Non-ischemic Preservation of the Donor Heart in Heart Transplantation

Heart Transplantation Clinical Trial

Official title:

Non-ischemic Preservation of the Donor Heart in Heart Transplantation - a Randomized, Controlled, Multicenter Trial

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03991923
• Other study ID #: NIHP2019
• Status: Active, not recruiting
• Phase: N/A
• Start date: November 25, 2020
• Est. completion date: August 31, 2024

Study information

• Verified date: November 2023
• Source: XVIVO Perfusion
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 230
• Est. completion date: August 31, 2024
• Est. primary completion date: August 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

• Subject diagnosed with Systemic Lupus Erythematous, sarcoidosis or amyloidosis

• Known ongoing septicemia defined as positive blood culture immediately prior to the transplant (including with a durable VAD)

• Incompatible blood group

• Not able to understand the information provided during the informed consent procedure

• Combined organ transplantation candidates

• Subject already enrolled in another transplant related intervention study

• Subjects under pre-transplant desensitization protocol (including plasma exchange in conjunction with the transplant surgery)

• Mechanical circulatory support pre-transplantation (except durable Left ventricular assist device or Intra-aortic balloon pump)

Exclusion criteria donor:

• Previous sternotomy

• DCD hearts

Related Conditions & MeSH terms

• Heart Transplantation

Intervention

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.
• Standard ICSS
Cold static preservation using standard preservation solution

Locations

Country	Name	City	State
Austria	Allgemeines Krankenhaus der Stadt Wien	Wien
Belgium	UZ Leuven	Leuven	Flemish Brabant
France	Hôpital Bichat Claude-Bernard	Paris
France	Institut de cardiologie, Chirurgie thoracique et cardiovasculaire La Pitié Salpetrière	Paris	Paris Cedex
Germany	Universitätsklinik der Ruhr-Universität Bochum	Bad Oeynhausen
Germany	Deutschen Herzzentrum Berlin	Berlin	Brandenburg
Germany	Universitätsklinikum Düsseldorf	Duesseldorf
Germany	Hannover Medical School	Hanover
Germany	Klinikum der Universität München	München	Bavaria
Italy	Azienda osedalaria di Padova	Padova	Padova PD
Spain	Hospital Puerto de Hierro	Madrid	Majadahonda Madrid
Sweden	Sahlgrenska University Hospital	Gothenburg	Västra Götalands Regionen
United Kingdom	Queen Elisabeth Hospital	Birmingham
United Kingdom	Royal Papworth Hospital	Cambridge
United Kingdom	Freeman Hospital	Newcastle	Newcastle Upon Tyne

Sponsors (1)

