The Effects of Spironolactone on Calcineurin Inhibitor Induced Nephrotoxicity (SPIREN)

This study is enrolling participants by invitation only.
Sponsor:
Collaborator:
Fredericia Hosptial
Information provided by (Responsible Party):
Line Aas Mortensen, Odense University Hospital
ClinicalTrials.gov Identifier:
NCT01602861
First received: May 17, 2012
Last updated: January 23, 2014
Last verified: January 2014
  Purpose

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 Intervention Phase
Disorder Related to Renal Transplantation
Drug: Spironolactone
Drug: placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: The Effects of Spironolactone on Calcineurin Inhibitor Induced Nephrotoxicity

Resource links provided by NLM:


Further study details as provided by Odense University Hospital:

Primary Outcome Measures:
  • Improved Cr EDTA clearance [ Time Frame: 0, 1 year, 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Reduced urine protein levels [ Time Frame: Every 3 months ] [ Designated as safety issue: No ]
  • Reduced fibrosis [ Time Frame: 0, 2 years ] [ Designated as safety issue: No ]
    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 [ Time Frame: 0, 1 year, 2 years ] [ Designated as safety issue: No ]
  • Cardiovascular events [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 170
Study Start Date: February 2013
Estimated Study Completion Date: September 2017
Estimated Primary Completion Date: September 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01602861

Locations
Denmark
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
  More Information

No publications provided

Responsible Party: Line Aas Mortensen, Principal Investigator, Odense University Hospital
ClinicalTrials.gov Identifier: NCT01602861     History of Changes
Other Study ID Numbers: Eudra CT: 2011-002243-98
Study First Received: May 17, 2012
Last Updated: January 23, 2014
Health Authority: Denmark: Danish Dataprotection Agency
Denmark: Ethics Committee
Denmark: Danish Medicines Agency

Keywords provided by Odense University Hospital:
Fibrosis
calcineurin inhibitor
kidney transplant
chronic rejection

Additional relevant MeSH terms:
Spironolactone
Aldosterone Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Diuretics
Natriuretic Agents
Cardiovascular Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 17, 2014