Heart Failure, Respiratory Failure, Liver Failure, Kidney Failure, Transplantation
Conditions
Keywords
Transplantation, Simvastatin treatment, Ischemia-reperfusion injury, Rejection
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.
Interventions
DRUGSimvastatin 80mg
The transplant recipients who have received an organ from donors treated with simvastatin 80 mg.
DRUGControl Rx
The transplant recipients who have received an organ from non-treated donors.
Sponsors
University of Helsinki
Academy of Finland
Helsinki University Central Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| Rejection treatments | 0-20 years | Any rejection treatments |
| Short- and long-term survival | 0-20 years | Time to all-cause mortality |
| Postoperative hemodynamics | 0-72h | Arterial line and pulmonary artery catheter measurements 6, 12, 24, 48, and 72 hours |
| 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 |
| 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 |
| Substudy 1 | 0-20 years | Outcome of kidney transplant recipients |
Countries
Finland
Outcome results
None listed