Donor Simvastatin Treatment in Organ Transplantation (SIMVA)
Primary Purpose
Heart Failure, Respiratory Failure, Liver Failure
Status
Completed
Phase
Phase 2
Locations
Finland
Study Type
Interventional
Intervention
Simvastatin 80mg
Control Rx
Sponsored by
About this trial
This is an interventional treatment trial for Heart Failure focused on measuring Transplantation, Simvastatin treatment, Ischemia-reperfusion injury, Rejection
Eligibility Criteria
Inclusion criteria for a donor:
- 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
Exclusion Criteria for the heart/lung donor:
- 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
Inclusion criteria for a transplant recipient:
- 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
Sites / Locations
- Cardiac Surgery, Heart and Lung Center, Helsinki University Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Experimental
Arm Label
Simvastatin 80 mg group
Control Rx
Arm Description
The transplant recipients who have received an organ from donors treated with simvastatin 80 mg.
The transplant recipients who have received an organ from non-treated donors.
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
Postoperative hemodynamics
Arterial line and pulmonary artery catheter measurements 6, 12, 24, 48, and 72 hours
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
Heart transplant function
Heart transplant function analyzed by P-ProBNP and echocardiogram
Cardiac allograft vasculopathy
Cardiac allograft vasculopathy analyzed coronary angiogram
Biopsy proven acute rejection
Grade of rejection at endomyocardial biopsy
Rejection treatments
Any rejection treatments
Short- and long-term survival
Time to all-cause mortality
Substudy 1
Outcome of kidney transplant recipients
Substudy 2
Outcome of liver transplant recipients
Substudy 3
Outcome of lung transplant recipients
Substudy 4
Development of biomarkers for ischemia-reperfusion injury after heart transplantation
Substudy 5
Development of molecular profiling for endomyocardial biopsy after heart transplantation
Substudy 6
Effect of donor and recipient genomic backgroud on long term outcomes after heart transplantation
Substudy 7
Effect of donor and recipient genomic backgroud on long term outcomes after kidney transplantation
Full Information
NCT ID
NCT01160978
First Posted
July 12, 2010
Last Updated
September 17, 2017
Sponsor
Helsinki University Central Hospital
Collaborators
University of Helsinki, Academy of Finland
1. Study Identification
Unique Protocol Identification Number
NCT01160978
Brief Title
Donor Simvastatin Treatment in Organ Transplantation
Acronym
SIMVA
Official Title
Donor Simvastatin Treatment in Organ Transplantation
Study Type
Interventional
2. Study Status
Record Verification Date
September 2017
Overall Recruitment Status
Completed
Study Start Date
June 1, 2010 (Actual)
Primary Completion Date
August 1, 2016 (Actual)
Study Completion Date
August 1, 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Helsinki University Central Hospital
Collaborators
University of Helsinki, Academy of Finland
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Heart Failure, Respiratory Failure, Liver Failure, Kidney Failure, Transplantation
Keywords
Transplantation, Simvastatin treatment, Ischemia-reperfusion injury, Rejection
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
84 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Simvastatin 80 mg group
Arm Type
Active Comparator
Arm Description
The transplant recipients who have received an organ from donors treated with simvastatin 80 mg.
Arm Title
Control Rx
Arm Type
Experimental
Arm Description
The transplant recipients who have received an organ from non-treated donors.
Intervention Type
Drug
Intervention Name(s)
Simvastatin 80mg
Other Intervention Name(s)
simvastatin
Intervention Description
The transplant recipients who have received an organ from donors treated with simvastatin 80 mg.
Intervention Type
Drug
Intervention Name(s)
Control Rx
Intervention Description
The transplant recipients who have received an organ from non-treated donors.
Primary Outcome Measure Information:
Title
Donor treatment with simvastatin reduces ischemia-reperfusion injury after heart transplantation
Description
Recipient plasma release of cardiac troponins and creatinine kinase-MB and P-lactate, S-hs-CRP, peripheral blood leukocytes and neutrophils after heart transplantation
Time Frame
1-24 hour
Secondary Outcome Measure Information:
Title
Postoperative hemodynamics
Description
Arterial line and pulmonary artery catheter measurements 6, 12, 24, 48, and 72 hours
Time Frame
0-72h
Title
Postoperative use of inotropes and hemodynamic support
Description
Postoperative use of inotropes and hemodynamic support at 6, 12, 24, 48, and 72 hours and the length of inotropic support
Time Frame
0-72h
Title
Heart transplant function
Description
Heart transplant function analyzed by P-ProBNP and echocardiogram
Time Frame
0-20 years
Title
Cardiac allograft vasculopathy
Description
Cardiac allograft vasculopathy analyzed coronary angiogram
Time Frame
at 1, 3, and 5 years
Title
Biopsy proven acute rejection
Description
Grade of rejection at endomyocardial biopsy
Time Frame
0-20 years
Title
Rejection treatments
Description
Any rejection treatments
Time Frame
0-20 years
Title
Short- and long-term survival
Description
Time to all-cause mortality
Time Frame
0-20 years
Title
Substudy 1
Description
Outcome of kidney transplant recipients
Time Frame
0-20 years
Title
Substudy 2
Description
Outcome of liver transplant recipients
Time Frame
0-20 years
Title
Substudy 3
Description
Outcome of lung transplant recipients
Time Frame
0-20 years
Title
Substudy 4
Description
Development of biomarkers for ischemia-reperfusion injury after heart transplantation
Time Frame
0-24 h
Title
Substudy 5
Description
Development of molecular profiling for endomyocardial biopsy after heart transplantation
Time Frame
0-1 years
Title
Substudy 6
Description
Effect of donor and recipient genomic backgroud on long term outcomes after heart transplantation
Time Frame
0-20 years
Title
Substudy 7
Description
Effect of donor and recipient genomic backgroud on long term outcomes after kidney transplantation
Time Frame
0-20 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion criteria for a donor:
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
Exclusion Criteria for the heart/lung donor:
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
Inclusion criteria for a transplant recipient:
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Karl B Lemstrom, MD, PhD
Organizational Affiliation
Cardiac surgery, Heart and Lung Center, Helsinki University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Cardiac Surgery, Heart and Lung Center, Helsinki University Hospital
City
Helsinki
ZIP/Postal Code
FI-00029
Country
Finland
12. IPD Sharing Statement
Citations:
PubMed Identifier
31352795
Citation
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.
Results Reference
derived
Links:
URL
http://www.hus.fi/sydanjakeuhkokeskus
Description
Website of Heart and Lung Center, Helsinki University Hospital
URL
https://www.helsinki.fi/en/researchgroups/transplantation-laboratory
Description
Website of Transplantation Laboratory, University of Helsinki
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Donor Simvastatin Treatment in Organ Transplantation
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