Heart TransplantationNCT03991923
Non-ischemic Preservation of the Donor Heart in Heart Transplantation
A study testing XVIVO heart preservation devices and Standard ICSS in people with Heart Transplantation, run by XVIVO Perfusion at 15 sites in 8 countries.
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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Heart Transplantation
- What is being tested?
- XVIVO heart preservation devices and Standard ICSS
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 230 participants
- Where
- 15 sitesin 8 countries
- Study dates
- 25 Nov 2020to 31 Dec 2028
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥18 years
- Signed informed consent form
- Listed for heart transplantation
- Age ≥18 and ≤70 years
- Accepted as heart donor by the transplant team
- (Research consent from the donor if required in country)
Who cannot join
- 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)
Show all 14Show fewer
- 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)
- Previous sternotomy
- DCD hearts
Trial locations and contacts
15 sites in 8 countries.
15 sites in 8 countries
Germany5 sites
Universitätsklinik der Ruhr-Universität Bochum
Bad Oeynhausen
Deutschen Herzzentrum Berlin
Berlin, Brandenburg, 13353
Universitätsklinikum Düsseldorf
Düsseldorf
Hannover Medical School
Hanover
Klinikum der Universität München
München, Bavaria, 81377
United Kingdom3 sites
Queen Elisabeth Hospital
Birmingham, B152TH
Royal Papworth Hospital
Cambridge
Freeman Hospital
Newcastle, Newcastle Upon Tyne, NE77DN
France2 sites
Institut de cardiologie, Chirurgie thoracique et cardiovasculaire La Pitié Salpetrière
Paris, Paris Cedex, 75651
Hôpital Bichat Claude-Bernard
Paris
Sweden1 site
Sahlgrenska University Hospital
Gothenburg, Västra Götalands Regionen, 412 34
About this study
Official title: Non-ischemic Preservation of the Donor Heart in Heart Transplantation - a Randomized, Controlled, Multicenter Trial
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.
Read the 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.
- Conditions
- Heart Transplantation
- Being tested
- XVIVO heart preservation devices, Standard ICSS
- Keywords
- Non Ischemic Heart Preservation (NIHP), Ischemic cold static storage of donor hearts (ICSS)
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
XVIVO heart preservation devicesDevice
The intervention is to preserve hearts during transportation cold, cardioplegic and non-ischemic, with a high oncotic and hormone supplemented perfusate.
Standard ICSSDevice
Cold static preservation using standard preservation solution
| Study group | Role | What they receive |
|---|---|---|
| Non-ischemic heart preservation (NIHP) | Experimental | Continous cold cardioplegic perfusion of hearts Receives: Device: XVIVO heart preservation devices |
| Ischemic cold static storage (ICSS) | Active comparator | Standard preservation technique Receives: Device: Standard ICSS |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 30 days
Secondary outcomes (23)
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.
Measured: 1 year
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.
Measured: 30 days and 1 year
CKMB
Creatine kinase MB (CKMB) at 6 ±2 h, 24 ±6 h, 48±6 h and 72±6 h after cross clamp removal
Measured: 3 days
TnI
Tropinin I (TnI) at 6 ±2 h, 24 ±6 h, 48±6 h and 72±6 h after cross clamp removal
Measured: 3 days
ProBNP
Pro Brain Natriuretic Protein (ProBNP) at 6 ±2 h, 24 ±6 h, 48±6 h and 72±6 h after cross clamp removal
Measured: 3 days
Stay in ICU
Length of Stay at Intensive Care Unit, reported as number of days
Measured: 1 year
Cardiac Transplant Events
Incidence of Major Adverse Cardiac Transplant Events
Measured: 1 year
Postoperative use of mechanical circulatory support
Incidence of use of postoperative mechanical circulatory support, reported as number of days
Measured: 1 year
Postoperative duration of mechanical circulatory support
Duration of use of postoperative mechanical circulatory support, reported as number of days
Measured: 1 year
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.
Measured: 30 days
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.
