Clinical trial NCT01160978: Donor Simvastatin Treatment in Organ Transplantation
Official title: Donor Simvastatin Treatment in Organ Transplantation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Heart Failure
Respiratory Failure
Liver Failure
Kidney Failure
Transplantation
Keywords: Transplantation
Simvastatin treatment
Ischemia-reperfusion injury
Rejection
Lead sponsor: Helsinki University Central Hospital
Sponsor class: OTHER
Collaborators: name: University of Helsinki
name: Academy of Finland
First posted: 2010-07-13
Enrollment: 84
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Donor treatment with simvastatin reduces ischemia-reperfusion injury after heart transplantation
timeFrame: 1-24 hour
Secondary outcomes:
measure: Postoperative hemodynamics
timeFrame: 0-72h
measure: Postoperative use of inotropes and hemodynamic support
timeFrame: 0-72h
measure: Heart transplant function
timeFrame: 0-20 years
measure: Cardiac allograft vasculopathy
timeFrame: at 1, 3, and 5 years
measure: Biopsy proven acute rejection
timeFrame: 0-20 years
measure: Rejection treatments
timeFrame: 0-20 years
measure: Short- and long-term survival
timeFrame: 0-20 years
measure: Substudy 1
timeFrame: 0-20 years
measure: Substudy 2
timeFrame: 0-20 years
measure: Substudy 3
timeFrame: 0-20 years
measure: Substudy 4
timeFrame: 0-24 h
measure: Substudy 5
timeFrame: 0-1 years
measure: Substudy 6
timeFrame: 0-20 years
measure: Substudy 7
timeFrame: 0-20 years
Other outcomes:
Locations:
city: Helsinki
country: Finland
facility: Cardiac Surgery, Heart and Lung Center, Helsinki University Hospital
Study officials:
affiliation: Cardiac surgery, Heart and Lung Center, Helsinki University Hospital
name: Karl B Lemstrom, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.