type EXPERIMENTAL

Dexamethasone

Intervention Type DRUG

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

Atorvastatin

Intervention Type DRUG

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

NSAID+Statin

1. Naproxen: 250 mg 3x daily for 2 weeks, then 2x daily for 1 week, then once daily for 1 week;
2. Atorvastatin: 80 mg once daily (equivalent to 30mg ± 10mg with rifamycin co-administration)

Group Type ACTIVE_COMPARATOR

Atorvastatin

Intervention Type DRUG

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

Naproxen

Intervention Type DRUG

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

Steroid+Placebo

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

Group Type ACTIVE_COMPARATOR

Dexamethasone

Intervention Type DRUG

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

Placebo

Intervention Type DRUG

Atorvastatin placebo

NSAID+Placebo

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

Group Type ACTIVE_COMPARATOR

Naproxen

Intervention Type DRUG

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

Placebo

Intervention Type DRUG

Atorvastatin placebo

Interventions

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Dexamethasone

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

Intervention Type DRUG

Atorvastatin

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

Intervention Type DRUG

Naproxen

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

Intervention Type DRUG

Placebo

Atorvastatin placebo

Intervention Type DRUG

Other Intervention Names

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decadron Lipitor naproxen sodium Aleve Anaprox Antalgin Feminax Ultra Flanax Inza Midol Extended Relief Nalgesin Naposin Naprelan Naprogesic Naprosyn Narocin Proxen Synflex Xenobid

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Pfizer

INDUSTRY

Sponsor Role collaborator

Minnesota Medical Foundation

OTHER

Sponsor Role collaborator

University of Minnesota

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Sasisopin Kiertiburanakul, MD, MHS

Role: PRINCIPAL_INVESTIGATOR

Mahidol University

David R Boulware, MD, MPH

Role: STUDY_CHAIR

University of Minnesota

Ubonvan Jongwutiwes, MD

Role: STUDY_DIRECTOR

Memorial Sloan Kettering Cancer Center

Locations

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Ramathibodi Hospital

Bangkok, , Thailand

Site Status

Chiang Mai University

Chiang Mai, , Thailand

Site Status

Bamrasnaradura Infectious Diseases Institute

Nonthaburi, , Thailand

Site Status

Countries

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Thailand

Other Identifiers

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WS967180

Identifier Type: -

Identifier Source: org_study_id