Measured: 1 year
ECHO data (Left ventricular ejection fraction)
ECHO data with Left ventricular ejection fraction in percentage within 24 hours after transplantation
Measured: 24 hours
ECHO data (Left ventricular ejection fraction)
ECHO data with Left ventricular ejection fraction in percentage 1 week after transplantation
Measured: 1 week
ECHO data (Left ventricular ejection fraction)
ECHO data with Left ventricular ejection fraction in percentage 6 months after transplantation
Measured: 6 months
ECHO data (Left ventricular ejection fraction)
ECHO data with Left ventricular ejection fraction in percentage 1 year after transplantation
Measured: 1 year
ECHO data (Right ventricular ejection fraction)
ECHO data with Right ventricular ejection fraction in percentage within 24 hours after transplantation
Measured: 24 hours
ECHO data (Right ventricular ejection fraction)
ECHO data with Right ventricular ejection fraction in percentage 1 week after transplantation
Measured: 1 week
ECHO data (Right ventricular ejection fraction)
ECHO data with Right ventricular ejection fraction in percentage 6 months after transplantation
Measured: 6 months
ECHO data (Right ventricular ejection fraction)
ECHO data with Right ventricular ejection fraction in percentage 1 year after transplantation
Measured: 1 year
ECHO data (Tricuspid annular plane systolic excursion)
ECHO data with Tricuspid annular plane systolic excursion (TAPSE) in mm within 24 hours after transplantation
Measured: 24 hours
ECHO data (Tricuspid annular plane systolic excursion)
ECHO data with Tricuspid annular plane systolic excursion (TAPSE) in mm 1 week after transplantation
Measured: 1 week
ECHO data (Tricuspid annular plane systolic excursion)
ECHO data with Tricuspid annular plane systolic excursion (TAPSE) in mm 6 months after transplantation
Measured: 6 months
ECHO data (Tricuspid annular plane systolic excursion)
ECHO data with Tricuspid annular plane systolic excursion (TAPSE) in mm 1 year after transplantation
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jun 2019
- Study start25 Nov 2020
- Primary completion31 Aug 2023
- Study completion31 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Heart TransplantationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 230 participants (actual)
Sponsor and investigators
- Lead sponsor
- XVIVO Perfusion
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Filip Rega, MD, PhD, Principal investigator, UZ Leuven
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03991923
- Sponsor's protocol ID
- NIHP2019
- Status last verified
- Apr 2026
- First submitted
- 4 Jun 2019
- Last updated
- 21 Apr 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Rega F, Lebreton G, Para M, Michel S, Schramm R, Begot E, Vandendriessche K, Kamla C, Gerosa G, Berman M, Boeken U, Clark S, Ranasinghe A, Ius F, Forteza A, Pivodic A, Hennig F, Guenther S, Zuckermann A, Knosalla C, Dellgren G, Wallinder A; NIHP2019 investigators. Hypothermic oxygenated perfusion of the donor heart in heart transplantation: the short-term outcome from a randomised, controlled, open-label, multicentre clinical trial. Lancet. 2024 Aug 17;404(10453):670-682. doi: 10.1016/S0140-6736(24)01078-X.
PubMed 39153817Brouckaert J, Dellgren G, Wallinder A, Rega F. Non-ischaemic preservation of the donor heart in heart transplantation: protocol design and rationale for a randomised, controlled, multicentre clinical trial across eight European countries. BMJ Open. 2023 Dec 28;13(12):e073729. doi: 10.1136/bmjopen-2023-073729.
