SPIREN: The Effects of Spironolactone on Calcineurin Inhibitor Induced Nephrotoxicity

Sponsor

Odense University Hospital (Other)

Overall Status

Completed

CT.gov ID

NCT01602861

Collaborator

Fredericia Hosptial (Other)

188

Enrollment

Location

Arms

97.9

Duration (Months)

1.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to assess whether the diuretic drug spironolactone can prevent chronic damage to transplanted kidneys caused by the medication that prevents rejection.

Spironolactone prevents the effects of the hormone aldosterone. Aldosterone is suspected of being involved in the processes leading to chronic rejection of transplanted kidneys. Hence, by blocking the effects of aldosterone we hope to be able to prevent loss of kidney function in transplant patients.

Condition or Disease	Intervention/Treatment	Phase
Disorder Related to Renal Transplantation	Drug: Spironolactone Drug: placebo	Phase 4

Detailed Description

AIM: The purpose of this study is to assess whether spironolactone can prevent the formation of fibrosis in transplanted kidneys.

BACKGROUND: Calcineurin inhibitors (CNI) are one of the cornerstones of immunosuppressive therapy after kidney transplantation. The introduction of CNI has caused a significant decrease in acute rejections. However, CNI also have known side effects. These include the formation of tubulointerstitial fibrosis in the transplanted kidney, contributing over time to impaired kidney function and reduced graft survival.

The mineralocorticoid aldosterone may be involved in the development of renal fibrosis. Recent observations suggest that aldosterone plays a central role in the pathogenesis of CNI nephrotoxicity and that the mineralocorticoid-receptor-blocker spironolactone could be a useful agent to prevent it.

METHODS: This study is a randomized, placebo-controlled, double-blind study in which 170 renal transplant patients will be recruited from two nephrological departments in Southern Denmark. Patients will be randomized to three years of treatment with either spironolactone or placebo added to the standard immunosuppressive treatment. Renal graft biopsies, various molecular tests of tissue, blood and urine, chrome-EDTA clearance, 24-hour bloodpressure measurement and blood samples will be performed at inclusion, after 1 year, 2 years and upon completion.

Study Design

Study Type:

Interventional

Actual Enrollment :

188 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Prevention

Official Title:

The Effects of Spironolactone on Calcineurin Inhibitor Induced Nephrotoxicity

Study Start Date :

Feb 1, 2013

Actual Primary Completion Date :

Apr 1, 2021

Actual Study Completion Date :

Apr 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Spironolactone	Drug: Spironolactone One tablet per day (25 mg Spironolactone/placebo) for the first three months. Subsequently dosage is increased to two tablets per day (50 mg Spironolactone/placebo) for the rest of the study. In case of hyperkaliemia (>5,5 mmol/L) or intolerable side effects dosage will be reduced to one tablet per day (25 mg Spironolactone/placebo).
Placebo Comparator: Placebo	Drug: placebo

Arm

Intervention/Treatment

Experimental: Spironolactone

Drug: Spironolactone

One tablet per day (25 mg Spironolactone/placebo) for the first three months. Subsequently dosage is increased to two tablets per day (50 mg Spironolactone/placebo) for the rest of the study. In case of hyperkaliemia (>5,5 mmol/L) or intolerable side effects dosage will be reduced to one tablet per day (25 mg Spironolactone/placebo).

Placebo Comparator: Placebo

Drug: placebo

Outcome Measures

Primary Outcome Measures

Change in Cr EDTA clearance [0, 1 year, 2 years, 3 years]

Secondary Outcome Measures

Reduced urine protein levels (change from baseline) [0, 1 year, 2 years, 3 years]
Reduced fibrosis (change from baseline) [0, 2 years]
Verified by graft biopsies and immuno histochemistry. Newly transplanted patients will be subjected to additional biopsies 3 months and 1 year after inclusion.
Reduced blood pressure (change from baseline) [0, 1 year, 2 years, 3 years]
Cardiovascular events [3 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age > 18 years
Proteinuria < 3 g/24 hours
Creatinine clearance ≥ 30 mL/min
S-Potassium < 5,5 mmol/L
Negative pregnancy test at the inclusion and anticonception

Exclusion Criteria:

Intolerance to spironolactone
Creatinine clearance < 30 ml/min
S-Potassium ≥ 5,5 mmol/L
Resin or digoxine treatment
Pregnancy or planned pregnancy
Relevant organic, systemic or mental illness
Anticipation of lack of compliance or understanding the study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Odense University Hospital	Odense C		Denmark	5000

Sponsors and Collaborators

Odense University Hospital
Fredericia Hosptial

Investigators

Study Director: Claus Bistrup, MD, ph.d., Dep. of Nephrology, Odense University Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Line Aas Mortensen, Principal Investigator, Odense University Hospital

ClinicalTrials.gov Identifier:

NCT01602861

Other Study ID Numbers:

Eudra CT: 2011-002243-98

First Posted:

May 21, 2012

Last Update Posted:

Sep 9, 2021

Last Verified:

Sep 1, 2021

Keywords provided by Line Aas Mortensen, Principal Investigator, Odense University Hospital

Fibrosis

calcineurin inhibitor

kidney transplant

chronic rejection

Additional relevant MeSH terms:

Spironolactone

Study Results

No Results Posted as of Sep 9, 2021