TuberculosisPhase 3NCT02060006
TB-IRIS NSAID Cox-2 Inhibitor Prevention Trial
A Phase 3 study testing Meloxicam 7.5mg daily for 8 weeks in people with Tuberculosis, run by University of Stellenbosch at 1 site in South Africa.
Trial summary
Background: Non-Steroid Anti-Inflammatory Drugs (NSAIDs) reduce pain and inflammation by inhibiting cyclooxygenase, an enzyme in the pathway for formation of prostaglandins and thromboxane. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Tuberculosis
- What is being tested?
- Meloxicam 7.5mg daily for 8 weeks
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 200 participants
- Where
- 1 siteSouth Africa
- Study dates
- Apr 2014to Apr 2015
- Phase
- Phase 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
- Males and non-pregnant females age 18 years of age or older
- Evidence of HIV-1 infection
- TB treatment (<2 weeks) and initiating EFV-based antiretroviral therapy as per the South African Department of Health Guidelines
- Living in the study site catchment area and having had a known address for more than 3 months
- Written informed consent
Who cannot join
- History of aspirin sensitivity and allergies to other NSAIDs
- Current or recent use (<3 months) of aspirin, NSAIDs, or anticoagulants such as warfarin.
- Current or recent use of corticosteroid therapy
- History of gastro-intestinal bleeding or peptic ulcer
- History of cardiovascular thrombotic events (myocardial infarction or stroke), hypertension, or congestive heart failure
- Severe renal impairment as evidenced by creatinine clearance <50 (Cockcroft- Gault Formula)
Show all 10Show fewer
- Severe liver disease (ALT > five times upper limit of normal)
- Presence of a medical condition likely to result in death within 6 months from start of ART. These conditions include suspected or CNS lymphoma, PMLE and disseminated visceral Kaposi's sarcoma
- Cognitive disorder(s) that could impair ability to comply with study requirements, as determined by the study physician
- Karnofsky performance score <60
Trial locations and contacts
1 site in 1 country.
South Africa1 site, 1 recruiting
- Recruiting
Stellenbosch University Tygerberg Hospital
Cape Town, Western Cape, 7505
Jean B Nachega, MD, PhD, +27219389933, JNACHEGA@SUN.AC.ZA
Jean B Nachega, MD, PhD
About this study
Official title: A Double-Blind Randomized Placebo Controlled Trial for Prevention of Tuberculosis-Immune Reconstitution Inflammatory Syndrome With Non-Steroid Anti-Inflammatory Drugs (NSAIDs) in HIV-Infected Adults
Background: Non-Steroid Anti-Inflammatory Drugs (NSAIDs) reduce pain and inflammation by inhibiting cyclooxygenase, an enzyme in the pathway for formation of prostaglandins and thromboxane. Prior studies have proven the role of ibuprofen (an NSAID) in modulating lung injury and decreasing pulmonary damage in cystic fibrosis. While there has been an intense effort by the scientific community to define the best treatment strategies for tuberculosis immune reconstitution inflammatory syndrome (TB-IRIS), to our knowledge there is no available study evaluating preventive strategies using anti-inflammatory agents for TB-IRIS, a highly morbid complication in HIV-infected TB patients initiating antiretroviral therapy (ART).
Design and Methods: We propose to conduct a single center double-blind placebo-controlled randomized trial to investigate the efficacy of daily self-administered Meloxicam (a NSAID) versus placebo for prevention of Tuberculosis associated Immune Reconstitution Inflammatory Syndrome (TB-IRIS). A total of 150 HIV-infected adults who are treated for Tuberculosis for at least 2 weeks and about to initiate HIV treatment at Brewelskloof Hospital, Worcester, and Tygerberg Teaching Hospital, Cape Town, will be randomized to one of the following treatments: Meloxicam 7.5 mg tablet once-a-day, the experimental arm, versus Placebo tablet once-a-day, the control arm, for 8 weeks. All patients will be followed up for 12 months. Primary efficacy outcome: The decrease of the incidence of paradoxical TB IRIS by at least 20%; Primary safety outcome: The proportion of patients who temporarily or permanently discontinue Meloxicam due to any adverse event (e.g. dyspepsia or gastro-intestinal upset). Secondary outcomes are: 1) the proportion of patients in each arm with the following indicators of TB-IRIS severity/quality of life (QOL) (degree of pain or discomfort >III, presence of local or disseminated suppuration/abscess of any site, unscheduled clinic visits, hospitalizations, missed more than a day at work, etc; 2) The incidence of other types of IRIS (e.g. Kaposi Sarcoma or cryptococcal meningitis).
