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

NCT01442428

Last updated date
Study Location
Ramathibodi Hospital
Bangkok, , , Thailand
Contact
1-800-718-1021

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Eligibility Criteria
condition
The disease, disorder, syndrome, illness, or injury that is being studied.
Immune Reconstitution Inflammatory Syndrome, Immune Reconstitution Syndrome, Tuberculosis, HIV-infection/Aids
Sex
Females and Males
Age
Pediatric Trials: 0-17 Years
Adult Trials: 18+ Years
18 + years
Inclusion Criteria
The factors, or reasons, that allow a person to participate in a clinical study.
Show details

- 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
The factors, or reasons, that prevent a person from participating in a clinical study.
Show details


- 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

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Immune Reconstitution Inflammatory Syndrome, Immune Reconstitution Syndrome, Tuberculosis, HIV-infection/AidsParadoxical Tuberculosis Immune Reconstitution Inflammatory Syndrome (TB-IRIS) Treatment Trial
NCT01442428
  1. Bangkok,
  2. Chiang Mai,
  3. Nonthaburi,
ALL GENDERS
18 Years+
years
MULTIPLE SITES
Advanced Information
Descriptive Information
Brief Title  ICMJE Paradoxical Tuberculosis Immune Reconstitution Inflammatory Syndrome (TB-IRIS) Treatment Trial
Official Title  ICMJE Randomized Controlled Trial for Corticosteroids Versus NSAIDs With or Without Adjunctive Atorvastatin for the Treatment for Paradoxical Tuberculosis Immune Reconstitution Inflammatory Syndrome
Brief 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Immune Reconstitution Inflammatory Syndrome
  • Immune Reconstitution Syndrome
  • Tuberculosis
  • HIV-infection/Aids
Intervention  ICMJE
  • Drug: Dexamethasone
    Dexamethasone: 4 mg 3x daily for 2 weeks, then 2x daily for 1 week, then once daily for 1 week
    Other Name: decadron
  • Drug: Atorvastatin
    Atorvastatin: 80 mg once daily (equivalent to 30mg ± 10mg with rifamycin co-administration in this TB population)
    Other Name: Lipitor
  • Drug: Naproxen
    Naproxen: 250 mg 3x daily for 2 weeks, then 2x daily for 1 week, then once daily for 1 week
    Other Names:
    • naproxen sodium
    • Aleve
    • Anaprox
    • Antalgin
    • Feminax Ultra
    • Flanax
    • Inza
    • Midol Extended Relief
    • Nalgesin
    • Naposin
    • Naprelan
    • Naprogesic
    • Naprosyn
    • Narocin
    • Proxen
    • Synflex
    • Xenobid
  • Drug: Placebo
    Atorvastatin placebo
Study Arms  ICMJE
  • Experimental: 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)
    Interventions:
    • Drug: Dexamethasone
    • Drug: Atorvastatin
  • Active Comparator: 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)
    Interventions:
    • Drug: Atorvastatin
    • Drug: Naproxen
  • Active Comparator: 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
    Interventions:
    • Drug: Dexamethasone
    • Drug: Placebo
  • Active Comparator: 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
    Interventions:
    • Drug: Naproxen
    • Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Withdrawn
Actual Enrollment  ICMJE
 (submitted: November 20, 2013)
0
Original Estimated Enrollment  ICMJE
 (submitted: September 27, 2011)
100
Estimated Study Completion Date  ICMJE June 2016
Estimated Primary Completion Date March 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study:All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Thailand
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01442428
Other Study ID Numbers  ICMJE WS967180
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University of Minnesota
Study Sponsor  ICMJE University of Minnesota
Collaborators  ICMJE
  • Pfizer
  • Minnesota Medical Foundation
Investigators  ICMJE
Principal Investigator:Sasisopin Kiertiburanakul, MD, MHSMahidol University
Study Chair:David R Boulware, MD, MPHUniversity of Minnesota
Study Director:Ubonvan Jongwutiwes, MDMemorial Sloan Kettering Cancer Center
PRS Account University of Minnesota
Verification Date November 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP