Donor Simvastatin Treatment in Organ Transplantation

Heart Failure Clinical Trial

— SIMVA  

Official title:

Donor Simvastatin Treatment in Organ Transplantation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01160978
• Other study ID #: T1020SIMVASTATIN
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: July 12, 2010
• Last updated: September 17, 2017
• Start date: June 1, 2010
• Est. completion date: August 1, 2016

Study information

• Verified date: September 2017
• Source: Helsinki University Central Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 84
• Est. completion date: August 1, 2016
• Est. primary completion date: August 1, 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Heart Failure
• Kidney Failure
• Liver Failure
• Renal Insufficiency
• Respiratory Failure
• Respiratory Insufficiency
• Transplantation

Intervention

Drug:
• Simvastatin 80mg
The transplant recipients who have received an organ from donors treated with simvastatin 80 mg.
• Control Rx
The transplant recipients who have received an organ from non-treated donors.

Locations

Country	Name	City	State
Finland	Cardiac Surgery, Heart and Lung Center, Helsinki University Hospital	Helsinki

Sponsors (3)

Lead Sponsor	Collaborator
Helsinki University Central Hospital	Academy of Finland, Helsinki University

Country where clinical trial is conducted

Finland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Secondary	Postoperative hemodynamics	Arterial line and pulmonary artery catheter measurements 6, 12, 24, 48, and 72 hours	0-72h
Secondary	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	0-72h
Secondary	Heart transplant function	Heart transplant function analyzed by P-ProBNP and echocardiogram	0-20 years
Secondary	Cardiac allograft vasculopathy	Cardiac allograft vasculopathy analyzed coronary angiogram	at 1, 3, and 5 years
Secondary	Biopsy proven acute rejection	Grade of rejection at endomyocardial biopsy	0-20 years
Secondary	Rejection treatments	Any rejection treatments	0-20 years
Secondary	Short- and long-term survival	Time to all-cause mortality	0-20 years
Secondary	Substudy 1	Outcome of kidney transplant recipients	0-20 years
Secondary	Substudy 2	Outcome of liver transplant recipients	0-20 years
Secondary	Substudy 3	Outcome of lung transplant recipients	0-20 years
Secondary	Substudy 4	Development of biomarkers for ischemia-reperfusion injury after heart transplantation	0-24 h
Secondary	Substudy 5	Development of molecular profiling for endomyocardial biopsy after heart transplantation	0-1 years
Secondary	Substudy 6	Effect of donor and recipient genomic backgroud on long term outcomes after heart transplantation	0-20 years
Secondary	Substudy 7	Effect of donor and recipient genomic backgroud on long term outcomes after kidney transplantation	0-20 years

External Links

•   Website of Heart and Lung Center, Helsinki University Hospital
•   Website of Transplantation Laboratory, University of Helsinki