This study will provide important and novel data on the feasibility and efficacy of using a cheap, widely available NSAID used in both developed and developing countries, as a preventive intervention for TB-IRIS that could be quickly put into practice if proven to be effective
- Conditions
- Tuberculosis
- Being tested
- Meloxicam 7.5mg daily for 8 weeks
- Keywords
- TB, IRIS
- Medical subject headings
- Tuberculosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Meloxicam 7.5mg daily for 8 weeksDrug
Also called Cox-2 Inhibitor
Meloxicam 7.5mg daily for 8 weeks
| Study group | Role | What they receive |
|---|---|---|
| Placebo 7.5 mg daily for 8 weeks | Placebo comparator | Placebo 7.5 mg once-daily First 8 weeks of ART Only Control arm |
| Meloxicam 7.5 mg once-daily | Experimental | Meloxicam 7.5mg once-daily for 8 weeks Receives: Drug: Meloxicam 7.5mg daily for 8 weeks |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of TB IRIS
Measured: 6 months
Secondary outcomes (3)
Proportion discontinuing Meloxicam due to adverse event
Measured: 6 months
The proportion of patients in each arm with the following indicators of TB-IRIS severity/quality of life (QOL) (degree of pain or discomfort >III
Measured: 6 months
The proportion of patients with local or disseminated suppuration/abscess of any site, unscheduled clinic visits, hospitalizations, missed more than a day at work, etc
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Feb 2014 (estimated)
- Study startApr 2014
- Primary completionApr 2015 (estimated)
- Study completionApr 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for TuberculosisStudies of the same condition, open and under way.
- 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 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Stellenbosch
- Sponsor type
- University, hospital or other
- Collaborators
- University of Pittsburgh
- Responsible party
- Principal investigator, Prof Jean Nachega, University of Stellenbosch
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02060006
- Sponsor's protocol ID
- PRO13060453
- Status last verified
- Apr 2014
- First submitted
- 7 Feb 2014
- Last updated
- 3 Apr 2014
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Eshun-Wilson I, Havers F, Nachega JB, Prozesky HW, Taljaard JJ, Zeier MD, Cotton M, Simon G, Soentjens P. Evaluation of paradoxical TB-associated IRIS with the use of standardized case definitions for resource-limited settings. J Int Assoc Physicians AIDS Care (Chic). 2010 Mar-Apr;9(2):104-8. doi: 10.1177/1545109710361537. Epub 2010 Feb 16.
PubMed 20160249Meintjes G, Wilkinson RJ, Morroni C, Pepper DJ, Rebe K, Rangaka MX, Oni T, Maartens G. Randomized placebo-controlled trial of prednisone for paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome. AIDS. 2010 Sep 24;24(15):2381-90. doi: 10.1097/QAD.0b013e32833dfc68.
PubMed 20808204Meintjes G, Lawn SD, Scano F, Maartens G, French MA, Worodria W, Elliott JH, Murdoch D, Wilkinson RJ, Seyler C, John L, van der Loeff MS, Reiss P, Lynen L, Janoff EN, Gilks C, Colebunders R; International Network for the Study of HIV-associated IRIS. Tuberculosis-associated immune reconstitution inflammatory syndrome: case definitions for use in resource-limited settings. Lancet Infect Dis. 2008 Aug;8(8):516-23. doi: 10.1016/S1473-3099(08)70184-1.