PubMed 38154894
Study at a glance
From the registry record, last updated by the sponsor on 21 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Non-ischemic Preservation of the Donor Heart in Heart Transplantation - a Randomized, Controlled, Multicenter Trial
- ClinicalTrials.gov ID
- NCT03991923
- Acronym / sponsor ID
- NIHP2019
- Conditions
- Heart Transplantation
- Keywords
- Non Ischemic Heart Preservation (NIHP), Ischemic cold static storage of donor hearts (ICSS)
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 230 participants (actual)
- Lead sponsor
- XVIVO PerfusionIndustry (pharma, biotech, devices)
- Study start
- 25 Nov 2020 (actual)
- Primary completion
- 31 Aug 2023 (actual)
- Study completion
- 31 Dec 2028 (estimated)
- First posted
- 19 Jun 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Non-ischemic heart preservation (NIHP) | Experimental | Device: XVIVO heart preservation devicesContinous cold cardioplegic perfusion of hearts |
| Ischemic cold static storage (ICSS) | Active comparator | Device: Standard ICSSStandard preservation technique |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Age ≥18 years
- Signed informed consent form
- Listed for heart transplantation
- Age ≥18 and ≤70 years
- Accepted as heart donor by the transplant team
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| XVIVO heart preservation devicesThe intervention is to preserve hearts during transportation cold, cardioplegic and non-ischemic, with a high oncotic and hormone supplemented perfusate. | Device | Non-ischemic heart preservation (NIHP) |
| Standard ICSSCold static preservation using standard preservation solution | Device | Ischemic cold static storage (ICSS) |
Primary outcome
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.
23 secondary outcomes
1 year mortality and 1 year graft dysfunction
Time frame: 1 year
30 days and 1 year mortality and graft dysfunction
Time frame: 30 days and 1 year
CKMB
Time frame: 3 days
TnI
Time frame: 3 days
ProBNP
Time frame: 3 days
Stay in ICU
Time frame: 1 year
Cardiac Transplant Events
Time frame: 1 year
Postoperative use of mechanical circulatory support
Time frame: 1 year
Postoperative duration of mechanical circulatory support
Time frame: 1 year
Overall success/failure 30 days
Time frame: 30 days
Overall success/failure 1 year
Time frame: 1 year
ECHO data (Left ventricular ejection fraction)
Time frame: 24 hours
ECHO data (Left ventricular ejection fraction)
Time frame: 1 week
ECHO data (Left ventricular ejection fraction)
Time frame: 6 months
ECHO data (Left ventricular ejection fraction)
Time frame: 1 year
ECHO data (Right ventricular ejection fraction)
Time frame: 24 hours
ECHO data (Right ventricular ejection fraction)
Time frame: 1 week
ECHO data (Right ventricular ejection fraction)
Time frame: 6 months
ECHO data (Right ventricular ejection fraction)
Time frame: 1 year
ECHO data (Tricuspid annular plane systolic excursion)
Time frame: 24 hours
ECHO data (Tricuspid annular plane systolic excursion)
Time frame: 1 week
ECHO data (Tricuspid annular plane systolic excursion)
Time frame: 6 months
ECHO data (Tricuspid annular plane systolic excursion)
Time frame: 1 year
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Apr 2026.
- Derived from this study: PubMed 39153817Rega F, Lebreton G, Para M, Michel S, Schramm R, Begot E, Vandendriessche K, Kamla C, Gerosa G, Berman M, Boeken U, Clark S, Ranasinghe A, Ius F, Forteza A, Pivodic A, Hennig F, Guenther S, Zuckermann A, Knosalla C, Dellgren G, Wallinder A; NIHP2019 investigators. Hypothermic oxygenated perfusion of the donor heart in heart transplantation: the short-term outcome from a randomised, controlled, open-label, multicentre clinical trial. Lancet. 2024 Aug 17;404(10453):670-682. doi: 10.1016/S0140-6736(24)01078-X.
- Derived from this study: PubMed 38154894Brouckaert J, Dellgren G, Wallinder A, Rega F. Non-ischaemic preservation of the donor heart in heart transplantation: protocol design and rationale for a randomised, controlled, multicentre clinical trial across eight European countries. BMJ Open. 2023 Dec 28;13(12):e073729. doi: 10.1136/bmjopen-2023-073729.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Filip Rega, MD, PhD principal investigator
UZ Leuven
15 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing XVIVO heart preservation devices and Standard ICSS in people with Heart Transplantation, run by XVIVO Perfusion at 15 sites in 8 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 21 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in Germany, United Kingdom, France, Austria, Belgium and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
30 days mortality and 30 days graft dysfunction (time frame: 30 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03991923, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Apr 2026; AzTrials last refreshed its copy on 8 Nov 2026.