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出境医 / 临床实验 / Non-ischemic Preservation of the Donor Heart in Heart Transplantation

Non-ischemic Preservation of the Donor Heart in Heart Transplantation

Study Description
Brief Summary:
The study intends to compare standard ischemic cold static storage (ICSS) of retrieved hearts intended to be transplanted, to non-ischemic heart preservation (NIHP) in a randomized clinical multicentre trial. The primary hypothesis is that the non-ischemic hypothermic cardioplegic preservation (NIHP) is safe and superior to ischemic cold static storage (ICSS) of donor hearts. The study will investigate the safety and superiority of the new methodology in terms of improved immediate and prolonged organ function in adult heart transplanted patients.

Condition or disease Intervention/treatment Phase
Heart Transplantation Device: XVIVO heart preservation devices Device: Standard ICSS Not Applicable

Detailed Description:
This study will investigate if non-ischemic heart preservation (NIHP) with the XVIVO heart preservation devices could improve clinical outcome of patients receiving hearts after use of the technology compared to after use of standard cold ischemic preservation. This will be investigated in a European multicentre randomized controlled clinical trial. For technical reasons, blinding to the involved clinical personnel is not possible, however, biopsies will be blinded to study pathologists. The trial will include 202 recipients that have been randomized through their heart donor. The primary outcome of the study is a clinically relevant composite including graft survival, primary graft dysfunction, rejection and use of circulatory mechanical support, within 30 days and also including Cardiac Allograft Vasculopathy within 12 months. As secondary outcomes, molecular markers related to cardiac injury CKMB, ProBNP and TNI will be investigated as well as markers of the inflammatory response. Safety aspects such as effect on other organs and machine defects will also be monitored. The study population is adults, listed for heart transplantation and donors accepted as heart donors according to standard hospital procedures. Specific recipient exclusion criteria related to pre-transplant ECMO support, patients undergoing pre-transplant desensitization protocol, patients with Grown-Up Congenital Heart Disease, patients with severe kidney or liver dysfunction, patients with septicaemia, and patients diagnosed with Systemic Lupus Erythematous, sarcoidosis or amyloidosis are excluded. Cardiac death donors and donors with previous sternotomy are excluded. The study hypothesis is that NIHP better preserves the endothelium and myocyte function of the heart resulting in improved short- and medium-term recipient outcome, without inducing any new significant risks to the retrieved heart or the recipient. This is believed to be accomplished through continuous oxygenation of the heart via perfusion of the coronary arteries using an optimized preservation solution, mimicking the normal environment for the endothelium.
Study Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 202 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: Non-ischemic Preservation of the Donor Heart in Heart Transplantation - a Randomized, Controlled, Multicenter Trial
Actual Study Start Date : November 25, 2020
Estimated Primary Completion Date : January 31, 2023
Estimated Study Completion Date : December 31, 2023
Arms and Interventions
Arm Intervention/treatment
Experimental: Non-ischemic heart preservation (NIHP)
Continous cold cardioplegic perfusion of hearts
 Device: XVIVO heart preservation devices
The intervention is to preserve hearts during transportation cold, cardioplegic and non-ischemic, with a high oncotic and hormone supplemented perfusate.
Active Comparator: Ischemic cold static storage (ICSS)
Standard preservation technique
 Device: Standard ICSS
Cold static preservation using standard preservation solution
Outcome Measures
Primary Outcome Measures :
  1. 30 days mortality and 30 days graft dysfunction [ Time Frame: 30 days ]
    The Primary End-Point is defined as time-to-first-event of cardiac related death, moderate or severe primary graft dysfunction of the left ventricle or primary graft dysfunction of the right ventricle (according to Kobashigawa et al., 2014), acute cellular rejection ≥2R (according to Stewart et al., 2005) or graft failure (use of mechanical circulatory support or retransplantation) within 30 days.


Secondary Outcome Measures :
  1. 1 year mortality and 1 year graft dysfunction [ Time Frame: 1 year ]
    The key secondary endpoint is defined as time-to-first-event of either any cause of death, moderate or severe PGD-LV or PGD-RV (according to Kobashigawa et al., 2014), acute cellular rejection ≥2R (according to Stewart et al., 2005) or graft failure (use of mechanical circulatory support or retransplantation) or CAV ≥ 1 (according to Mehra, 2010) within 12 months.