PubMed 18652998Abdool Karim SS, Naidoo K, Grobler A, Padayatchi N, Baxter C, Gray A, Gengiah T, Nair G, Bamber S, Singh A, Khan M, Pienaar J, El-Sadr W, Friedland G, Abdool Karim Q. Timing of initiation of antiretroviral drugs during tuberculosis therapy. N Engl J Med. 2010 Feb 25;362(8):697-706. doi: 10.1056/NEJMoa0905848.
PubMed 20181971Blanc FX, Sok T, Laureillard D, Borand L, Rekacewicz C, Nerrienet E, Madec Y, Marcy O, Chan S, Prak N, Kim C, Lak KK, Hak C, Dim B, Sin CI, Sun S, Guillard B, Sar B, Vong S, Fernandez M, Fox L, Delfraissy JF, Goldfeld AE; CAMELIA (ANRS 1295-CIPRA KH001) Study Team. Earlier versus later start of antiretroviral therapy in HIV-infected adults with tuberculosis. N Engl J Med. 2011 Oct 20;365(16):1471-81. doi: 10.1056/NEJMoa1013911.
PubMed 22010913Havlir DV, Kendall MA, Ive P, Kumwenda J, Swindells S, Qasba SS, Luetkemeyer AF, Hogg E, Rooney JF, Wu X, Hosseinipour MC, Lalloo U, Veloso VG, Some FF, Kumarasamy N, Padayatchi N, Santos BR, Reid S, Hakim J, Mohapi L, Mugyenyi P, Sanchez J, Lama JR, Pape JW, Sanchez A, Asmelash A, Moko E, Sawe F, Andersen J, Sanne I; AIDS Clinical Trials Group Study A5221. Timing of antiretroviral therapy for HIV-1 infection and tuberculosis. N Engl J Med. 2011 Oct 20;365(16):1482-91. doi: 10.1056/NEJMoa1013607.
PubMed 22010914Konstan MW, Schluchter MD, Xue W, Davis PB. Clinical use of Ibuprofen is associated with slower FEV1 decline in children with cystic fibrosis. Am J Respir Crit Care Med. 2007 Dec 1;176(11):1084-9. doi: 10.1164/rccm.200702-181OC. Epub 2007 Sep 13.
PubMed 17872492Kvale D, Ormaasen V, Kran AM, Johansson CC, Aukrust P, Aandahl EM, Froland SS, Tasken K. Immune modulatory effects of cyclooxygenase type 2 inhibitors in HIV patients on combination antiretroviral treatment. AIDS. 2006 Apr 4;20(6):813-20. doi: 10.1097/01.aids.0000218544.54586.f1.
PubMed 16549964
Study at a glance
From the registry record, last updated by the sponsor on 3 Apr 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double-Blind Randomized Placebo Controlled Trial for Prevention of Tuberculosis-Immune Reconstitution Inflammatory Syndrome With Non-Steroid Anti-Inflammatory Drugs (NSAIDs) in HIV-Infected Adults
- ClinicalTrials.gov ID
- NCT02060006
- Acronym / sponsor ID
- PRO13060453
- Conditions
- Tuberculosis
- Keywords
- TB, IRIS
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- University of StellenboschUniversity, hospital or other
- Collaborators
- University of Pittsburgh
- Study start
- Apr 2014
- Primary completion
- Apr 2015 (estimated)
- Study completion
- Apr 2015
- First posted
- 11 Feb 2014 (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.
Background: Non-Steroid Anti-Inflammatory Drugs (NSAIDs) reduce pain and inflammation by inhibiting cyclooxygenase, an enzyme in the pathway for formation of prostaglandins and thromboxane. Prior studies have proven the role of ibuprofen (an NSAID) in modulating lung injury and decreasing pulmonary damage in cystic fibrosis. While there has been an intense effort by the scientific community to define the best treatment strategies for tuberculosis immune reconstitution inflammatory syndrome (TB-IRIS), to our knowledge there is no available study evaluating preventive strategies using anti-inflammatory agents for TB-IRIS, a highly morbid complication in HIV-infected TB patients initiating antiretroviral therapy (ART).
