Heart FailurePhase 2/3SIMVANCT01160978
Donor Simvastatin Treatment in Organ Transplantation
A Phase 2/3 study testing Simvastatin 80mg in people with Heart Failure and Respiratory Failure, run by Helsinki University Central Hospital at 1 site in Finland.
Trial summary
The aim of the study is to investigate the effects of donor simvastatin treatment on ischemia-reperfusion injury after heart transplantation. Read more about this study
- Who is it for?
- Ages 18 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Heart Failure, Respiratory Failure, Liver Failure
- What is being tested?
- Simvastatin 80mg
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 84 participants
- Where
- 1 siteFinland
- Study dates
- 1 Jun 2010to 1 Aug 2016
- Phase
- Phase 2/3
- 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 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Heart transplant donor
- Age 18-60 years
- Previously healthy
- No cholesterol medication
- Normal ECHO with LVEF >45%, normal right ventricle and normal coronary angiography
- PiO2/FiO2 > 40kPA, normal chest radiograph and normal bronchoscopy in lung donors
Show all 12Show fewer
- Age between 18-70 for heart transplant recipients
- Male or female
- Listed for heart, lung, kidney, or liver transplantation
- Exclusive Criteria for the recipient
- systemic sepsis
- a positive cross match
Who cannot join
- Severe left ventricular hypertrophy > 14 mm
- High dose of inotropes (dopamine or dobutamine > 20ug/kg/min or norepinephrine >0.2 ug/kg/min) at the time of procurement
- Donor outside of the study country Finland
Trial locations and contacts
1 site in 1 country.
Finland1 site
Cardiac Surgery, Heart and Lung Center, Helsinki University Hospital
Helsinki, FI-00029
About this study
The aim of the study is to investigate the effects of donor simvastatin treatment on ischemia-reperfusion injury after heart transplantation.
Read the detailed description
The study hypothesis of the single center randomized double-blinded clinical trial is that donor simvastatin treatment reduces ischemia-reperfusion injury after heart transplantation. Also, it potentially decreases natural immune activity, rejection activation and thus improves long-term prognosis.
Simvastatin is administered to heart and/or lung donors through the nasogastric tube 4-6 hours prior to organ harvesting. Control organ donors do not receive simvastatin. The randomization and donor hospital instruction of the donor simvastatin treatment is performed by the transplant coordinator. All other caregivers and the transplant recipient are blinded to the treatment group allocation.
The impact of donor simvastatin treatment is investigated and analyzed by several specific blood samples and biopsies that are taken from the recipient at the various time-points during the perioperative and postoperative phase.
In heart transplant recipients (n=42 in the donor simvastatin treatment group and n=42 in the control group), the primary end-point is postoperative cardiac enzyme serum levels (TnT, TnI, and CK-MB 1 hour, 6 hours, 12 hours and 24 hours after transplantation) and primary graft failure. Secondary end-points include peri- and postoperative parameters hemodynamics, short- and long term survival, biopsy-proven rejections, rejection treatments, and chronic rejection at 1, 5, 10, and 20 years after transplantation.
Lung, kidney and liver transplant recipients that have received organs from donors randomized to the control group or donor simvastatin group will also be followed for ischemia-reperfusion injury, perioperative organ function, innate and adaptive immunity and patient survival.
- Being tested
- Simvastatin 80mg, Control Rx
- Keywords
- Transplantation, Simvastatin treatment, Ischemia-reperfusion injury, Rejection
- Medical subject headings
- Heart Failure, Respiratory Insufficiency, Liver Failure, Renal Insufficiency, Reperfusion Injury, Rejection, Psychology
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Simvastatin 80mgDrug
Also called simvastatin
The transplant recipients who have received an organ from donors treated with simvastatin 80 mg.
Control RxDrug
The transplant recipients who have received an organ from non-treated donors.
| Study group | Role | What they receive |
|---|---|---|
| Simvastatin 80 mg group | Active comparator | The transplant recipients who have received an organ from donors treated with simvastatin 80 mg. Receives: Drug: Simvastatin 80mg |
| Control Rx | Experimental | The transplant recipients who have received an organ from non-treated donors. Receives: Drug: Control Rx |
What is being measured
The primary outcome is the main question the study is designed to answer.
