Immune Reconstitution Inflammatory SyndromePhase 2/3NCT01442428
Paradoxical Tuberculosis Immune Reconstitution Inflammatory Syndrome (TB-IRIS) Treatment Trial
A Phase 2/3 study testing Dexamethasone, Atorvastatin and Naproxen in people with Immune Reconstitution Inflammatory Syndrome and Immune Reconstitution Syndrome, run by University of Minnesota at 3 sites in Thailand.
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Immune Reconstitution Inflammatory Syndrome, Immune Reconstitution Syndrome, Tuberculosis
- What is being tested?
- Dexamethasone, Atorvastatin and Naproxen
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 3 sitesThailand
- Study dates
- Jan 2014to Jun 2016
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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;
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- 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.
- 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
Trial locations and contacts
3 sites in 1 country.
Thailand3 sites
Ramathibodi Hospital
Bangkok
Chiang Mai University
Chiang Mai
Bamrasnaradura Infectious Diseases Institute
Nonthaburi
About this study
Official title: Randomized Controlled Trial for Corticosteroids Versus NSAIDs With or Without Adjunctive Atorvastatin for the Treatment for Paradoxical Tuberculosis Immune Reconstitution Inflammatory Syndrome
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.
- Conditions
- Immune Reconstitution Inflammatory Syndrome, Immune Reconstitution Syndrome, Tuberculosis, HIV-infection/Aids
- Being tested
- Dexamethasone, Atorvastatin, Naproxen, Placebo
- Keywords
- TB, AIDS, HIV, IRIS, immune reconstitution inflammatory syndrome, anti-inflammatory, treatment
- Medical subject headings
- Immune Reconstitution Inflammatory Syndrome, Tuberculosis, Acquired Immunodeficiency Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DexamethasoneDrug
Also called decadron
Dexamethasone: 4 mg 3x daily for 2 weeks, then 2x daily for 1 week, then once daily for 1 week
AtorvastatinDrug
Also called Lipitor
Atorvastatin: 80 mg once daily (equivalent to 30mg ± 10mg with rifamycin co-administration in this TB population)
NaproxenDrug
Also called naproxen sodium, Aleve, Anaprox, Antalgin
Naproxen: 250 mg 3x daily for 2 weeks, then 2x daily for 1 week, then once daily for 1 week
PlaceboDrug
Atorvastatin placebo
| Study group | Role | What they receive |
|---|---|---|
| Steroid+Statin | Experimental | 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) Receives: Drug: Dexamethasone; Drug: Atorvastatin |
| NSAID+Statin | Active comparator | 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) Receives: Drug: Atorvastatin; Drug: Naproxen |
| Steroid+Placebo | Active comparator | 1. Dexamethasone: 4 mg 3x daily for 2 weeks, then 2x daily for 1 week, then once daily for 1 week;
2. Placebo Receives: Drug: Dexamethasone; Drug: Placebo |
| NSAID+Placebo | Active comparator | 1. Naproxen: 250 mg 3x daily for 2 weeks, then 2x daily for 1 week, then once daily for 1 week;
2. Placebo Receives: Drug: Naproxen; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Clinical Symptom Score at Day 7, as measured by the 10-point visual analog scale to quantify symptom severity.
Measured: Day 7
Change in serum C-reactive protein at Day 7
Measured: Day 7
Secondary outcomes (10)
Days of hospitalization combined with outpatient therapeutic procedures
Measured: 56 days
Study medicine discontinuation
(e.g. switching to open-label medication)
Measured: 28 days
Karnofsky Performance Status Scale at day 7 and 28;
Measured: Day 7 and Day 28
Incidence of Adverse Events
DAIDS Grading Scale 3-5 events
Measured: 56 days
Radiologic improvement at 2 weeks;
Measured: 14 days
Mortality
Measured: 56 days
CD4 count change
Measured: 28 days
Recurrence of IRIS manifestations within the 8 week study period
Measured: 56 days
ART or TB therapy discontinuation
Measured: 56 days
Incidence of sputum acid fast bacilli (AFB) smear positivity at day 28
Measured: Day 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Sep 2011 (estimated)
- Study startJan 2014
- Primary completionMar 2016 (estimated)
- Study completionJun 2016 (estimated)
Why it stopped: 2011 Thailand flooding led to loss of GMP pharmacy, project delays, and further regulatory challenges.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Immune Reconstitution Inflammatory SyndromeStudies of the same condition, open and under way.
