Non-ischaemic Heart Preservation Versus Standard Cold Storage in Human Heart Transplantation

NCT04066127 | Enrolling By Invitation DMC

• 1 other identifier: 2018/941
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Transplant; Failure, Heart

Keywords

Heart preservation; Ex-vivo perfusion; Heart transplantation; Acute cellular rejection; Survival

Outcome Measures

Primary Outcomes (1)

• Survival free of acute cellular rejection and re-transplantation

  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.

  One year

Secondary Outcomes (11)

• Quality-of-life pre- and posttransplantation

  One year

• I/R-tissue injury

  72 hours

• Immediate graft dysfunction

  24 hours

• Intermediate graft function

  21 ±7 days post transplantation

• Chronicle graft rejection

  One year post transplant (11- 15 months)

Other Outcomes (5)

• Organ discard rate

  24 hours

• Resource use

  One year

• Costs for organ procurement

  24 hours

Study Arms (2)

Non-ischemic heart preservation (NIHP)

EXPERIMENTAL

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)

Standard cold storage (SCS)

OTHER

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)

Interventions

Non-ischemic heart preservation (NIHP) DEVICE

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.

Non-ischemic heart preservation (NIHP)

Standard ischemic cold static storage (SCS) DEVICE

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.

Standard cold storage (SCS)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Previous solid organ transplantation
• Grown-up congenital heart disease (GUCH)
• Kidney failure eGFR\<40, 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
• 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
• Patients under pre-transplant desensitization protocol
• Short term mechanical support pre-transplant (ECMO)
• Patient diagnosed with Systemic Lupus Erythematous, sarcoidosis or amyloidosis
• Combined organ transplantation candidates
• Patient already consented for another transplant related intervention study
• Age ≤70 years
• Accepted as heart donor by the transplant team (research consent from the donor if required in country)
• Previous sternotomy

Sponsors & Collaborators

• Region Skane: lead
• Lund University: collaborator
• Skane University Hospital: collaborator

Study Sites (1)

Skane University Hospital

Lund, Skåne County, 22185, Sweden

Location

Related Publications (10)

• Steen S, Paskevicius A, Liao Q, Sjoberg T. Safe orthotopic transplantation of hearts harvested 24 hours after brain death and preserved for 24 hours. Scand Cardiovasc J. 2016 Jun;50(3):193-200. doi: 10.3109/14017431.2016.1154598. Epub 2016 Apr 4.

  PMID: 26882241 BACKGROUND

• Nilsson J, Jernryd V, Qin G, Nozohoor S, Goncalves DC, Ragnarsson S, Paskevicius A, Johansson M, Warheim J, Hoglund P, Sjoberg T, Steen S. Non Ischemic Heart Preservation. J Heart Lung Transpl 2018;37:S13-S.

  BACKGROUND

• Jernryd V, Metzsch C, Andersson B, Nilsson J. Organ Preservation and Reperfusion Influence on Outcome after Heart Transplantation. The Journal of Heart and Lung Transplantation 2016;35:S193-S.

  BACKGROUND

• Nilsson J, Ohlsson M, Stehlik J, Lund L, Andersson B. Prediction of Primary Graft Dysfunction After Heart Transplantation. J Heart Lung Transpl 2015;34:S35-S.

  BACKGROUND

• Qin G, Sjoberg T, Liao Q, Sun X, Steen S. Intact endothelial and contractile function of coronary artery after 8 hours of heart preservation. Scand Cardiovasc J. 2016 Oct-Dec;50(5-6):362-366. doi: 10.1080/14017431.2016.1213876. Epub 2016 Aug 3.

  PMID: 27420646 BACKGROUND

• Steen S. Preservation of the endothelium in cardiovascular surgery-some practical suggestions--a review. Scand Cardiovasc J. 2001 Oct;35(5):297-301. doi: 10.1080/140174301317116253. No abstract available.

  PMID: 11771819 BACKGROUND

• Nilsson J, Jernryd V, Qin G, Paskevicius A, Sjoberg T, Hoglund P, Steen S. Non Ischemic Heart Preservation - Results from the Safety Study. J Heart Lung Transpl 2019;38:S26-S.

  BACKGROUND

• Steen S, Sjoberg T, Pierre L, Liao Q, Eriksson L, Algotsson L. Transplantation of lungs from a non-heart-beating donor. Lancet. 2001 Mar 17;357(9259):825-9. doi: 10.1016/S0140-6736(00)04195-7.

  PMID: 11265950 BACKGROUND

• Nilsson J, Jernryd V, Qin G, Paskevicius A, Metzsch C, Sjoberg T, Steen S. A nonrandomized open-label phase 2 trial of nonischemic heart preservation for human heart transplantation. Nat Commun. 2020 Jun 12;11(1):2976. doi: 10.1038/s41467-020-16782-9.

  PMID: 32532991 BACKGROUND

• Pigot H, Steen S, Nilsson J. Comparing non-ischaemic heart preservation (NIHP) with ischaemic static cold storage of donor hearts in adult cardiac transplantation: study protocol for a randomised controlled trial. BMJ Open. 2025 Jun 25;15(6):e100553. doi: 10.1136/bmjopen-2025-100553.

  PMID: 40562558 DERIVED

Study Officials

• Johan Nilsson, MD, PhD

  Region Skane

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Acute cellular rejection assessment will be performed by a blinded access
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: August 21, 2019
• First Posted: August 26, 2019
• Study Start: July 1, 2020
• Primary Completion: December 31, 2025
• Study Completion (Estimated): December 31, 2026
• Last Updated: May 8, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1)