  2. 30 days and 1 year mortality and graft dysfunction [ Time Frame: 30 days and 1 year ]
    The individual variables included in the composite primary endpoint at 30 days and 1 year analyzed as time-to-first-event.

  3. CKMB [ Time Frame: 3 days ]
    Creatine kinase MB (CKMB) at 6 ±2 h, 24 ±6 h, 48±6 h and 72±6 h after cross clamp removal

  4. TnI [ Time Frame: 3 days ]
    Tropinin I (TnI) at 6 ±2 h, 24 ±6 h, 48±6 h and 72±6 h after cross clamp removal

  5. ProBNP [ Time Frame: 3 days ]
    Pro Brain Natriuretic Protein (ProBNP) at 6 ±2 h, 24 ±6 h, 48±6 h and 72±6 h after cross clamp removal

  6. Stay in ICU [ Time Frame: 1 year ]
    Length of Stay at Intensive Care Unit, reported as number of days

  7. Cardiac Transplant Events [ Time Frame: 1 year ]
    Incidence of Major Adverse Cardiac Transplant Events

  8. Postoperative use of mechanical circulatory support [ Time Frame: 1 year ]
    Incidence of use of postoperative mechanical circulatory support, reported as number of days

  9. Postoperative duration of mechanical circulatory support [ Time Frame: 1 year ]
    Duration of use of postoperative mechanical circulatory support, reported as number of days

  10. Overall success/failure 30 days [ Time Frame: 30 days ]
    Success is defined as a recipient that are transplanted and alive at 30 days without any of the complication in the primary endpoint before 30 days.

  11. Overall success/failure 1 year [ Time Frame: 1 year ]
    Success is defined as a recipient that are transplanted and alive at 1 year without any of the complication given in key secondary endpoint before 1 year.

  12. ECHO data (Left ventricular ejection fraction) [ Time Frame: 24 hours ]
    ECHO data with Left ventricular ejection fraction in percentage within 24 hours after transplantation

  13. ECHO data (Left ventricular ejection fraction) [ Time Frame: 1 week ]
    ECHO data with Left ventricular ejection fraction in percentage 1 week after transplantation

  14. ECHO data (Left ventricular ejection fraction) [ Time Frame: 6 months ]
    ECHO data with Left ventricular ejection fraction in percentage 6 months after transplantation

  15. ECHO data (Left ventricular ejection fraction) [ Time Frame: 1 year ]
    ECHO data with Left ventricular ejection fraction in percentage 1 year after transplantation

  16. ECHO data (Right ventricular ejection fraction) [ Time Frame: 24 hours ]
    ECHO data with Right ventricular ejection fraction in percentage within 24 hours after transplantation

  17. ECHO data (Right ventricular ejection fraction) [ Time Frame: 1 week ]
    ECHO data with Right ventricular ejection fraction in percentage 1 week after transplantation

  18. ECHO data (Right ventricular ejection fraction) [ Time Frame: 6 months ]
    ECHO data with Right ventricular ejection fraction in percentage 6 months after transplantation

  19. ECHO data (Right ventricular ejection fraction) [ Time Frame: 1 year ]
    ECHO data with Right ventricular ejection fraction in percentage 1 year after transplantation

  20. ECHO data (Tricuspid annular plane systolic excursion) [ Time Frame: 24 hours ]
    ECHO data with Tricuspid annular plane systolic excursion (TAPSE) in mm within 24 hours after transplantation

  21. ECHO data (Tricuspid annular plane systolic excursion) [ Time Frame: 1 week ]
    ECHO data with Tricuspid annular plane systolic excursion (TAPSE) in mm 1 week after transplantation

  22. ECHO data (Tricuspid annular plane systolic excursion) [ Time Frame: 6 months ]
    ECHO data with Tricuspid annular plane systolic excursion (TAPSE) in mm 6 months after transplantation

  23. ECHO data (Tricuspid annular plane systolic excursion) [ Time Frame: 1 year ]
    ECHO data with Tricuspid annular plane systolic excursion (TAPSE) in mm 1 year after transplantation


Other Outcome Measures:
  1. Serious adverse device effects [ Time Frame: 1 year ]
    Incidence of any serious adverse device effects.

