Clinical trial NCT01602861: The Effects of Spironolactone on Calcineurin Inhibitor Induced Nephrotoxicity
Official title: The Effects of Spironolactone on Calcineurin Inhibitor Induced Nephrotoxicity
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Disorder Related to Renal Transplantation
Keywords: Fibrosis
calcineurin inhibitor
kidney transplant
chronic rejection
Lead sponsor: Odense University Hospital
Sponsor class: OTHER
Collaborators: name: Fredericia Hosptial
First posted: 2012-05-21
Enrollment: 188
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in Cr EDTA clearance
timeFrame: 0, 1 year, 2 years, 3 years
Secondary outcomes:
measure: Reduced urine protein levels (change from baseline)
timeFrame: 0, 1 year, 2 years, 3 years
measure: Reduced fibrosis (change from baseline)
timeFrame: 0, 2 years
measure: Reduced blood pressure (change from baseline)
timeFrame: 0, 1 year, 2 years, 3 years
measure: Cardiovascular events
timeFrame: 3 years
Other outcomes:
Locations:
city: Odense C
country: Denmark
facility: Odense University Hospital
Study officials:
affiliation: Dep. of Nephrology, Odense University Hospital
name: Claus Bistrup, MD, ph.d.
role: STUDY_DIRECTOR
References:
citation: Mortensen LA, Thiesson HC, Tougaard B, Egfjord M, Fischer ASL, Bistrup C. The effect of spironolactone on calcineurin inhibitor induced nephrotoxicity: a multicenter randomized, double-blind, clinical trial (the SPIREN trial). BMC Nephrol. 2018 May 3;19(1):105. doi: 10.1186/s12882-018-0885-6.