A randomised controlled trial of prednisone versus placebo in the management of human immunodeficiency virus (HIV)-infected patients presenting with mild to moderate Tuberculosis-associated Immune Reconstitution Inflammatory Syndrome after commencing Highly Active Antiretroviral Therapy
| ISRCTN | ISRCTN21322548 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN21322548 |
| Secondary identifying numbers | TB-IRIS-RCT |
- Submission date
- 03/06/2005
- Registration date
- 17/08/2005
- Last edited
- 17/08/2012
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Infections and Infestations
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Plain English Summary
Not provided at time of registration
Contact information
Prof Gary Maartens
Scientific
Scientific
Division of Pharmacology
University of Cape Town Medical School
K45
Old Main Building
Groote Schuur Hospital
Cape Town
7925
South Africa
Study information
| Study design | Randomised placebo-controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Not specified |
| Study type | Treatment |
| Scientific title | |
| Study acronym | TB-IRIS-RCT |
| Study hypothesis | We propose a randomised placebo-controlled trial of prednisone as an adjunct in the management of HIV-infected patients with mild to moderate Tuberculosis-associated Immune Reconstitution Inflammatory Syndrome (TB-IRIS). This syndrome manifests as a paradoxical worsening of clinical features of tuberculosis after commencing Highly Active Antiretroviral Therapy (HAART). We hypothesise a reduction in the requirement for hospitalisation and therapeutic procedures among patients receiving prednisone. |
| Ethics approval(s) | Not provided at time of registration |
| Condition | HIV and Tuberculosis-associated Immune Reconstitution Inflammatory Syndrome |
| Intervention | Randomization to oral prednisone 1.5 mg/kg for 2 weeks followed by 0.75 mg/kg for 2 weeks or identical placebo medication. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Not Specified |
| Drug / device / biological / vaccine name(s) | Prednisone |
| Primary outcome measure | Combined hospitalisation and procedures endpoint (cumulative duration of hospitalisation in days + outpatient therapeutic procedures counted as one day) |
| Secondary outcome measures | Radiological Endpoints: A significant improvement in radiological manifestations of IRIS: 1. For Chest X Ray pulmonary infiltrates, a significant reduction in composite infiltrate score (6 zones each measured for degree of infiltrate by Radiologist to give composite score) 2. For large nodes noted on the Chest X Ray, a significant reduction in size 3. For computed tomography (CT) scans, a significant reduction in infiltrate or node size 4. For peripheral & abdominal nodes, a significant reduction in volume as measured by ultrasound 5. For cold abscesses, a significant reduction in volume as measured by ultrasound Other Secondary Endpoints: 1. 50% reduction in symptom score (Wilson 2004) 2. A significant improvement in the Quality of Life MOS-HIV score 3. Improvement in Karnofsky score of greater than 10 4. Corticosteroid side effects a. New onset of diabetes b. New onset of hypertension c. Psychological side effects d. Onset of new opportunistic infection/cancer such as Kaposis sarcoma, Herpes simplex lesions, Herpes zoster lesions 5. 50% reduction in C-Reactive Protein (CRP) value 6. Weight gain 7. Mortality 8. The need to stop HAART, TB therapy or study drug 9. Adherence with HAART and study drug as assessed by pill count and adherence with TB treatment as assessed by TB clinic card assessment 10. Recurrence of IRIS manifestations within the 12 week study period 11. In patients with an Alkaline Phosphatase or gamma glutamyl transpeptidase (GGT) that was elevated more than 2 x upper limit of normal (ULN) at baseline, a reduction of 50% from the baseline value 12. CD4 and Viral load 13. For ascites, reduction in abdominal girth |
| Overall study start date | 01/06/2005 |
| Overall study end date | 31/05/2007 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 100 |
| Participant inclusion criteria | A. Age 18 years and over B. Informed consent (written) C. Prior to the introduction of HAART the following criteria must be met for the diagnosis of TB-IRIS to be considered: 1. The patient has HIV infection 2. The patient should be antiretroviral-naïve (excluding receipt of antiretroviral treatment within mother to child transmission programmes Nevirapine single-dose with or without Zidovudine in the third trimester) 3. The patient has microbiologic, histologic or very strong clinical evidence of tuberculosis 4. There has been a documented improvement in symptoms, Karnofsky score and/or weight, resolution of fever and clinical and radiological stabilization during the intensive phase of multidrug TB therapy 5. That adherence with anti-TB treatment is >80% 6. That the infecting strain of M. tuberculosis is sensitive to rifampicin, if this result is available D. Consider TB-IRIS if, within 3 months of the introduction of multi-drug HAART 1. Adherence with HAART is documented and the patient was on anti-tuberculous therapy when HAART commenced 2. There are new or recurrent constitutional symptoms PLUS one or more of: i. New or expanding lymph nodes (>20 mm or >50% in volume) ii. New or expanding tuberculous cold abscesses (e.g. paraspinal) iii. New or expanding pulmonary infiltrates (radiographically confirmed) iv. New or enlarging serous effusions (pericardial, pleural or ascitic) Patients presenting with other manifestations of TB-IRIS (e.g. central nervous system [CNS] tuberculoma) will not be included in this study. |
| Participant exclusion criteria | 1. Previous systemic steroid therapy as part of the management of tuberculosis 2. Pregnancy 3. Uncontrolled Diabetes Mellitus 4. Adrenal failure 5. Severe TB-IRIS (these cases will receive open label corticosteroids) manifested by: a. Respiratory failure (pO2 <8 kPa) b. Altered level of consciousness or new focal neurological signs c. Compression of vital structures (e.g. bronchostenosis) 6. Kaposis sarcoma |
| Recruitment start date | 01/06/2005 |
| Recruitment end date | 31/05/2007 |
Locations
Countries of recruitment
- South Africa
Study participating centre
Division of Pharmacology
Cape Town
7925
South Africa
7925
South Africa
Sponsor information
University of Cape Town - Research Ethics Committee, Faculty of Health Sciences (South Africa)
University/education
University/education
Research Ethics Committee
Faculty of Health Sciences
Old Main Building
Groote Schuur Hospital
Observatory
Cape Town
7925
South Africa
"ROR" |
https://ror.org/03p74gp79 |
|---|
Funders
Funder type
Research council
Medical Research Council, South Africa (no reference number provided)
No information available
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | results | 15/08/2012 | Yes | No |