  2. Adverse device effects [ Time Frame: 1 year ]
    Incidence of any adverse device effects

  3. Device dysfunction resulting in loss of transplantable heart [ Time Frame: 12 hours ]
    Number of transplantable hearts lost due to device dysfunction

  4. Intra operative details; duration of ECC [ Time Frame: 12 hours ]
    Duration of ECC in minutes

  5. Intra operative details; duration of cross clamp [ Time Frame: 12 hours ]
    Duration of cross clamp in minutes

  6. Intra operative details; duration of surgery [ Time Frame: 12 hours ]
    Duration of surgery in minutes

  7. Intra operative details; attempts to wean off ECC [ Time Frame: 12 hours ]
    Number of attempts to wean off ECC

  8. Intra operative details; need for inotropic support [ Time Frame: 12 hours ]
    Need for inotropic support (inotropic score)

  9. Intra operative details; need for pulmonary vasodilator [ Time Frame: 12 hours ]
    Need for pulmonary vasodilator

  10. Intra operative details; defibrillations [ Time Frame: 12 hours ]
    Number of defibrillations

  11. Intra operative details; arryhythmias [ Time Frame: 12 hours ]
    Occurence of arryhythmias

  12. Intra operative details; conduction abnormalities [ Time Frame: 12 hours ]
    Number of conduction abnormalities

  13. Intra operative details; Left ventricular ejection fraction (LVEF) [ Time Frame: 12 hours ]
    LVEF in percentage

  14. Intra operative details; Right ventricular ejection fraction (RVEF) [ Time Frame: 12 hours ]
    RVEF in percentage

  15. Intra operative details; Mitral valve regurgitations [ Time Frame: 12 hours ]
    Grade of mitral valve regurgitations

  16. Intra operative details; Tricuspid valve regurgitations [ Time Frame: 12 hours ]
    Occurence of tricuspid vavle regurgitations

  17. Arterial blood gas lactate [ Time Frame: 6 hours ]
    Arterial blood gas lactate at 6 hours

  18. Arterial blood gas lactate [ Time Frame: 24 hours ]
    Arterial blood gas lactate at 24 hours

  19. Pro-BNP during follow up [ Time Frame: 1 year ]
    Pro-BNP at predefined time points during follow-up.


Eligibility Criteria
Layout table for eligibility information
Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria recipient:

  • Age ≥18 years
  • Signed informed consent form
  • Listed for heart transplantation

Inclusion criteria donor:

  • Age ≥18 and ≤70 years
  • Accepted as heart donor by the transplant team
  • (research consent from the donor if required in country)

Exclusion Criteria recipient:

  • Previous solid organ transplantation
  • Grown-up congenital heart disease (GUCH)
  • Kidney failure eGFR<40 at listing, calculated by CDK-EPI Creatinine, or ultrafiltration or dialysis or rapidly deteriorating kidney function due to a diagnosed renal disease
  • Coagulopathy due to known hepatic disease or heparin induced thrombocytopenia
  • Patient diagnosed with Systemic Lupus Erythematous, sarcoidosis or amyloidosis
  • Ongoing septicemia defined as positive blood culture (including with a durable VAD)
  • Incompatible blood group
  • Not able to understand the information provided during the informed consent procedure
  • Combined organ transplantation candidates
  • Patient already consented for another transplant related intervention study
  • Patients under pre-transplant desensitization protocol
  • Short term mechanical circulatory support pre-transplantation (Except for Intra-Aortic Balloon Pump)

Exclusion criteria donor:

  • Previous sternotomy
  • DCD hearts
Contacts and Locations

Contacts
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Contact: Marina Fredholm, M.Sc. +46 (0)73 421 42 69 marina.fredholm@xvivoperfusion.com
Contact: Andreas Wallinder, MD, PhD +46 (0)73-5192142 andreas.wallinder@xvivoperfusion.com

