Condition category
Urological and Genital Diseases
Date applied
20/08/2018
Date assigned
05/09/2018
Last edited
21/09/2018
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

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

Trial website

Contact information

Type

Scientific

Primary contact

Prof Nicola Wearne

ORCID ID

Contact details

11 feldhausen ave
Claremont
Cape Town
7708
South Africa

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

HREC:241/2007

Study information

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

Acronym

Study hypothesis

Corticosteroids will improve renal outcomes (i.e. eGFR and proteinuria) in HIV-associated nephropathy in patients also initiated on antiretroviral therapy.

Ethics approval

Human Research Ethics Committee of the University of Cape Town South Africa, 24/07/2007, HREC:241/2007

Study design

Interventional prospective open-label randomised controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use contact details (nicola.wearne@uct.ac.za) to request a participant information sheet

Condition

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

Phase

Drug names

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 trial start date

24/05/2007

Overall trial end date

18/05/2017

Reason abandoned (if study stopped)

Eligibility

Participant 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

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

40 patients (20 in each arm)

Participant exclusion criteria

1. Any active infection
2. Kaposi sarcoma
3. Active cytomegalovirus
4. Inability to follow-up at study centre

Recruitment start date

01/04/2010

Recruitment end date

18/05/2015

Locations

Countries of recruitment

South Africa

Trial participating centre

Groote Schuur Hospital
Anzio road, Observatory
Cape Town
7708
South Africa

Sponsor information

Organisation

GROOTE SCHUUR HOSPITAL/ UNIVERSITY OF CAPE TOWN

Sponsor details

Anzio Road
Cape Town
7708
South Africa

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Not defined

Funder name

SELF FUNDED

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

We intend to publish in BMC Nephrology in 2018.

IPD sharing statement:
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]

Intention to publish date

01/09/2018

Participant level data

Available on request

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

21/09/2018: Internal review