Donor Simvastatin Treatment in Organ Transplantation
- Conditions
- Respiratory FailureHeart FailureKidney FailureLiver FailureTransplantation
- Interventions
- Drug: Control Rx
- Registration Number
- NCT01160978
- Lead Sponsor
- Helsinki University Central Hospital
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 84
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Simvastatin 80 mg group Simvastatin 80mg The transplant recipients who have received an organ from donors treated with simvastatin 80 mg. Control Rx Control Rx The transplant recipients who have received an organ from non-treated donors.
- Primary Outcome Measures
Name Time Method Donor treatment with simvastatin reduces ischemia-reperfusion injury after heart transplantation 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
- Secondary Outcome Measures
Name Time Method Postoperative hemodynamics 0-72h Arterial line and pulmonary artery catheter measurements 6, 12, 24, 48, and 72 hours
Postoperative use of inotropes and hemodynamic support 0-72h Postoperative use of inotropes and hemodynamic support at 6, 12, 24, 48, and 72 hours and the length of inotropic support
Heart transplant function 0-20 years Heart transplant function analyzed by P-ProBNP and echocardiogram
Cardiac allograft vasculopathy at 1, 3, and 5 years Cardiac allograft vasculopathy analyzed coronary angiogram
Biopsy proven acute rejection 0-20 years Grade of rejection at endomyocardial biopsy
Substudy 6 0-20 years Effect of donor and recipient genomic backgroud on long term outcomes after heart transplantation
Substudy 7 0-20 years Effect of donor and recipient genomic backgroud on long term outcomes after kidney transplantation
Rejection treatments 0-20 years Any rejection treatments
Short- and long-term survival 0-20 years Time to all-cause mortality
Substudy 1 0-20 years Outcome of kidney transplant recipients
Substudy 2 0-20 years Outcome of liver transplant recipients
Substudy 3 0-20 years Outcome of lung transplant recipients
Substudy 4 0-24 h Development of biomarkers for ischemia-reperfusion injury after heart transplantation
Substudy 5 0-1 years Development of molecular profiling for endomyocardial biopsy after heart transplantation
Trial Locations
- Locations (1)
Cardiac Surgery, Heart and Lung Center, Helsinki University Hospital
🇫🇮Helsinki, Finland