Locations
Layout table for location information
Belgium
UZ Leuven Recruiting
Leuven, Flemish Brabant, Belgium, 3000
Contact: Filip Rega    +3216344260    filip.rega@uzleuven.be   
France
Institut de cardiologie, Chirurgie thoracique et cardiovasculaire La Pitié Salpetrière Recruiting
Paris, Paris Cedex, France, 75651
Contact: Guillaume Lebreton    +33672320194    guillaume.lebreton@aphp.fr   
Germany
Klinikum der Universität München Not yet recruiting
München, Bavaria, Germany, 81377
Contact: Sebastian Michel    +49 89 44 00 73 468    Sebastian.michel@med.uni-muenchen.de   
Deutschen Herzzentrum Berlin Not yet recruiting
Berlin, Brandenburg, Germany, 13353
Contact: Christoph Knosalla, M.D., Ph.D.,MHBA    +49-30-4593-2087    knosalla@dhzb.de   
Italy
Azienda osedalaria di Padova Not yet recruiting
Padova, Padova PD, Italy, 35121
Contact: Gino Gerosa    +39 32 99 07 48 53    Gino.gerosa@unipd.it   
Spain
Hospital Puerto de Hierro Recruiting
Madrid, Majadahonda Madrid, Spain, 28222
Contact: Alberto Forteza    +34 63 62 75 497    apforteza@yahoo.es   
Sweden
Sahlgrenska University Hospital Recruiting
Gothenburg, Västra Götalands Regionen, Sweden, 412 34
Contact: Göran Dellgren    +46 (0) 31-342 88 63    goran.dellgren@vgregion.se   
United Kingdom
Freeman Hospital Not yet recruiting
Newcastle, Newcastle Upon Tyne, United Kingdom, NE77DN
Contact: Stephen Clark    +44 (0) 77 79 27 33 88    Stephen.clark@newcastle.ac.uk   
Queen Elisabeth Hospital Not yet recruiting
Birmingham, United Kingdom, B152TH
Contact: Aaron Ranasinghe    +44 (0) 75 00 78 24 11    Aaron.ranasinghe@uhb.nhs.uk   
Sponsors and Collaborators
XVIVO Perfusion
Investigators
Layout table for investigator information
Principal Investigator: Filip Rega, MD UZ Leuven
Tracking Information
First Submitted Date  ICMJE June 4, 2019
First Posted Date  ICMJE June 19, 2019
Last Update Posted Date March 1, 2021
Actual Study Start Date  ICMJE November 25, 2020
Estimated Primary Completion Date January 31, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 12, 2020) 		30 days mortality and 30 days graft dysfunction [ Time Frame: 30 days ]
The Primary End-Point is defined as time-to-first-event of cardiac related death, moderate or severe primary graft dysfunction of the left ventricle or primary graft dysfunction of the right ventricle (according to Kobashigawa et al., 2014), acute cellular rejection ≥2R (according to Stewart et al., 2005) or graft failure (use of mechanical circulatory support or retransplantation) within 30 days.
Original Primary Outcome Measures  ICMJE
 (submitted: June 18, 2019) 		30 days mortality and 30 days graft dysfunction [ Time Frame: 30 days ]
The Primary End-Point is defined as first-time-to-event of either death, primary graft dysfunction ≥2 (according to Kobashigawa et al 2014), acute cellular rejection ≥2R (according to Stewart et al 2005) or ECMO
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 29, 2020)
  • 1 year mortality and 1 year graft dysfunction [ Time Frame: 1 year ]
    The key secondary endpoint is defined as time-to-first-event of either any cause of death, moderate or severe PGD-LV or PGD-RV (according to Kobashigawa et al., 2014), acute cellular rejection ≥2R (according to Stewart et al., 2005) or graft failure (use of mechanical circulatory support or retransplantation) or CAV ≥ 1 (according to Mehra, 2010) within 12 months.
  • 30 days and 1 year mortality and graft dysfunction [ Time Frame: 30 days and 1 year ]
    The individual variables included in the composite primary endpoint at 30 days and 1 year analyzed as time-to-first-event.
  • CKMB [ Time Frame: 3 days ]
    Creatine kinase MB (CKMB) at 6 ±2 h, 24 ±6 h, 48±6 h and 72±6 h after cross clamp removal
  • TnI [ Time Frame: 3 days ]
    Tropinin I (TnI) at 6 ±2 h, 24 ±6 h, 48±6 h and 72±6 h after cross clamp removal
  • ProBNP [ Time Frame: 3 days ]
    Pro Brain Natriuretic Protein (ProBNP) at 6 ±2 h, 24 ±6 h, 48±6 h and 72±6 h after cross clamp removal
  • Stay in ICU [ Time Frame: 1 year ]
    Length of Stay at Intensive Care Unit, reported as number of days
  • Cardiac Transplant Events [ Time Frame: 1 year ]
    Incidence of Major Adverse Cardiac Transplant Events
  • Postoperative use of mechanical circulatory support [ Time Frame: 1 year ]
    Incidence of use of postoperative mechanical circulatory support, reported as number of days
  • Postoperative duration of mechanical circulatory support [ Time Frame: 1 year ]
    Duration of use of postoperative mechanical circulatory support, reported as number of days
  • Overall success/failure 30 days [ Time Frame: 30 days ]
    Success is defined as a recipient that are transplanted and alive at 30 days without any of the complication in the primary endpoint before 30 days.
  • Overall success/failure 1 year [ Time Frame: 1 year ]
    Success is defined as a recipient that are transplanted and alive at 1 year without any of the complication given in key secondary endpoint before 1 year.
  • ECHO data (Left ventricular ejection fraction) [ Time Frame: 24 hours ]
    ECHO data with Left ventricular ejection fraction in percentage within 24 hours after transplantation
  • ECHO data (Left ventricular ejection fraction) [ Time Frame: 1 week ]
    ECHO data with Left ventricular ejection fraction in percentage 1 week after transplantation
  • ECHO data (Left ventricular ejection fraction) [ Time Frame: 6 months ]
    ECHO data with Left ventricular ejection fraction in percentage 6 months after transplantation
