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| Name | Class |
|---|---|
| University of Helsinki | OTHER |
| Academy of Finland | OTHER |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Simvastatin 80 mg group | Active Comparator | The transplant recipients who have received an organ from donors treated with simvastatin 80 mg. |
|
| Control Rx | Experimental | The transplant recipients who have received an organ from non-treated donors. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Simvastatin 80mg | Drug | The transplant recipients who have received an organ from donors treated with simvastatin 80 mg. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 | 1-24 hour |
| Measure | Description | Time Frame |
|---|---|---|
| Postoperative hemodynamics | Arterial line and pulmonary artery catheter measurements 6, 12, 24, 48, and 72 hours | 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 |
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Inclusion criteria for a donor:
Exclusion Criteria for the heart/lung donor:
Inclusion criteria for a transplant recipient:
Exclusive Criteria for the recipient
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| Name | Affiliation | Role |
|---|---|---|
| Karl B Lemstrom, MD, PhD | Cardiac surgery, Heart and Lung Center, Helsinki University Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Cardiac Surgery, Heart and Lung Center, Helsinki University Hospital | Helsinki | FI-00029 | Finland |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 31352795 | Derived | 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. |
| Label | URL |
|---|---|
| Website of Heart and Lung Center, Helsinki University Hospital | View source |
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| ID | Term |
|---|---|
| D006333 | Heart Failure |
| D012131 | Respiratory Insufficiency |
| D017093 | Liver Failure |
| D051437 | Renal Insufficiency |
| D015427 | Reperfusion Injury |
| D012059 | Rejection, Psychology |
| ID | Term |
|---|---|
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D012120 | Respiration Disorders |
| D012140 | Respiratory Tract Diseases |
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| ID | Term |
|---|---|
| D019821 | Simvastatin |
| D014002 | Tin Fluorides |
| ID | Term |
|---|---|
| D008148 | Lovastatin |
| D009281 | Naphthalenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
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| Control Rx | Drug | The transplant recipients who have received an organ from non-treated donors. |
|
| 0-72h |
| Heart transplant function | Heart transplant function analyzed by P-ProBNP and echocardiogram | 0-20 years |
| Cardiac allograft vasculopathy | Cardiac allograft vasculopathy analyzed coronary angiogram | at 1, 3, and 5 years |
| Biopsy proven acute rejection | Grade of rejection at endomyocardial biopsy | 0-20 years |
| Rejection treatments | Any rejection treatments | 0-20 years |
| Short- and long-term survival | Time to all-cause mortality | 0-20 years |
| Substudy 1 | Outcome of kidney transplant recipients | 0-20 years |
| Substudy 2 | Outcome of liver transplant recipients | 0-20 years |
| Substudy 3 | Outcome of lung transplant recipients | 0-20 years |
| Substudy 4 | Development of biomarkers for ischemia-reperfusion injury after heart transplantation | 0-24 h |
| Substudy 5 | Development of molecular profiling for endomyocardial biopsy after heart transplantation | 0-1 years |
| Substudy 6 | Effect of donor and recipient genomic backgroud on long term outcomes after heart transplantation | 0-20 years |
| Substudy 7 | Effect of donor and recipient genomic backgroud on long term outcomes after kidney transplantation | 0-20 years |
| Website of Transplantation Laboratory, University of Helsinki | View source |
| D048550 | Hepatic Insufficiency |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D014652 | Vascular Diseases |
| D011183 | Postoperative Complications |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D012919 | Social Behavior |
| D001519 | Behavior |
| D006844 |
| Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D011083 | Polycyclic Compounds |
| D005459 | Fluorides |
| D006858 | Hydrofluoric Acid |
| D017611 | Fluorine Compounds |
| D007287 | Inorganic Chemicals |
| D017971 | Tin Compounds |
| D002327 | Cariostatic Agents |
| D001697 | Biomedical and Dental Materials |
| D008420 | Manufactured Materials |
| D013676 | Technology, Industry, and Agriculture |