Non-ischaemic Heart Preservation Versus Standard Cold Storage in Human Heart Transplantation (NIHP2)
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|ClinicalTrials.gov Identifier: NCT04066127|
Recruitment Status : Not yet recruiting
First Posted : August 26, 2019
Last Update Posted : August 26, 2019
The overall aim of this study is to compare a new state-of-the-art ex-vivo organ preservation method with standard ischemic cold static storage of donor hearts in adult cardiac transplantation.
Standard heart preservation before transplantation consists of cold ischemic storage of the heart. Clinical studies have shown that the morbidity and mortality risk increases with the extension of the allograft ischemic time over four hours. For each additional hour the mortality risk increase with 25% the first year. This time constraint is costly and results in severe logistical problems, leading to loss of transplantable organs. The preliminary results from our safety study, where six patients transplanted with the new state-of-the-art ex-vivo organ preservation method, have shown promising results.
The study is a multicenter, prospective, open, blinded endpoint, randomized, controlled clinical trial. The primary end-point is survival free of acute cellular rejection (ACR) and retransplantation within 1-year post-transplant. ACR will be assessed blinded. The secondary end-points are ischemia/reperfusion injury, early graft dysfunction, and QoL.
|Condition or disease||Intervention/treatment||Phase|
|Transplant; Failure, Heart||Device: Non-ischemic heart preservation (NIHP) Device: Standard ischemic cold static storage (SCS)||Not Applicable|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||50 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Single (Outcomes Assessor)|
|Masking Description:||Acute cellular rejection assessment will be performed by a blinded access|
|Official Title:||A Randomized Controlled Trial Comparing a New State-of-the-art Non Ischemic Heart Preservation Method With the Standard Ischemic Cold Static Storage Method of Donor Hearts in Adult Heart Transplantation|
|Estimated Study Start Date :||October 1, 2019|
|Estimated Primary Completion Date :||December 31, 2021|
|Estimated Study Completion Date :||December 31, 2022|
Experimental: Non-ischemic heart preservation (NIHP)
Non-ischemic hypothermic perfusion (NIHP): The donor heart is preserved using a portable heart-lung machine. The device perfuse the heart continuously with a a new preservation solution at a temperature of 8°C.
Device: Non-ischemic heart preservation (NIHP)
The device is a miniaturized and fully automated heart-lung machine, housed in a portable device (weight 32 kg), that enables transportation between hospitals. The reservoir is filled with 2.5 liters of the perfusion solution plus approximately 500 mL compatible washed and leucocyte-filtered red blood cells from the hospital blood bank. The NIHP system software is adjusted to maintain a mean blood pressure of 20-25 mmHg in the aortic root, giving a coronary flow between 150 mL/min and 250 mL/min.
Standard cold storage (SCS)
Standard cold static storage (SCS): The donor heart is preserved using a standard crystalloid cardioplegia. The heart is in then storage i a transport box containing ice to keep the temperature around 4-8°C. The device does not perfuse the heart.
Device: Standard ischemic cold static storage (SCS)
The device is a cool box that enables transportation between hospitals. The heart is stored on ice slush in the box at a temperature of approximately 4-8 °C.
- Survival free of acute cellular rejection and re-transplantation [ Time Frame: One year ]The primary end-point is defined as the difference between the two treatment arms in survival free of acute cellular rejection ≥1R and re-transplantation within one year. Acute cellular rejection assessment is based on post-transplant myocardial biopsy information and standard clinical evaluation.
- I/R-tissue injury [ Time Frame: 72 hours ]Cardiac troponin I and T, and kinase-muscle/brain measured at end of preservation and 6, 12, 24, 32, 48, and 72 hours after cross-clamp release.
- Early allograft dysfunction [ Time Frame: 24 hours ]Moderate or severe primary graft dysfunction (PGD) within 24 hours after x-clamp release. PGD is measured and defined according to Kobashigawa.
- Measuring health status [ Time Frame: One year ]The EQ-5D-5L instrument will be used. This instrument assesses morbidity, self-care, usual activity, pain, and anxiety and depression of patients. The EQ-5D-5L will be completed pre-transplant and at 1, 3, 6, and 12 months visits.
- Organ discard rate [ Time Frame: 24 hours ]Number of donor heart which was discarded after retrieval to the transplant unit
- Heart function [ Time Frame: One year ]An echo is performed day 1, 7, and 3 months and one year post transplant daily to monitor the heart function. Ejection fraction, ventricular dimensions, valve competence TAPSE.
- Cardiovascular magnetic resonance [ Time Frame: 30 days ]Patient will be examined by CMR at 21 ±7 days post transplantation with a 1.5 Tesla MR scanner with measurements of cardiac dimensions, cardiac output, local and global myocardial perfusion, tissue characterization, and extracellular volume measurements.
- Acute cellular rejection [ Time Frame: One year ]A national protocol for surveillance and monitoring the patients, including collecting 14 endomyocardial biopsies during the first year. The endomyocardial biopsies will be used to measure grade of acute cellular rejection. Assessment of the biopsies will be performed blinded by three independent pathologists
- Functional capacity [ Time Frame: One year ]Recording the patient's activity. Patient will carry an activity monitor (step gauge, accelerator, calorie meter) for the whole day, except when sleeping. The activity clock will also collect information about the patient's heart rhythm. Patient retains the activity meter throughout the study period.
- Resource use [ Time Frame: One year ]Length of Stay at Intensive Care Unit (ICU) calculated from time patient arrives into the ICU until the patient is discharged from the ICU. Length of Stay at hospital calculated from date and time of surgery until date and time that the patient is discharged from the hospital. Number of visits to professional healthcare within first year post-transplant.
- Costs for organ procurement [ Time Frame: 24 hours ]Defined as cost for personality, transportation and equipment
- Severe adverse events - Cardiac failure [ Time Frame: 30 days ]Cardiac failure is determined as the need for intra-aortic balloon pump (IABP) and/or mechanical circulatory extra corporal support (ECMO) within seven days or need for re-transplantation due to graft failure
- Severe adverse events - Acute bleeding [ Time Frame: 30 days ]Acute bleeding is defined according to the BARC type IV criteria (>2000 ml/24 h and/or requiring re-operation for bleeding, and/or intracranial bleeding, and/or transfusion of >5 red blood cell concentrates/48 h)
- Severe adverse events - Respiratory failure [ Time Frame: 30 days ]Respiratory failure is defined as impairment of respiratory function requiring re-intubation, tracheostomy, vvECMO or the inability to discontinue invasive ventilator support within 48 h after CPB due to respiratory issues and not due to sedation issues.
- Severe adverse events - Acute kidney failure [ Time Frame: 30 days ]Acute kidney failure is defined according to the KDIGO criteria as an increase in serum creatinine of >27 μmol/L within 48 hours or 1.5 times baseline within seven days.
- Severe adverse events - Permanent stroke [ Time Frame: 30 days ]Permanent stroke is defined as an episode of a computer tomography (CT) verified acute neurological dysfunction to be caused by ischemia or haemorrhage, persisting ≥24 hours or until death.
- Severe adverse events - Permanent pacemaker [ Time Frame: 30 days ]Permanent pacemaker is defined as need for a permanent pacemaker implantation two weeks after transplantation
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04066127
|Contact: Johan Nilsson, MD, PhD||+46 firstname.lastname@example.org|
|Skane University Hospital|
|Lund, Skane, Sweden, 22185|
|Contact: Johan Nilsson, MD, PhD 171000 ext 46 email@example.com|