Condition category
Surgery
Date applied
02/09/2005
Date assigned
09/09/2005
Last edited
14/06/2011
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Dr Rana Rustom

ORCID ID

Contact details

School of Clinical Science
Metabolic and Cellular Division
Duncan Building
Liverpool
L69 3GA
United Kingdom
+44 (0)151 706 4663/4070
rana.rustom@liv.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

1720

Study information

Scientific title

Acronym

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

Not provided at time of registration

Study design

Randomised controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

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

Phase

Not Specified

Drug names

Lisinopril

Primary outcome measures

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 trial start date

01/09/2000

Overall trial end date

30/09/2006

Reason abandoned

Eligibility

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 type

Patient

Age group

Adult

Gender

Both

Target number of participants

42

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

United Kingdom

Trial participating centre

School of Clinical Science
Liverpool
L69 3GA
United Kingdom

Sponsor information

Organisation

Royal Liverpool and Broad Green University Hospitals NHS Trust (UK)

Sponsor details

Prescot Street
Liverpool
L7 8XP
United Kingdom
+44 (0)151 706 2000
Jacqui.Pirmohamed@rlbuht.nhs.uk

Sponsor type

Government

Website

http://www.rlbuht.nhs.uk

Funders

Funder type

University/education

Funder name

Mersey Kidney Research (Ref No: R1975/1) (UK)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

2010 results in http://www.ncbi.nlm.nih.gov/pubmed/20061926

Publication citations

  1. Results

    Amara AB, Sharma A, Alexander JL, Alfirevic A, Mohiuddin A, Pirmohamed M, Close GL, Grime S, Maltby P, Shawki H, Heyworth S, Shenkin A, Smith L, Sharma AK, Hammad A, Rustom R, Randomized controlled trial: lisinopril reduces proteinuria, ammonia, and renal polypeptide tubular catabolism in patients with chronic allograft nephropathy., Transplantation, 2010, 89, 1, 104-114, doi: 10.1097/TP.0b013e3181bf13d9.

Additional files

Editorial Notes