Design and Methods: We propose to conduct a single center double-blind placebo-controlled randomized trial to investigate the efficacy of daily self-administered Meloxicam (a NSAID) versus placebo for prevention of Tuberculosis associated Immune Reconstitution Inflammatory Syndrome (TB-IRIS). A total of 150 HIV-infected adults who are treated for Tuberculosis for at least 2 weeks and about to initiate HIV treatment at Brewelskloof Hospital, Worcester, and Tygerberg Teaching Hospital, Cape Town, will be randomized to one of the following treatments: Meloxicam 7.5 mg tablet once-a-day, the experimental arm, versus Placebo tablet once-a-day, the control arm, for 8 weeks. All patients will be followed up for 12 months. Primary efficacy outcome: The decrease of the incidence of paradoxical TB IRIS by at least 20%; Primary safety outcome: The proportion of patients who temporarily or permanently discontinue Meloxicam due to any adverse event (e.g. dyspepsia or gastro-intestinal upset). Secondary outcomes are: 1) the proportion of patients in each arm with the following indicators of TB-IRIS severity/quality of life (QOL) (degree of pain or discomfort >III, presence of local or disseminated suppuration/abscess of any site, unscheduled clinic visits, hospitalizations, missed more than a day at work, etc; 2) The incidence of other types of IRIS (e.g. Kaposi Sarcoma or cryptococcal meningitis).
This study will provide important and novel data on the feasibility and efficacy of using a cheap, widely available NSAID used in both developed and developing countries, as a preventive intervention for TB-IRIS that could be quickly put into practice if proven to be effective
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo 7.5 mg daily for 8 weeks | Placebo comparator | –Placebo 7.5 mg once-daily First 8 weeks of ART Only Control arm |
| Meloxicam 7.5 mg once-daily | Experimental | Drug: Meloxicam 7.5mg daily for 8 weeksMeloxicam 7.5mg once-daily for 8 weeks |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Males and non-pregnant females age 18 years of age or older
- Evidence of HIV-1 infection
- TB treatment (<2 weeks) and initiating EFV-based antiretroviral therapy as per the South African Department of Health Guidelines
- Living in the study site catchment area and having had a known address for more than 3 months
- Written informed consent
Key exclusion criteria (10 listed)
- History of aspirin sensitivity and allergies to other NSAIDs
- Current or recent use (<3 months) of aspirin, NSAIDs, or anticoagulants such as warfarin.
- Current or recent use of corticosteroid therapy
- History of gastro-intestinal bleeding or peptic ulcer
- History of cardiovascular thrombotic events (myocardial infarction or stroke), hypertension, or congestive heart failure
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 |
|---|---|---|
| Meloxicam 7.5mg daily for 8 weeksAlso: Cox-2 InhibitorMeloxicam 7.5mg daily for 8 weeks | Drug | Meloxicam 7.5 mg once-daily |
Primary outcome
Incidence of TB IRIS
Time frame: 6 months
3 secondary outcomes
Proportion discontinuing Meloxicam due to adverse event
Time frame: 6 months
The proportion of patients in each arm with the following indicators of TB-IRIS severity/quality of life (QOL) (degree of pain or discomfort >III
Time frame: 6 months
The proportion of patients with local or disseminated suppuration/abscess of any site, unscheduled clinic visits, hospitalizations, missed more than a day at work, etc
Time frame: 6 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Apr 2014.
- Background: PubMed 20160249Eshun-Wilson I, Havers F, Nachega JB, Prozesky HW, Taljaard JJ, Zeier MD, Cotton M, Simon G, Soentjens P. Evaluation of paradoxical TB-associated IRIS with the use of standardized case definitions for resource-limited settings. J Int Assoc Physicians AIDS Care (Chic). 2010 Mar-Apr;9(2):104-8. doi: 10.1177/1545109710361537. Epub 2010 Feb 16.
