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

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ClinicalTrials.gov Identifier: NCT01602861
Recruitment Status : Unknown
Verified January 2014 by Line Aas Mortensen, Odense University Hospital.
Recruitment status was:  Enrolling by invitation
First Posted : May 21, 2012
Last Update Posted : January 24, 2014
Fredericia Hosptial
Information provided by (Responsible Party):
Line Aas Mortensen, 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.

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 Type : Interventional  (Clinical Trial)
Estimated Enrollment : 170 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 : February 2013
Estimated Primary Completion Date : September 2017
Estimated Study Completion Date : September 2017

Resource links provided by the National Library of Medicine

U.S. FDA Resources

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

Primary Outcome Measures :
  1. Improved Cr EDTA clearance [ Time Frame: 0, 1 year, 2 years ]

Secondary Outcome Measures :
  1. Reduced urine protein levels [ Time Frame: Every 3 months ]
  2. Reduced fibrosis [ Time Frame: 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.

  3. Reduced blood pressure [ Time Frame: 0, 1 year, 2 years ]
  4. Cardiovascular events [ Time Frame: 2 years ]

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01602861

Odense University Hospital
Odense C, Denmark, 5000
Sponsors and Collaborators
Odense University Hospital
Fredericia Hosptial
Study Director: Claus Bistrup, MD, ph.d. Dep. of Nephrology, Odense University Hospital

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
First Posted: May 21, 2012    Key Record Dates
Last Update Posted: January 24, 2014
Last Verified: January 2014

Keywords provided by Line Aas Mortensen, Odense University Hospital:
calcineurin inhibitor
kidney transplant
chronic rejection

Additional relevant MeSH terms:
Calcineurin Inhibitors
Mineralocorticoid Receptor Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Diuretics, Potassium Sparing
Natriuretic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action