  • ECHO data (Left ventricular ejection fraction) [ Time Frame: 1 year ]
    ECHO data with Left ventricular ejection fraction in percentage 1 year after transplantation
  • ECHO data (Right ventricular ejection fraction) [ Time Frame: 24 hours ]
    ECHO data with Right ventricular ejection fraction in percentage within 24 hours after transplantation
  • ECHO data (Right ventricular ejection fraction) [ Time Frame: 1 week ]
    ECHO data with Right ventricular ejection fraction in percentage 1 week after transplantation
  • ECHO data (Right ventricular ejection fraction) [ Time Frame: 6 months ]
    ECHO data with Right ventricular ejection fraction in percentage 6 months after transplantation
  • ECHO data (Right ventricular ejection fraction) [ Time Frame: 1 year ]
    ECHO data with Right ventricular ejection fraction in percentage 1 year after transplantation
  • ECHO data (Tricuspid annular plane systolic excursion) [ Time Frame: 24 hours ]
    ECHO data with Tricuspid annular plane systolic excursion (TAPSE) in mm within 24 hours after transplantation
  • ECHO data (Tricuspid annular plane systolic excursion) [ Time Frame: 1 week ]
    ECHO data with Tricuspid annular plane systolic excursion (TAPSE) in mm 1 week after transplantation
  • ECHO data (Tricuspid annular plane systolic excursion) [ Time Frame: 6 months ]
    ECHO data with Tricuspid annular plane systolic excursion (TAPSE) in mm 6 months after transplantation
  • ECHO data (Tricuspid annular plane systolic excursion) [ Time Frame: 1 year ]
    ECHO data with Tricuspid annular plane systolic excursion (TAPSE) in mm 1 year after transplantation
Original Secondary Outcome Measures  ICMJE
 (submitted: June 18, 2019) 		1 year mortality and 1 year graft dysfunction [ Time Frame: 1 year ]
The main secondary endpoint is defined as first-time-to-event of either death, Acute Cellular Rejection (ACR) ≥2R (according to Stewart et al 2005), biopsy proven Antibody Mediated Rejection (AMR), re-transplant, implanted heart assist or Cardiac Allograft Vasculopathy (CAV) (according to Mandeep et al 2010) (angiography at 1 year or earlier when presenting symptoms), within 90-days and one year after heart transplantation
Current Other Pre-specified Outcome Measures
 (submitted: June 29, 2020)
  • Serious adverse device effects [ Time Frame: 1 year ]
    Incidence of any serious adverse device effects.
  • Adverse device effects [ Time Frame: 1 year ]
    Incidence of any adverse device effects
  • Device dysfunction resulting in loss of transplantable heart [ Time Frame: 12 hours ]
    Number of transplantable hearts lost due to device dysfunction
  • Intra operative details; duration of ECC [ Time Frame: 12 hours ]
    Duration of ECC in minutes
  • Intra operative details; duration of cross clamp [ Time Frame: 12 hours ]
    Duration of cross clamp in minutes
  • Intra operative details; duration of surgery [ Time Frame: 12 hours ]
    Duration of surgery in minutes
  • Intra operative details; attempts to wean off ECC [ Time Frame: 12 hours ]
    Number of attempts to wean off ECC
  • Intra operative details; need for inotropic support [ Time Frame: 12 hours ]
    Need for inotropic support (inotropic score)
  • Intra operative details; need for pulmonary vasodilator [ Time Frame: 12 hours ]
    Need for pulmonary vasodilator
  • Intra operative details; defibrillations [ Time Frame: 12 hours ]
    Number of defibrillations
  • Intra operative details; arryhythmias [ Time Frame: 12 hours ]
    Occurence of arryhythmias
  • Intra operative details; conduction abnormalities [ Time Frame: 12 hours ]
    Number of conduction abnormalities
  • Intra operative details; Left ventricular ejection fraction (LVEF) [ Time Frame: 12 hours ]
    LVEF in percentage
  • Intra operative details; Right ventricular ejection fraction (RVEF) [ Time Frame: 12 hours ]
    RVEF in percentage
  • Intra operative details; Mitral valve regurgitations [ Time Frame: 12 hours ]
    Grade of mitral valve regurgitations
  • Intra operative details; Tricuspid valve regurgitations [ Time Frame: 12 hours ]
    Occurence of tricuspid vavle regurgitations
  • Arterial blood gas lactate [ Time Frame: 6 hours ]
    Arterial blood gas lactate at 6 hours
  • Arterial blood gas lactate [ Time Frame: 24 hours ]
    Arterial blood gas lactate at 24 hours
  • Pro-BNP during follow up [ Time Frame: 1 year ]
    Pro-BNP at predefined time points during follow-up.
Original Other Pre-specified Outcome Measures
 (submitted: June 18, 2019)
  • CKMB [ Time Frame: 3 days ]
    CKMB Creatine kinase MB (CKMB) in μg/L at 6, 12, 24, 48 and 72 h after cross clamp removal.
  • TnI [ Time Frame: 3 days ]
    Tropinin I (TnI) in μg/L at 6, 12, 24, 48 and 72 h after cross clamp removal.
  • ProBNP [ Time Frame: 3 days ]
    Pro Brain Natriuretic Protein (ProBNP) in ng/I at 6, 12, 24, 48 and 72 h after cross clamp removal.
  • Renal Support [ Time Frame: 30 days ]
    Need and duration of mechanical renal support during first 30 days post transplantation will be followed up by checking the fluid balance.
  • Inotropic Support [ Time Frame: 3 days ]
    Need for inotropic support and/or IABP to given in dose per kg and with an inotropic score in first 6, 12, 24, 48 and 72 hours after removal of cross clamp.
  • ECMO [ Time Frame: 7 days ]
    ECMO use within 7 days and time of use will be followed by a yes or no in the CRF forms.
 
