The Effects of Spironolactone on Calcineurin Inhibitor Induced Nephrotoxicity

Phase 4

Completed

• Conditions: Disorder Related to Renal Transplantation
• Interventions: Drug: Spironolactone; Drug: placebo

• Registration Number: NCT01602861
• Lead Sponsor: Odense University Hospital

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.

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 Timeline

• Study First Submitted: 2012-05-17
• Study First Submitted QC: 2012-05-18
• Study First Posted: 2012-05-21
• Study Start: 2013-02
• Primary Completion: 2021-04
• Study Completion: 2021-04
• Status Verified: 2021-09
• Last Update Submitted: 2021-09-08
• Last Update Posted: 2021-09-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 188

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Spironolactone	Spironolactone	-
Placebo	placebo	-

Primary Outcome Measures

Name	Time	Method
Change in Cr EDTA clearance	0, 1 year, 2 years, 3 years

Secondary Outcome Measures

Name	Time	Method
Reduced blood pressure (change from baseline)	0, 1 year, 2 years, 3 years
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.
Cardiovascular events	3 years

Trial Locations

Locations (1)

Odense University Hospital; 🇩🇰 Odense C, Denmark