- More trials run by University of MinnesotaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Minnesota
- Sponsor type
- University, hospital or other
- Collaborators
- Pfizer, Minnesota Medical Foundation
- Responsible party
- Sponsor
- Investigators
- Sasisopin Kiertiburanakul, MD, MHS, Principal investigator, Mahidol UniversityDavid R Boulware, MD, MPH, Study chair, University of MinnesotaUbonvan Jongwutiwes, MD, Study director, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01442428
- Sponsor's protocol ID
- WS967180
- Status last verified
- Nov 2013
- First submitted
- 30 Aug 2011
- Last updated
- 25 Nov 2013
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 25 Nov 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Controlled Trial for Corticosteroids Versus NSAIDs With or Without Adjunctive Atorvastatin for the Treatment for Paradoxical Tuberculosis Immune Reconstitution Inflammatory Syndrome
- ClinicalTrials.gov ID
- NCT01442428
- Acronym / sponsor ID
- WS967180
- Conditions
- Immune Reconstitution Inflammatory Syndrome, Immune Reconstitution Syndrome, Tuberculosis, HIV-infection/Aids
- Keywords
- TB, AIDS, HIV, IRIS, immune reconstitution inflammatory syndrome, anti-inflammatory, treatment
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: 2011 Thailand flooding led to loss of GMP pharmacy, project delays, and further regulatory challenges.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of MinnesotaUniversity, hospital or other
- Collaborators
- Pfizer, Minnesota Medical Foundation
- Study start
- Jan 2014
- Primary completion
- Mar 2016 (estimated)
- Study completion
- Jun 2016 (estimated)
- First posted
- 28 Sep 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Steroid+Statin | Experimental | Drug: Dexamethasone, Drug: Atorvastatin1. 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) |
| NSAID+Statin | Active comparator | Drug: Atorvastatin, Drug: Naproxen1. 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) |
| Steroid+Placebo | Active comparator | Drug: Dexamethasone, Drug: Placebo1. Dexamethasone: 4 mg 3x daily for 2 weeks, then 2x daily for 1 week, then once daily for 1 week; 2. Placebo |
| NSAID+Placebo | Active comparator | Drug: Naproxen, Drug: Placebo1. Naproxen: 250 mg 3x daily for 2 weeks, then 2x daily for 1 week, then once daily for 1 week; 2. Placebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (25 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DexamethasoneAlso: decadronDexamethasone: 4 mg 3x daily for 2 weeks, then 2x daily for 1 week, then once daily for 1 week | Drug | Steroid+Placebo, Steroid+Statin |
| AtorvastatinAlso: LipitorAtorvastatin: 80 mg once daily (equivalent to 30mg ± 10mg with rifamycin co-administration in this TB population) | Drug | NSAID+Statin, Steroid+Statin |
| NaproxenAlso: naproxen sodium, Aleve, Anaprox, AntalginNaproxen: 250 mg 3x daily for 2 weeks, then 2x daily for 1 week, then once daily for 1 week | Drug | NSAID+Placebo, NSAID+Statin |
| PlaceboAtorvastatin placebo | Drug | NSAID+Placebo, Steroid+Placebo |
Primary outcome
Change in Clinical Symptom Score at Day 7, as measured by the 10-point visual analog scale to quantify symptom severity.
Time frame: Day 7
Change in serum C-reactive protein at Day 7
Time frame: Day 7
10 secondary outcomes
Days of hospitalization combined with outpatient therapeutic procedures
Time frame: 56 days
Study medicine discontinuation
Time frame: 28 days
Karnofsky Performance Status Scale at day 7 and 28;
Time frame: Day 7 and Day 28
Incidence of Adverse Events
Time frame: 56 days
Radiologic improvement at 2 weeks;
Time frame: 14 days
Mortality
Time frame: 56 days
CD4 count change
Time frame: 28 days
Recurrence of IRIS manifestations within the 8 week study period
Time frame: 56 days
ART or TB therapy discontinuation
Time frame: 56 days
Incidence of sputum acid fast bacilli (AFB) smear positivity at day 28
Time frame: Day 28
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Nov 2013.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sasisopin Kiertiburanakul, MD, MHS principal investigator
Mahidol University
David R Boulware, MD, MPH study chair
University of Minnesota
Ubonvan Jongwutiwes, MD study director
Memorial Sloan Kettering Cancer Center
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Dexamethasone, Atorvastatin and Naproxen in people with Immune Reconstitution Inflammatory Syndrome and Immune Reconstitution Syndrome, run by University of Minnesota at 3 sites in Thailand.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 25 Nov 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Thailand. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Clinical Symptom Score at Day 7, as measured by the 10-point visual analog scale to quantify symptom severity. (time frame: Day 7). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Nov 2013.