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Donor Simvastatin Treatment in Organ Transplantation (SIMVA)

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01160978
First Posted: July 13, 2010
Last Update Posted: September 19, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborators:
Helsinki University
Academy of Finland
Information provided by (Responsible Party):
Karl Lemstrom, Helsinki University Central Hospital
  Purpose
The aim of the study is to investigate the effects of donor simvastatin treatment on ischemia-reperfusion injury after heart transplantation.

Condition Intervention Phase
Heart Failure Respiratory Failure Liver Failure Kidney Failure Transplantation Drug: Simvastatin 80mg Drug: Control Rx Phase 2 Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Donor Simvastatin Treatment in Organ Transplantation

Resource links provided by NLM:


Further study details as provided by Karl Lemstrom, Helsinki University Central Hospital:

Primary Outcome Measures:
  • Donor treatment with simvastatin reduces ischemia-reperfusion injury after heart transplantation [ Time Frame: 1-24 hour ]
    Recipient plasma release of cardiac troponins and creatinine kinase-MB and P-lactate, S-hs-CRP, peripheral blood leukocytes and neutrophils after heart transplantation


Secondary Outcome Measures:
  • Postoperative hemodynamics [ Time Frame: 0-72h ]
    Arterial line and pulmonary artery catheter measurements 6, 12, 24, 48, and 72 hours

  • Postoperative use of inotropes and hemodynamic support [ Time Frame: 0-72h ]
    Postoperative use of inotropes and hemodynamic support at 6, 12, 24, 48, and 72 hours and the length of inotropic support

  • Heart transplant function [ Time Frame: 0-20 years ]
    Heart transplant function analyzed by P-ProBNP and echocardiogram

  • Cardiac allograft vasculopathy [ Time Frame: at 1, 3, and 5 years ]
    Cardiac allograft vasculopathy analyzed coronary angiogram

  • Biopsy proven acute rejection [ Time Frame: 0-20 years ]
    Grade of rejection at endomyocardial biopsy

  • Rejection treatments [ Time Frame: 0-20 years ]
    Any rejection treatments

  • Short- and long-term survival [ Time Frame: 0-20 years ]
    Time to all-cause mortality

  • Substudy 1 [ Time Frame: 0-20 years ]
    Outcome of kidney transplant recipients

  • Substudy 2 [ Time Frame: 0-20 years ]
    Outcome of liver transplant recipients

  • Substudy 3 [ Time Frame: 0-20 years ]
    Outcome of lung transplant recipients

  • Substudy 4 [ Time Frame: 0-24 h ]
    Development of biomarkers for ischemia-reperfusion injury after heart transplantation

  • Substudy 5 [ Time Frame: 0-1 years ]
    Development of molecular profiling for endomyocardial biopsy after heart transplantation

  • Substudy 6 [ Time Frame: 0-20 years ]
    Effect of donor and recipient genomic backgroud on long term outcomes after heart transplantation

  • Substudy 7 [ Time Frame: 0-20 years ]
    Effect of donor and recipient genomic backgroud on long term outcomes after kidney transplantation


Enrollment: 84
Actual Study Start Date: June 1, 2010
Study Completion Date: August 1, 2016
Primary Completion Date: August 1, 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Simvastatin 80 mg group
The transplant recipients who have received an organ from donors treated with simvastatin 80 mg.
Drug: Simvastatin 80mg
The transplant recipients who have received an organ from donors treated with simvastatin 80 mg.
Other Name: simvastatin
Experimental: Control Rx
The transplant recipients who have received an organ from non-treated donors.
Drug: Control Rx
The transplant recipients who have received an organ from non-treated donors.

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

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 70 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01160978


Locations
Finland
Cardiac Surgery, Heart and Lung Center, Helsinki University Hospital
Helsinki, Finland, FI-00029
Sponsors and Collaborators
Helsinki University Central Hospital
Helsinki University
Academy of Finland
Investigators
Principal Investigator: Karl B Lemstrom, MD, PhD Cardiac surgery, Heart and Lung Center, Helsinki University Hospital
  More Information

Additional Information:
Responsible Party: Karl Lemstrom, Consultant Cardiothoracic Surgeon, Helsinki University Central Hospital
ClinicalTrials.gov Identifier: NCT01160978     History of Changes
Other Study ID Numbers: T1020SIMVASTATIN
First Submitted: July 12, 2010
First Posted: July 13, 2010
Last Update Posted: September 19, 2017
Last Verified: September 2017

Keywords provided by Karl Lemstrom, Helsinki University Central Hospital:
Transplantation
Simvastatin treatment
Ischemia-reperfusion injury
Rejection

Additional relevant MeSH terms:
Heart Failure
Respiratory Insufficiency
Renal Insufficiency
Liver Failure
Heart Diseases
Cardiovascular Diseases
Respiration Disorders
Respiratory Tract Diseases
Kidney Diseases
Urologic Diseases
Hepatic Insufficiency
Liver Diseases
Digestive System Diseases
Simvastatin
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors