Donor Simvastatin Treatment in Organ Transplantation (SIMVA)

The aim of the study is to investigate the effects of donor simvastatin treatment on ischemia-reperfusion injury after heart transplantation.

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.

Recipient plasma release of cardiac troponins and creatinine kinase-MB and P-lactate, S-hs-CRP, peripheral blood leukocytes and neutrophils after heart transplantation

Postoperative use of inotropes and hemodynamic support at 6, 12, 24, 48, and 72 hours and the length of inotropic support

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

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.