Donor treatment with simvastatin reduces ischemia-reperfusion injury after heart transplantation
Recipient plasma release of cardiac troponins and creatinine kinase-MB and P-lactate, S-hs-CRP, peripheral blood leukocytes and neutrophils after heart transplantation
Measured: 1-24 hour
Secondary outcomes (14)
Postoperative hemodynamics
Arterial line and pulmonary artery catheter measurements 6, 12, 24, 48, and 72 hours
Measured: 0-72h
Postoperative use of inotropes and hemodynamic support
Postoperative use of inotropes and hemodynamic support at 6, 12, 24, 48, and 72 hours and the length of inotropic support
Measured: 0-72h
Heart transplant function
Heart transplant function analyzed by P-ProBNP and echocardiogram
Measured: 0-20 years
Cardiac allograft vasculopathy
Cardiac allograft vasculopathy analyzed coronary angiogram
Measured: at 1, 3, and 5 years
Biopsy proven acute rejection
Grade of rejection at endomyocardial biopsy
Measured: 0-20 years
Rejection treatments
Any rejection treatments
Measured: 0-20 years
Short- and long-term survival
Time to all-cause mortality
Measured: 0-20 years
Substudy 1
Outcome of kidney transplant recipients
Measured: 0-20 years
Substudy 2
Outcome of liver transplant recipients
Measured: 0-20 years
Substudy 3
Outcome of lung transplant recipients
Measured: 0-20 years
Substudy 4
Development of biomarkers for ischemia-reperfusion injury after heart transplantation
Measured: 0-24 h
Substudy 5
Development of molecular profiling for endomyocardial biopsy after heart transplantation
Measured: 0-1 years
Substudy 6
Effect of donor and recipient genomic backgroud on long term outcomes after heart transplantation
Measured: 0-20 years
Substudy 7
Effect of donor and recipient genomic backgroud on long term outcomes after kidney transplantation
Measured: 0-20 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jul 2010 (estimated)
- Study start1 Jun 2010
- Primary completion1 Aug 2016
- Study completion1 Aug 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Heart FailureStudies of the same condition, open and under way.
- More trials run by Helsinki University Central 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 84 participants (actual)
Sponsor and investigators
- Lead sponsor
- Helsinki University Central Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- University of Helsinki, Academy of Finland
- Responsible party
- Principal investigator, Karl Lemstrom, Helsinki University Central Hospital
- Investigators
- Karl B Lemstrom, MD, PhD, Principal investigator, Cardiac surgery, Heart and Lung Center, Helsinki University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01160978
- Sponsor's protocol ID
- T1020SIMVASTATIN
- Acronym
- SIMVA
- Status last verified
- Sep 2017
- First submitted
- 12 Jul 2010
- Last updated
- 19 Sep 2017
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Nykanen AI, Holmstrom EJ, Tuuminen R, Krebs R, Dhaygude K, Kankainen M, Jokinen JJ, Lommi J, Helantera I, Raisanen-Sokolowski A, Syrjala SO, Lemstrom KB. Donor Simvastatin Treatment in Heart Transplantation. Circulation. 2019 Aug 20;140(8):627-640. doi: 10.1161/CIRCULATIONAHA.119.039932. Epub 2019 Jul 29.
PubMed 31352795
Study at a glance
From the registry record, last updated by the sponsor on 19 Sep 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Donor Simvastatin Treatment in Organ Transplantation
- ClinicalTrials.gov ID
- NCT01160978
- Acronym / sponsor ID
- SIMVA / T1020SIMVASTATIN
- Keywords
- Transplantation, Simvastatin treatment, Ischemia-reperfusion injury, Rejection
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 84 participants (actual)
- Lead sponsor
- Helsinki University Central HospitalUniversity, hospital or other
- Collaborators
- University of Helsinki, Academy of Finland
- Study start
- 1 Jun 2010 (actual)
- Primary completion
- 1 Aug 2016 (actual)
- Study completion
- 1 Aug 2016 (actual)
- First posted
- 13 Jul 2010 (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 aim of the study is to investigate the effects of donor simvastatin treatment on ischemia-reperfusion injury after heart transplantation.
Detailed description
The study hypothesis of the single center randomized double-blinded clinical trial is that donor simvastatin treatment reduces ischemia-reperfusion injury after heart transplantation. Also, it potentially decreases natural immune activity, rejection activation and thus improves long-term prognosis.
Simvastatin is administered to heart and/or lung donors through the nasogastric tube 4-6 hours prior to organ harvesting. Control organ donors do not receive simvastatin. The randomization and donor hospital instruction of the donor simvastatin treatment is performed by the transplant coordinator. All other caregivers and the transplant recipient are blinded to the treatment group allocation.
