Does Lisinopril protect transplanted kidneys with chronic vascular rejection (CR) from progressive failure?
| ISRCTN | ISRCTN76140647 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN76140647 |
| Secondary identifying numbers | 1720 |
- Submission date
- 02/09/2005
- Registration date
- 09/09/2005
- Last edited
- 14/06/2011
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Surgery
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Plain English Summary
Not provided at time of registration
Contact information
Dr Rana Rustom
Scientific
Scientific
School of Clinical Science
Metabolic and Cellular Division
Duncan Building
Liverpool
L69 3GA
United Kingdom
| Phone | +44 (0)151 706 4663/4070 |
|---|---|
| rana.rustom@liv.ac.uk |
Study information
| Study design | Randomised controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Scientific title | |
| Study hypothesis | Proteinuria and progression to end-stage renal failure are closely linked in patients with diseased native kidneys. ACE-inhibitors are known to reduce proteinuria and ameliorate the rate of decline of renal function. Data are lacking in kidney transplant patients with proteinuria and chronic allograft nephropathy (CAN). Do comparable beneficial effects of ACE-inhibitors also apply in transplant patients? Publications resulting from small clinical studies were needed to design this trial as no previous data was available: Rustom R et al: Effects of Angiotensin-converting-enzyme inhibitors (ACE-i) on progression to end-stage renal failure in chronic vascular rejection (CR). Transplantation Proceedings 2001, 33:1175-1176. Rustom R et al: Renal tubular peptide catabolism, injury & ammonia excretion in patients with chronic vascular rejection: effects of Lisinopril. Renal Failure 2001, 23:517-531. Bone JM, Amara AB, Shenkin A, Hammad A, Sells RA, Alexander J, McArdle F, Rustom R: Calcineurin inhibitors and proximal renal tubular injury in renal transplant patients with proteinuria and chronic allograft nephropathy. Transplantation 2005, 79:119-122. |
| Ethics approval(s) | Not provided at time of registration |
| Condition | End-stage renal failure |
| Intervention | Use of Lisinopril in the active limb only (dose used titrated in individual patients to achieve maximum reduction in proteinuria without leading to postural hypotension). Control: usual care There is very close attention to detail and all patients regardless of which limb in the trial have strict blood pressure control, as well as treatment of their anaemia, metabolic acidosis and secondary hyperparathyroidism. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Not Specified |
| Drug / device / biological / vaccine name(s) | Lisinopril |
| Primary outcome measure | Preservation of glomerular filtration rate (GFR) ml/min. |
| Secondary outcome measures | 1. Reduction in proteinuria 2. Sub-group analyses: 2.1 Effects on tubular metabolism of aprotinin (lisinopril limb only) 2.2 Urinary NAG, MCP-1, TGF-Beta 2.3 Plasma markers of oxidative stress 2.4 ACE genotyping |
| Overall study start date | 01/09/2000 |
| Overall study end date | 30/09/2006 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Upper age limit | 70 Years |
| Sex | Both |
| Target number of participants | 42 |
| Participant inclusion criteria | 1. Biopsy proven CAN at least 6 months post kidney transplantation - both cadaveric and live-related. Each biopsy will be independently examined and the severity graded by an experienced pathologist 2. Not on ACE-inhibitor (or angiotensin II antagonists) treatment 3. Patients may be on any combination of immunosuppressive therapy. However, those who have been converted to tacrolimus or mycophenolate mofetil after diagnosis of CAN within 6 months are excluded 4. Proteinuria of more than 1.0 g/24 hours 5. Mean creatinine clearance >20 ml/min 6. No history of a transient ischaemic or cardiovascular event or malignancy in the last 6 months 7. Patients aged between 18-70 years |
| Participant exclusion criteria | 1. Patients with clinical or histological evidence or acute rejection in the last 3 months 2. Patients with evidence of renal artery stenosis 3. Persistently high cyclosporin or tacrolimus levels 4. Abnormal liver function tests 5. Pregnant or ineffective contraception 6. Chronic intractable cough |
| Recruitment start date | 01/09/2000 |
| Recruitment end date | 30/09/2006 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
School of Clinical Science
Liverpool
L69 3GA
United Kingdom
L69 3GA
United Kingdom
Sponsor information
Royal Liverpool and Broad Green University Hospitals NHS Trust (UK)
Hospital/treatment centre
Hospital/treatment centre
Prescot Street
Liverpool
L7 8XP
England
United Kingdom
| Phone | +44 (0)151 706 2000 |
|---|---|
| Jacqui.Pirmohamed@rlbuht.nhs.uk | |
| Website | http://www.rlbuht.nhs.uk |
"ROR" |
https://ror.org/009sa0g06 |
Funders
Funder type
University/education
Mersey Kidney Research (Ref No: R1975/1) (UK)
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 | 15/01/2010 | Yes | No |