Lead Sponsor	Collaborator
XVIVO Perfusion

Countries where clinical trial is conducted

Austria,  Belgium,  France,  Germany,  Italy,  Spain,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Serious adverse device effects	Incidence of any serious adverse device effects.	1 year
Other	Adverse device effects	Incidence of any adverse device effects	1 year
Other	Device dysfunction resulting in loss of transplantable heart	Number of transplantable hearts lost due to device dysfunction	12 hours
Other	Intra operative details; duration of ECC	Duration of ECC in minutes	12 hours
Other	Intra operative details; duration of cross clamp	Duration of cross clamp in minutes	12 hours
Other	Intra operative details; duration of surgery	Duration of surgery in minutes	12 hours
Other	Intra operative details; attempts to wean off ECC	Number of attempts to wean off ECC	12 hours
Other	Intra operative details; need for inotropic support	Need for inotropic support (inotropic score)	12 hours
Other	Intra operative details; need for pulmonary vasodilator	Need for pulmonary vasodilator	12 hours
Other	Intra operative details; defibrillations	Number of defibrillations	12 hours
Other	Intra operative details; arryhythmias	Occurence of arryhythmias	12 hours
Other	Intra operative details; conduction abnormalities	Number of conduction abnormalities	12 hours
Other	Intra operative details; Left ventricular ejection fraction (LVEF)	LVEF in percentage	12 hours
Other	Intra operative details; Right ventricular ejection fraction (RVEF)	RVEF in percentage	12 hours
Other	Intra operative details; Mitral valve regurgitations	Grade of mitral valve regurgitations	12 hours
Other	Intra operative details; Tricuspid valve regurgitations	Occurence of tricuspid vavle regurgitations	12 hours
Other	Arterial blood gas lactate	Arterial blood gas lactate at 6 hours	6 hours
Other	Arterial blood gas lactate	Arterial blood gas lactate at 24 hours	24 hours
Other	Pro-BNP during follow up	Pro-BNP at predefined time points during follow-up.	1 year
Primary	30 days mortality and 30 days graft dysfunction	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.	30 days
Secondary	1 year mortality and 1 year graft dysfunction	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.	1 year
Secondary	30 days and 1 year mortality and graft dysfunction	The individual variables included in the composite primary endpoint at 30 days and 1 year analyzed as time-to-first-event.	30 days and 1 year
Secondary	CKMB	Creatine kinase MB (CKMB) at 6 ±2 h, 24 ±6 h, 48±6 h and 72±6 h after cross clamp removal	3 days
Secondary	TnI	Tropinin I (TnI) at 6 ±2 h, 24 ±6 h, 48±6 h and 72±6 h after cross clamp removal	3 days
Secondary	ProBNP	Pro Brain Natriuretic Protein (ProBNP) at 6 ±2 h, 24 ±6 h, 48±6 h and 72±6 h after cross clamp removal	3 days
Secondary	Stay in ICU	Length of Stay at Intensive Care Unit, reported as number of days	1 year
Secondary	Cardiac Transplant Events	Incidence of Major Adverse Cardiac Transplant Events	1 year
Secondary	Postoperative use of mechanical circulatory support	Incidence of use of postoperative mechanical circulatory support, reported as number of days	1 year
Secondary	Postoperative duration of mechanical circulatory support	Duration of use of postoperative mechanical circulatory support, reported as number of days	1 year
Secondary	Overall success/failure 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.	30 days
Secondary	Overall success/failure 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.	1 year
Secondary	ECHO data (Left ventricular ejection fraction)	ECHO data with Left ventricular ejection fraction in percentage within 24 hours after transplantation	24 hours
Secondary	ECHO data (Left ventricular ejection fraction)	ECHO data with Left ventricular ejection fraction in percentage 1 week after transplantation	1 week
Secondary	ECHO data (Left ventricular ejection fraction)	ECHO data with Left ventricular ejection fraction in percentage 6 months after transplantation	6 months
Secondary	ECHO data (Left ventricular ejection fraction)	ECHO data with Left ventricular ejection fraction in percentage 1 year after transplantation	1 year
Secondary	ECHO data (Right ventricular ejection fraction)	ECHO data with Right ventricular ejection fraction in percentage within 24 hours after transplantation	24 hours
Secondary	ECHO data (Right ventricular ejection fraction)	ECHO data with Right ventricular ejection fraction in percentage 1 week after transplantation	1 week
Secondary	ECHO data (Right ventricular ejection fraction)	ECHO data with Right ventricular ejection fraction in percentage 6 months after transplantation	6 months
Secondary	ECHO data (Right ventricular ejection fraction)	ECHO data with Right ventricular ejection fraction in percentage 1 year after transplantation	1 year
Secondary	ECHO data (Tricuspid annular plane systolic excursion)	ECHO data with Tricuspid annular plane systolic excursion (TAPSE) in mm within 24 hours after transplantation	24 hours
Secondary	ECHO data (Tricuspid annular plane systolic excursion)	ECHO data with Tricuspid annular plane systolic excursion (TAPSE) in mm 1 week after transplantation	1 week
Secondary	ECHO data (Tricuspid annular plane systolic excursion)	ECHO data with Tricuspid annular plane systolic excursion (TAPSE) in mm 6 months after transplantation	6 months
Secondary	ECHO data (Tricuspid annular plane systolic excursion)	ECHO data with Tricuspid annular plane systolic excursion (TAPSE) in mm 1 year after transplantation	1 year