- Background: PubMed 20808204Meintjes G, Wilkinson RJ, Morroni C, Pepper DJ, Rebe K, Rangaka MX, Oni T, Maartens G. Randomized placebo-controlled trial of prednisone for paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome. AIDS. 2010 Sep 24;24(15):2381-90. doi: 10.1097/QAD.0b013e32833dfc68.
- Background: PubMed 18652998Meintjes G, Lawn SD, Scano F, Maartens G, French MA, Worodria W, Elliott JH, Murdoch D, Wilkinson RJ, Seyler C, John L, van der Loeff MS, Reiss P, Lynen L, Janoff EN, Gilks C, Colebunders R; International Network for the Study of HIV-associated IRIS. Tuberculosis-associated immune reconstitution inflammatory syndrome: case definitions for use in resource-limited settings. Lancet Infect Dis. 2008 Aug;8(8):516-23. doi: 10.1016/S1473-3099(08)70184-1.
- Background: PubMed 20181971Abdool Karim SS, Naidoo K, Grobler A, Padayatchi N, Baxter C, Gray A, Gengiah T, Nair G, Bamber S, Singh A, Khan M, Pienaar J, El-Sadr W, Friedland G, Abdool Karim Q. Timing of initiation of antiretroviral drugs during tuberculosis therapy. N Engl J Med. 2010 Feb 25;362(8):697-706. doi: 10.1056/NEJMoa0905848.
- Background: PubMed 22010913Blanc FX, Sok T, Laureillard D, Borand L, Rekacewicz C, Nerrienet E, Madec Y, Marcy O, Chan S, Prak N, Kim C, Lak KK, Hak C, Dim B, Sin CI, Sun S, Guillard B, Sar B, Vong S, Fernandez M, Fox L, Delfraissy JF, Goldfeld AE; CAMELIA (ANRS 1295-CIPRA KH001) Study Team. Earlier versus later start of antiretroviral therapy in HIV-infected adults with tuberculosis. N Engl J Med. 2011 Oct 20;365(16):1471-81. doi: 10.1056/NEJMoa1013911.
- Background: PubMed 22010914Havlir DV, Kendall MA, Ive P, Kumwenda J, Swindells S, Qasba SS, Luetkemeyer AF, Hogg E, Rooney JF, Wu X, Hosseinipour MC, Lalloo U, Veloso VG, Some FF, Kumarasamy N, Padayatchi N, Santos BR, Reid S, Hakim J, Mohapi L, Mugyenyi P, Sanchez J, Lama JR, Pape JW, Sanchez A, Asmelash A, Moko E, Sawe F, Andersen J, Sanne I; AIDS Clinical Trials Group Study A5221. Timing of antiretroviral therapy for HIV-1 infection and tuberculosis. N Engl J Med. 2011 Oct 20;365(16):1482-91. doi: 10.1056/NEJMoa1013607.
- Background: PubMed 17872492Konstan MW, Schluchter MD, Xue W, Davis PB. Clinical use of Ibuprofen is associated with slower FEV1 decline in children with cystic fibrosis. Am J Respir Crit Care Med. 2007 Dec 1;176(11):1084-9. doi: 10.1164/rccm.200702-181OC. Epub 2007 Sep 13.
- Background: PubMed 16549964Kvale D, Ormaasen V, Kran AM, Johansson CC, Aukrust P, Aandahl EM, Froland SS, Tasken K. Immune modulatory effects of cyclooxygenase type 2 inhibitors in HIV patients on combination antiretroviral treatment. AIDS. 2006 Apr 4;20(6):813-20. doi: 10.1097/01.aids.0000218544.54586.f1.
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Meloxicam 7.5mg daily for 8 weeks in people with Tuberculosis, run by University of Stellenbosch at 1 site in South Africa.
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 5 inclusion and 10 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: status not confirmed, as of the sponsor's last update on 3 Apr 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in South Africa. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Jean B Nachega, MD, PhD (+27 21 938 9933, JNACHEGA@SUN.AC.ZA), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of TB IRIS (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02060006, which also lists 8 linked publications.
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 3 Apr 2014.