The Effects of Spironolactone on Calcineurin Inhibitor Induced Nephrotoxicity

Disorder Related to Renal Transplantation Clinical Trial

— SPIREN  

Official title:

The Effects of Spironolactone on Calcineurin Inhibitor Induced Nephrotoxicity

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01602861
• Other study ID #: Eudra CT: 2011-002243-98
• Status: Completed
• Phase: Phase 4
• Start date: February 2013
• Est. completion date: April 2021

Study information

• Verified date: September 2021
• Source: Odense University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 188
• Est. completion date: April 2021
• Est. primary completion date: April 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Age > 18 years

2. Proteinuria < 3 g/24 hours

3. Creatinine clearance = 30 mL/min

4. S-Potassium < 5,5 mmol/L

5. Negative pregnancy test at the inclusion and anticonception

Exclusion Criteria:

1. Intolerance to spironolactone

2. Creatinine clearance < 30 ml/min

3. S-Potassium = 5,5 mmol/L

4. Resin or digoxine treatment

5. Pregnancy or planned pregnancy

6. Relevant organic, systemic or mental illness

7. Anticipation of lack of compliance or understanding the study

Related Conditions & MeSH terms

• Disorder Related to Renal Transplantation

Intervention

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

Locations

Country	Name	City	State
Denmark	Odense University Hospital	Odense C

Sponsors (2)

Lead Sponsor	Collaborator
Odense University Hospital	Fredericia Hosptial

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Cr EDTA clearance		0, 1 year, 2 years, 3 years
Secondary	Reduced urine protein levels (change from baseline)		0, 1 year, 2 years, 3 years
Secondary	Reduced fibrosis (change from baseline)	Verified by graft biopsies and immuno histochemistry. Newly transplanted patients will be subjected to additional biopsies 3 months and 1 year after inclusion.	0, 2 years
Secondary	Reduced blood pressure (change from baseline)		0, 1 year, 2 years, 3 years
Secondary	Cardiovascular events		3 years