The impact of donor simvastatin treatment is investigated and analyzed by several specific blood samples and biopsies that are taken from the recipient at the various time-points during the perioperative and postoperative phase.
In heart transplant recipients (n=42 in the donor simvastatin treatment group and n=42 in the control group), the primary end-point is postoperative cardiac enzyme serum levels (TnT, TnI, and CK-MB 1 hour, 6 hours, 12 hours and 24 hours after transplantation) and primary graft failure. Secondary end-points include peri- and postoperative parameters hemodynamics, short- and long term survival, biopsy-proven rejections, rejection treatments, and chronic rejection at 1, 5, 10, and 20 years after transplantation.
Lung, kidney and liver transplant recipients that have received organs from donors randomized to the control group or donor simvastatin group will also be followed for ischemia-reperfusion injury, perioperative organ function, innate and adaptive immunity and patient survival.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Simvastatin 80 mg group | Active comparator | Drug: Simvastatin 80mgThe transplant recipients who have received an organ from donors treated with simvastatin 80 mg. |
| Control Rx | Experimental | Drug: Control RxThe transplant recipients who have received an organ from non-treated donors. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Heart transplant donor
- Age 18-60 years
- Previously healthy
- No cholesterol medication
- Normal ECHO with LVEF >45%, normal right ventricle and normal coronary angiography
Key exclusion criteria (3 listed)
- Severe left ventricular hypertrophy > 14 mm
- High dose of inotropes (dopamine or dobutamine > 20ug/kg/min or norepinephrine >0.2 ug/kg/min) at the time of procurement
- Donor outside of the study country Finland
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 |
|---|---|---|
| Simvastatin 80mgAlso: simvastatinThe transplant recipients who have received an organ from donors treated with simvastatin 80 mg. | Drug | Simvastatin 80 mg group |
| Control RxThe transplant recipients who have received an organ from non-treated donors. | Drug | Control Rx |
Primary outcome
Donor treatment with simvastatin reduces ischemia-reperfusion injury after heart transplantation
Time frame: 1-24 hour
Recipient plasma release of cardiac troponins and creatinine kinase-MB and P-lactate, S-hs-CRP, peripheral blood leukocytes and neutrophils after heart transplantation
14 secondary outcomes
Postoperative hemodynamics
Time frame: 0-72h
Postoperative use of inotropes and hemodynamic support
Time frame: 0-72h
Heart transplant function
Time frame: 0-20 years
Cardiac allograft vasculopathy
Time frame: at 1, 3, and 5 years
Biopsy proven acute rejection
Time frame: 0-20 years
Rejection treatments
Time frame: 0-20 years
Short- and long-term survival
Time frame: 0-20 years
Substudy 1
Time frame: 0-20 years
Substudy 2
Time frame: 0-20 years
Substudy 3
Time frame: 0-20 years
Substudy 4
Time frame: 0-24 h
Substudy 5
Time frame: 0-1 years
Substudy 6
Time frame: 0-20 years
Substudy 7
Time frame: 0-20 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 19 Sep 2017.
- Derived from this study: PubMed 31352795Nykanen AI, Holmstrom EJ, Tuuminen R, Krebs R, Dhaygude K, Kankainen M, Jokinen JJ, Lommi J, Helantera I, Raisanen-Sokolowski A, Syrjala SO, Lemstrom KB. Donor Simvastatin Treatment in Heart Transplantation. Circulation. 2019 Aug 20;140(8):627-640. doi: 10.1161/CIRCULATIONAHA.119.039932. Epub 2019 Jul 29.
- Website of Heart and Lung Center, Helsinki University HospitalLink provided by the sponsor.
- Website of Transplantation Laboratory, University of HelsinkiLink provided by the sponsor.
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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.
Karl B Lemstrom, MD, PhD principal investigator
Cardiac surgery, Heart and Lung Center, Helsinki 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 2/3 study testing Simvastatin 80mg in people with Heart Failure and Respiratory Failure, run by Helsinki University Central Hospital at 1 site in Finland.
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 12 inclusion and 3 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 19 Sep 2017. 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 Finland. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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?
Donor treatment with simvastatin reduces ischemia-reperfusion injury after heart transplantation (time frame: 1-24 hour). 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 NCT01160978, which also lists 1 linked publication.
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 19 Sep 2017.