Descriptive Information
Brief Title  ICMJE Non-ischemic Preservation of the Donor Heart in Heart Transplantation
Official Title  ICMJE Non-ischemic Preservation of the Donor Heart in Heart Transplantation - a Randomized, Controlled, Multicenter Trial
Brief Summary The study intends to compare standard ischemic cold static storage (ICSS) of retrieved hearts intended to be transplanted, to non-ischemic heart preservation (NIHP) in a randomized clinical multicentre trial. The primary hypothesis is that the non-ischemic hypothermic cardioplegic preservation (NIHP) is safe and superior to ischemic cold static storage (ICSS) of donor hearts. The study will investigate the safety and superiority of the new methodology in terms of improved immediate and prolonged organ function in adult heart transplanted patients.
Detailed Description This study will investigate if non-ischemic heart preservation (NIHP) with the XVIVO heart preservation devices could improve clinical outcome of patients receiving hearts after use of the technology compared to after use of standard cold ischemic preservation. This will be investigated in a European multicentre randomized controlled clinical trial. For technical reasons, blinding to the involved clinical personnel is not possible, however, biopsies will be blinded to study pathologists. The trial will include 202 recipients that have been randomized through their heart donor. The primary outcome of the study is a clinically relevant composite including graft survival, primary graft dysfunction, rejection and use of circulatory mechanical support, within 30 days and also including Cardiac Allograft Vasculopathy within 12 months. As secondary outcomes, molecular markers related to cardiac injury CKMB, ProBNP and TNI will be investigated as well as markers of the inflammatory response. Safety aspects such as effect on other organs and machine defects will also be monitored. The study population is adults, listed for heart transplantation and donors accepted as heart donors according to standard hospital procedures. Specific recipient exclusion criteria related to pre-transplant ECMO support, patients undergoing pre-transplant desensitization protocol, patients with Grown-Up Congenital Heart Disease, patients with severe kidney or liver dysfunction, patients with septicaemia, and patients diagnosed with Systemic Lupus Erythematous, sarcoidosis or amyloidosis are excluded. Cardiac death donors and donors with previous sternotomy are excluded. The study hypothesis is that NIHP better preserves the endothelium and myocyte function of the heart resulting in improved short- and medium-term recipient outcome, without inducing any new significant risks to the retrieved heart or the recipient. This is believed to be accomplished through continuous oxygenation of the heart via perfusion of the coronary arteries using an optimized preservation solution, mimicking the normal environment for the endothelium.
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Other
Condition  ICMJE Heart Transplantation
Intervention  ICMJE
  • Device: XVIVO heart preservation devices
    The intervention is to preserve hearts during transportation cold, cardioplegic and non-ischemic, with a high oncotic and hormone supplemented perfusate.
  • Device: Standard ICSS
    Cold static preservation using standard preservation solution
Study Arms  ICMJE
  • Experimental: Non-ischemic heart preservation (NIHP)
    Continous cold cardioplegic perfusion of hearts
    Intervention: Device: XVIVO heart preservation devices
  • Active Comparator: Ischemic cold static storage (ICSS)
    Standard preservation technique
    Intervention: Device: Standard ICSS
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 26, 2019) 		202
Original Estimated Enrollment  ICMJE
 (submitted: June 18, 2019) 		138
Estimated Study Completion Date  ICMJE December 31, 2023
Estimated Primary Completion Date January 31, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria recipient:

