Disorder Related to Renal TransplantationPhase 4SPIRENNCT01602861
The Effects of Spironolactone on Calcineurin Inhibitor Induced Nephrotoxicity
A Phase 4 study testing Spironolactone in people with Disorder Related to Renal Transplantation, run by Odense University Hospital at 1 site in Denmark.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Disorder Related to Renal Transplantation
- What is being tested?
- Spironolactone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 188 participants
- Where
- 1 siteDenmark
- Study dates
- Feb 2013to Apr 2021
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age > 18 years
- Proteinuria < 3 g/24 hours
- Creatinine clearance ≥ 30 mL/min
- S-Potassium < 5,5 mmol/L
- Negative pregnancy test at the inclusion and anticonception
Who cannot join
- Intolerance to spironolactone
- Creatinine clearance < 30 ml/min
- S-Potassium ≥ 5,5 mmol/L
- Resin or digoxine treatment
- Pregnancy or planned pregnancy
- Relevant organic, systemic or mental illness
- Anticipation of lack of compliance or understanding the study
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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.
- Being tested
- Spironolactone, placebo
- Keywords
- Fibrosis, calcineurin inhibitor, kidney transplant, chronic rejection
- Medical subject headings
- Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SpironolactoneDrug
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).
placeboDrug
| Study group | Role | What they receive |
|---|---|---|
| Spironolactone | Experimental | Not described Receives: Drug: Spironolactone |
| Placebo | Placebo comparator | Not described Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Cr EDTA clearance
Measured: 0, 1 year, 2 years, 3 years
Secondary outcomes (4)
Reduced urine protein levels (change from baseline)
Measured: 0, 1 year, 2 years, 3 years
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.
Measured: 0, 2 years
Reduced blood pressure (change from baseline)
Measured: 0, 1 year, 2 years, 3 years
Cardiovascular events
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 May 2012 (estimated)
- Study startFeb 2013
- Primary completionApr 2021
- Study completionApr 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Disorder Related to Renal TransplantationStudies of the same condition, open and under way.
- More trials run by Odense University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 188 participants (actual)
Sponsor and investigators
- Lead sponsor
- Odense University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Fredericia Hosptial
- Responsible party
- Principal investigator, Line Aas Mortensen, Odense University Hospital
- Investigators
- Claus Bistrup, MD, ph.d., Study director, Dep. of Nephrology, Odense University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01602861
- Sponsor's protocol ID
- Eudra CT: 2011-002243-98
- Acronym
- SPIREN
- Status last verified
- Sep 2021
- First submitted
- 17 May 2012
- Last updated
- 9 Sep 2021
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Natale P, Mooi PK, Palmer SC, Cross NB, Cooper TE, Webster AC, Masson P, Craig JC, Strippoli GF. Antihypertensive treatment for kidney transplant recipients. Cochrane Database Syst Rev. 2024 Jul 31;7(7):CD003598. doi: 10.1002/14651858.CD003598.pub3.
PubMed 39082471Mortensen 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.
PubMed 29724188
Study at a glance
From the registry record, last updated by the sponsor on 9 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effects of Spironolactone on Calcineurin Inhibitor Induced Nephrotoxicity
- ClinicalTrials.gov ID
- NCT01602861
- Acronym / sponsor ID
- SPIREN / Eudra CT: 2011-002243-98
- Keywords
- Fibrosis, calcineurin inhibitor, kidney transplant, chronic rejection
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 188 participants (actual)
- Lead sponsor
- Odense University HospitalUniversity, hospital or other
- Collaborators
- Fredericia Hosptial
- Study start
- Feb 2013
- Primary completion
- Apr 2021 (actual)
- Study completion
- Apr 2021 (actual)
- First posted
- 21 May 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Spironolactone | Experimental | Drug: Spironolactone |
| Placebo | Placebo comparator | Drug: placebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Age > 18 years
- Proteinuria < 3 g/24 hours
- Creatinine clearance ≥ 30 mL/min
- S-Potassium < 5,5 mmol/L
- Negative pregnancy test at the inclusion and anticonception
Key exclusion criteria (7 listed)
- Intolerance to spironolactone
- Creatinine clearance < 30 ml/min
- S-Potassium ≥ 5,5 mmol/L
- Resin or digoxine treatment
- Pregnancy or planned pregnancy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SpironolactoneOne 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). | Drug | Spironolactone |
| placebo | Drug | Placebo |
Primary outcome
Change in Cr EDTA clearance
Time frame: 0, 1 year, 2 years, 3 years
4 secondary outcomes
Reduced urine protein levels (change from baseline)
Time frame: 0, 1 year, 2 years, 3 years
Reduced fibrosis (change from baseline)
Time frame: 0, 2 years
Reduced blood pressure (change from baseline)
Time frame: 0, 1 year, 2 years, 3 years
Cardiovascular events
Time frame: 3 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Sep 2021.
- Derived from this study: PubMed 39082471Natale P, Mooi PK, Palmer SC, Cross NB, Cooper TE, Webster AC, Masson P, Craig JC, Strippoli GF. Antihypertensive treatment for kidney transplant recipients. Cochrane Database Syst Rev. 2024 Jul 31;7(7):CD003598. doi: 10.1002/14651858.CD003598.pub3.
- Derived from this study: PubMed 29724188Mortensen 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Claus Bistrup, MD, ph.d. study director
Dep. of Nephrology, Odense University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Spironolactone in people with Disorder Related to Renal Transplantation, run by Odense University Hospital at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Cr EDTA clearance (time frame: 0, 1 year, 2 years, 3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01602861, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Sep 2021.