A Randomized Controlled Trial Comparing Non-ischemic to Ischemic Preservation in Adult Cardiac Transplantation

NCT03150147 | Completed DMC

• 1 other identifier: 2016/603
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 1

Brief Summary

The overall aim of this proposal 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 has shown that the morbidity and mortality risk increases with extension of the allograft ischemic time over four hours. For each additional hour the mortality risk increase with 25% the first year. This time constrained is costly and results in severe logistical problems, leading to loss of transplantable organs. Initially the study is prospective, single-institution, open-label, non-randomised trial comparing the NIHP method with the conventionally SCS in adult heart transplanted patients at Skane University Hospital, Lund, Sweden. Six patients will be transplanted using the non-ischemic hypothermic cardioplegic perfusion. These will be compared with contemporary control patients transplanted with standard ischemic cold static storage. The results will be analysed and reported. After the initially six patients have been completed, the study will become a single center, prospective, open, blinded endpoint, randomized, controlled clinical trial including 34 patients. The primary end-point is a composite of mortality, primary graft dysfunction (PGD), need for extra corporal support, or acute cellular rejection (ACR) within 30- days post-transplant. PGD and ACR will be accessed blinded.An improved preservation of the transplanted organ will reduce the major limitations for survival in the early post-transplant period such as non-specific graft failure and acute rejection. Furthermore, it will make it possible to increase the donor pool.

Conditions

Transplant; Failure, Heart

Keywords

Organ preservation; Survival; Graft function; Reperfusion injury; Heart transplantation

Outcome Measures

Primary Outcomes (1)

• Short-term graft failure

  The Primary End-Point is defined as a composite endpoint of patient death due to graft failure, re-transplantation due to graft failure, severe primary graft dysfunction (PGD), need for extra corporal mechanical support such as ECMO within 7 days post transplantation, or acute cellular rejection (ACR) ≥ grade 2. PGD grading is done according to the International Society of Heart and Lung Transplantation guidelines. ACR assessment is based on post-transplant myocardial biopsy information and standard clinical evaluation.

  Within 30-days post-transplantation

Secondary Outcomes (3)

• Long-term graft failure

  Within 12-months post-transplantation

• Ischemia and reperfusion injury

  Within 30-days post-transplantation

• Ischemia and reperfusion injury

  Within 30-days post-transplantation

Other Outcomes (10)

• Postoperative renal function

  Within 30-days post-transplantation

• Postoperative liver function

  Within 30-days post-transplantation

• Length of Stay

  Within 12-months post-transplantation

Study Arms (2)

Non-ischemic preservation.

EXPERIMENTAL

Non-ischemic hypothermic perfusion (NIHP): The device, a portable heart-lung machine, is continous/intermittent perfused the heart with a new preservation solution at a temperature of 8°C.

Other: Non-ischemic preservation

Standard ischemic storage.

OTHER

Ischemic cold static storage: a crystalloid solution (cardioplegia) is used to stop and preserve the heart. The heart is storage i a transport box containing ice to keep the temperature around 8°C.

Other: Ischemic cold static storage

Interventions

Non-ischemic preservation OTHER

The device is a portable heart-lung machine; an automatic pressure and flow-controlled perfusion system. The heart is submerged in a solution and the medium is circulated in the heart, at a temperature of 8°C.

Non-ischemic preservation.

Ischemic cold static storage OTHER

Standard ischemic cold static storage; a crystalloid solution (cardioplegia) is used to stop and preserve the heart. Cardioplegia is given. The heart is storage i a transport box containing ice to keep the temperature around 8°C.

Standard ischemic storage.

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Previous solid organ or bone marrow transplantation
• or more previous sternotomies
• known malignancy
• kidney failure (estimated creatinine clearness, GFR \<30)
• liver failure (ASAT, ALAT or total Bilirubin) \> 5 times upper limit of normal, or INR \>2.0,
• ongoing septicemia
• systemic inflammatory disorders treated with corticosteroids
• not able to understand Swedish

Sponsors & Collaborators

• Region Skane: lead

Study Sites (1)

Skane University Hospital

Lund, Skåne County, 22185, Sweden

Location

Related Publications (9)

• Nilsson J, Ohlsson M, Hoglund P, Ekmehag B, Koul B, Andersson B. The International Heart Transplant Survival Algorithm (IHTSA): a new model to improve organ sharing and survival. PLoS One. 2015 Mar 11;10(3):e0118644. doi: 10.1371/journal.pone.0118644. eCollection 2015.

  PMID: 25760647 BACKGROUND

• Messer S, Ardehali A, Tsui S. Normothermic donor heart perfusion: current clinical experience and the future. Transpl Int. 2015 Jun;28(6):634-42. doi: 10.1111/tri.12361. Epub 2014 Jul 7.

  PMID: 24853906 BACKGROUND

• 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

• 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 , Volume 35 , Issue 4 , S193

  BACKGROUND

• Zhou L, Zang G, Zhang G, Wang H, Zhang X, Johnston N, Min W, Luke P, Jevnikar A, Haig A, Zheng X. MicroRNA and mRNA signatures in ischemia reperfusion injury in heart transplantation. PLoS One. 2013 Nov 20;8(11):e79805. doi: 10.1371/journal.pone.0079805. eCollection 2013.

  PMID: 24278182 BACKGROUND

• Ardehali A, Esmailian F, Deng M, Soltesz E, Hsich E, Naka Y, Mancini D, Camacho M, Zucker M, Leprince P, Padera R, Kobashigawa J; PROCEED II trial investigators. Ex-vivo perfusion of donor hearts for human heart transplantation (PROCEED II): a prospective, open-label, multicentre, randomised non-inferiority trial. Lancet. 2015 Jun 27;385(9987):2577-84. doi: 10.1016/S0140-6736(15)60261-6. Epub 2015 Apr 14.

  PMID: 25888086 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

• Eltzschig HK, Eckle T. Ischemia and reperfusion--from mechanism to translation. Nat Med. 2011 Nov 7;17(11):1391-401. doi: 10.1038/nm.2507.

  PMID: 22064429 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 RESULT

MeSH Terms

Conditions

Reperfusion Injury

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Johan Nilsson, MD, PhD

  Lund University and Skåne University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: PGD and ACR assessment will be performed by a blinded access
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Initially the study is a single center, prospective, open, blinded endpoint, non-randomized, controlled clinical trial. Six patients will be transplanted with the NICHCP method. These will be compared with contemporary control patients transplanted with standard ICSS (N=25). An analyze will be performed when these six patients has passed 180-days post-transplant. The result will be reported. After the the initially study has been completed, the study will become a single center, prospective, open, blinded endpoint, randomized, controlled clinical trial. The continued study will comprise 17 patients in the test group and 17 control patients. The main outcomes will be reported on intention to treat basis. PGD and ACR assessment will be performed by a blinded access. Randomisation will be computer generated.

Study Record Dates

• First Submitted: May 8, 2017
• First Posted: May 12, 2017
• Study Start: March 1, 2017
• Primary Completion: June 30, 2020
• Study Completion: June 30, 2020
• Last Updated: April 28, 2021

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1)