The use of steroids in conjunction with antiretroviral therapy to treat HIV associated nephropathy to assist with treatment of renal function
| ISRCTN | ISRCTN56112439 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN56112439 |
| Secondary identifying numbers | HREC:241/2007 |
- Submission date
- 20/08/2018
- Registration date
- 05/09/2018
- Last edited
- 24/04/2019
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Urological and Genital Diseases
Plain English summary of protocol
Background and study aims [objectives and aims]
Despite the success of antiretroviral therapies, HIV-related kidney disease still carries a significant risk of kidney failure (end-stage renal disease). HIV-associated nephropathy (HIVAN) is a type of kidney disease that has a large risk for end-stage renal disease, and without antiretroviral therapy, it can rapidly progress to end-stage renal disease. Moreover, some patients still have worsening kidney function and disease progression, despite using the correct antiretroviral therapies. This can be explained by the kidneys acting as a reservoir for HIV, and the fact that antiretroviral therapy is unable to access the kidneys.
Kidney diseases can be treated with drugs called corticosteroids. Research has looked at the effectiveness and safety of using corticosteroids with antiretroviral therapy for the treatment of HIVAN; however, this research is incomplete and more studies are required. This study aims to look at the balance between an improvement in kidney function and side effects with the use of corticosteroids as an add-on to antiretroviral therapy in patients with HIVAN.
Who can participate?
HIV positive adults with unexplained kidney impairment, proteinuria and/or haematuria, who have undergone renal biopsy
What does the study involve?
All patients will be given antiretroviral therapy. They will then be randomly allocated to receive add-on corticosteroids or antiretroviral therapy only. Those allocated to receive corticosteroids had this treatment slowly reduced over a 6 month protein. All patients were offered additional medication to control proteinuria if their blood pressure meant they could tolerate this. Additionally, all patients were given medication to prevent other diseases such as tuberculosis. Patients were tested for improvements in kidney function every month for the 6 month study period and then every 3 months for 2 years after the study.
What are the possible benefits and risks of participating?
The possible benefits of participating include possible improvement in renal function and proteinuria with the addition of corticosteroids and regular patient review. All patients on the study remained as patients in the clinic after the trial finished. There is a possible risk of infection as a result of corticosteroid use; however, preventative medication will be given and patients will be monitored closely for any kind of infection.
Where is the study run from?
Groote Schuur Hospital Cape Town (South Africa)
When is the study starting and how long is it expected to run for?
May 2007 to May 2017
Who is funding the study?
This study is self-funded, as all aspects were part of routine clinical practice
Who is the main contact?
Associate Professor Nicola Wearne
nicola.wearne@uct.ac.za
Contact information
Scientific
11 feldhausen ave
Claremont
Cape Town
7708
South Africa
Study information
| Study design | Interventional prospective open-label randomised controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use contact details (nicola.wearne@uct.ac.za) to request a participant information sheet |
| Scientific title | The effects of add-on corticosteroids on renal outcomes in patients with biopsy-proven HIV-associated nephropathy: a single centre study from South Africa |
| Study objectives | Corticosteroids will improve renal outcomes (i.e. eGFR and proteinuria) in HIV-associated nephropathy in patients also initiated on antiretroviral therapy. |
| Ethics approval(s) | Human Research Ethics Committee of the University of Cape Town South Africa, 24/07/2007, HREC:241/2007 |
| Health condition(s) or problem(s) studied | HIV associated nephropathy |
| Intervention | Participants were randomly allocated to 1 of 2 groups - either antiretroviral therapy (ART) and corticosteroids (1 mg/kg prednisone), or ART alone. Patients were assigned their treatment by randomly selecting a sealed opaque envelope with the treatment allocation. Both investigator and patients were not blinded during the study period as additional prophylactic treatment (i.e. cotrimoxazole, isoniazid) was required to prevent opportunistic infections in those receiving ART and corticosteroids. The maximum dose of ART was 60 mg/day regardless of body weight. Prednisone was tapered over a 6 month period by 10 mg per month. All patients were given angiotensin converting enzyme inhibition (ACEi) or angiotensin receptor blockade (ARB), if their blood pressure and renal function could tolerate it (this is standard care for proteinuria). Isoniazid and cotrimoxazole was started in those patients offered corticosteroids for tuberculosis and pneumocystis jirovecii prophylaxis. Patients were followed up monthly for 6 months and then every 3 months for 2 years. After the 2 year period the patients remain in the HIV renal clinic and are followed up as required clinically. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Not Specified |
| Drug / device / biological / vaccine name(s) | Prednisone |
| Primary outcome measure | Improvement in the following renal outcomes in patients with glomerular or tubulointerstitial features of HIVAN as a result of corticosteroid therapy, from the at the baseline, then monthly for 6 months, then every 3 months for 2 years: 1. Improvement in estimated glomerular filtration rate (eGFR), assessed using the CKD EPI formula 2. Serum creatinine (mol/l), assessed using a blood test 3. Urine protein/creatinine ratio (uPCR) (g/mmol), assessed using a blood test |
| Secondary outcome measures | 1. Adverse events, assessed using death certificates, patient folders, records from HIV clinics and family members at every 3 months during the 2 year follow-up period 2. Improvements in the following histologies, assessed using a renal biopsy at the baseline and after 6 months: 2.1. Podocytopathy 2.2. Interstitial fibrosis 2.3. Lymphocytic cell infiltration 2.4. Plasma cell infiltration |
| Overall study start date | 24/05/2007 |
| Completion date | 18/05/2017 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 40 patients (20 in each arm) |
| Key inclusion criteria | 1. Histologically-proven HIV-associated nephropathy, defined as having the presence of chronic tubulointerstitial inflammation with plasma cells, lymphocytes and microcysts, along with any of the following: 1.1. Collapsing glomerulopathy 1.2. Focal segmental glomerulosclerosis 1.3. Podocyte hypertrophy and/or hyperplasia 2. Antiretroviral therapy naïve for at least 2 weeks prior to renal biopsy 3. Initiation of antiretroviral therapy within 1 month of the renal biopsy 3. Aged 18 years or older 4. Able to provide written informed consent |
| Key exclusion criteria | 1. Any active infection 2. Kaposi sarcoma 3. Active cytomegalovirus 4. Inability to follow-up at study centre |
| Date of first enrolment | 01/04/2010 |
| Date of final enrolment | 18/05/2015 |
Locations
Countries of recruitment
- South Africa
Study participating centre
Cape Town
7708
South Africa
Sponsor information
Hospital/treatment centre
Anzio Road
Cape Town
7708
South Africa
"ROR" |
https://ror.org/00c879s84 |
|---|
Funders
Funder type
Not defined
No information available
Results and Publications
| Intention to publish date | 01/09/2018 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | We intend to publish in BMC Nephrology in 2018. |
| IPD sharing plan | Any data from this study is available on request. There is an Excel spreadsheet with STATA analysis. All information is stored in a password protected file. Patients have given consent to data distribution. All data will be made available by Prof Nicola Wearne [ Nicola.wearne@uct.ac.za] |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | results | 06/02/2019 | Yes | No | |
| Basic results | 05/09/2018 | 24/04/2019 | No | No |
Additional files
- ISRCTN56112439 _BasicResults_05Sep2018.pdf
- uploaded 24/04/2019
Editorial Notes
24/04/2019: The basic results of this trial have been uploaded as an additional file.
22/02/2019: Internal review. The drug name and phase have been added.
11/02/2019: Publication reference added.
21/09/2018: Internal review
