Donor Simvastatin Treatment in Organ Transplantation (SIMVA)

Helsinki University Central Hospital (HUCH)

Status and phase: Completed; Phase 3; Phase 2

Conditions: Kidney Failure; Respiratory Failure; Liver Failure; Heart Failure; Transplantation

Treatments: Drug: Simvastatin 80mg; Drug: Control Rx

Study type: Interventional

Funder types: Other

Identifiers

NCT01160978

T1020SIMVASTATIN

Details and patient eligibility

About

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

Full 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.

Enrollment: 84 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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84 participants in 2 patient groups

Simvastatin 80 mg group

Active Comparator group

Description:

The transplant recipients who have received an organ from donors treated with simvastatin 80 mg.

Treatment:

Drug: Simvastatin 80mg

Control Rx

Experimental group

Description:

The transplant recipients who have received an organ from non-treated donors.

Treatment:

Drug: Control Rx