  • Age ≥18 years
  • Signed informed consent form
  • Listed for heart transplantation

Inclusion criteria donor:

  • Age ≥18 and ≤70 years
  • Accepted as heart donor by the transplant team
  • (research consent from the donor if required in country)

Exclusion Criteria recipient:

  • Previous solid organ transplantation
  • Grown-up congenital heart disease (GUCH)
  • Kidney failure eGFR<40 at listing, calculated by CDK-EPI Creatinine, or ultrafiltration or dialysis or rapidly deteriorating kidney function due to a diagnosed renal disease
  • Coagulopathy due to known hepatic disease or heparin induced thrombocytopenia
  • Patient diagnosed with Systemic Lupus Erythematous, sarcoidosis or amyloidosis
  • Ongoing septicemia defined as positive blood culture (including with a durable VAD)
  • Incompatible blood group
  • Not able to understand the information provided during the informed consent procedure
  • Combined organ transplantation candidates
  • Patient already consented for another transplant related intervention study
  • Patients under pre-transplant desensitization protocol
  • Short term mechanical circulatory support pre-transplantation (Except for Intra-Aortic Balloon Pump)

Exclusion criteria donor:

  • Previous sternotomy
  • DCD hearts
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Marina Fredholm, M.Sc. +46 (0)73 421 42 69 marina.fredholm@xvivoperfusion.com
Contact: Andreas Wallinder, MD, PhD +46 (0)73-5192142 andreas.wallinder@xvivoperfusion.com
Listed Location Countries  ICMJE Belgium,   France,   Germany,   Italy,   Spain,   Sweden,   United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03991923
Other Study ID Numbers  ICMJE NIHP2019
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party XVIVO Perfusion
Study Sponsor  ICMJE XVIVO Perfusion
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Filip Rega, MD UZ Leuven
PRS Account XVIVO Perfusion
Verification Date February 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

治疗医院

新药特效药