Clinical Trial Details
— Status: Terminated
Administrative data
| NCT number |
NCT05243914 |
| Other study ID # |
STUDY00000230 |
| Secondary ID |
|
| Status |
Terminated |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
January 21, 2022 |
| Est. completion date |
January 3, 2024 |
Study information
| Verified date |
March 2024 |
| Source |
University of Arizona |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational [Patient Registry]
|
Clinical Trial Summary
This is a prospective, observational, pilot trial to evaluate the feasibility of heart
transplantation using normothermic regional perfusion (NRP) donation after donor circulatory
death (DCD). Adults who meet standard criteria for heart transplantation listing and
study-specific eligibility criteria will enroll in the study.
the investigators anticipate evaluating an initial cohort of approximately 100 DCD donors for
a final yield of 40 hearts. The investigators will accept donors between the ages of 18 and
65 who are determined to have heart function/quality appropriate for donation for
transplantation based on available donor data and testing.
If feasible, donors might be relocated to BUMCP to maintain uniformity of process, minimize
cold ischemic time, and allow for more rapid and improved communication during the initial
pilot phase.
Recipients will be selected based on blood group, crossmatch, size match, and clinical
stability per standard allocation practices. Recipients will be followed post-transplantation
per BUMCP Heart Transplant standard protocol.
Description:
The surgical management of end-stage heart failure generally falls into two categories:
mechanical circulatory support and heart transplantation. The availability of suitable organs
intrinsically limits the rate of heart transplantation. The vast majority of cadaveric donor
hearts are obtained from patients who have had irreversible cessation of neurological
function (DBD - Donation after Brain Death). Recently, there has been renewed interest in the
possibility of obtaining cadaveric hearts from DCD (Donation after Circulatory Death) donors
who have had irreversible cessation of cardiopulmonary function. In contrast to DBD, DCD
involves the intentional withdrawal of life support measures to allow controlled circulatory
death to occur. If the patient fails to progress to circulatory death within the allotted
time, DCD donation is terminated, and the patient is placed on comfort measures until they
expire.
The concept of DCD heart transplantation is not new. Barnard used DCD hearts in his early
series of heart transplants because the idea of brain death had not yet been well
established. Clinical DCD heart transplant programs have been established in the UK, Belgium,
and Australia. However, DCD heart transplantation currently remains virtually nonexistent in
the US. DCD can increase the available US heart donor pool by as much as 20%. Of the more
than 41,000 adult heart transplants performed in the US over the past 20 years, only 4 have
been from DCD donors. Perhaps understandably, there is some hesitance in using a donor heart
that has just undergone circulatory death.
Potential DCD donors are stratified according to the Maastricht classification system: 1)
dead on arrival at the hospital, 2) out-of-hospital arrest with unsuccessful resuscitation,
3) circulatory arrest as a result of a planned withdrawal of life support, 4) circulatory
arrest in a patient who is already brain-dead, and 5) circulatory arrest while in the
hospital with unsuccessful resuscitation. Categories 1, 2, and 5 would be considered
"uncontrolled" DCD. Categories 3 and 4 are considered "controlled" DCD, where the duration
and conditions of warm ischemia are known, and the precise course of circulatory arrest can
be followed.
The current procedure of DCD organ donation and procurement follows a well-established course
for lung, liver, kidney, and pancreas transplantation in the United States. After consent has
been obtained, the organs are allocated through the United Network of Organ Sharing (UNOS).
When all parties are present and ready, the donor is withdrawn from life support (i.e.,
discontinuation of mechanical ventilation and any vasoactive medications). The surgical teams
are generally present on the premises but not at the donor's bedside. After circulatory
arrest occurs, which is determined by the absence of pulse and organized rhythmic cardiac
activity, death is declared by a physician not associated with the transplant teams.
Subsequently, a standoff period is observed (5 minutes) to ensure a complete cessation of the
circulation before organ procurement is commenced. If after withdrawal of life support, the
patient does not progress to circulatory death within the allotted time (variable among
hospitals, but 60 minutes in this study), the procurement is abandoned, and the patient is
transferred out of the operating room and placed on palliative measures.
Given that DCD organ donation is already currently practiced in the US, the same standard
approach defined by each state and locality can also be applied to DCD heart donation.
However, this protocol will utilize a normothermic regional perfusion (NRP) strategy that
involves the re-establishment of circulatory blood flow after the period of circulatory
arrest has been established and the 5 minutes of standoff time has passed. The local Organ
Procurement Organization (Donor Network of Arizona-DNAZ) and BUMCP Leadership have reviewed
and approved this approach to DCD heart donation. Specifically, normothermic regional
perfusion involves the following steps:
1. Opening the chest through a standard sternotomy used for heart and lung procurement.
2. Ligation of all the blood vessels that supply blood to the brain to ensure that blood
flow to the brain is not re-established once circulation is restarted, as described
below.
3. Standard cannulation of the aorta and the right atrium as is done for cardiac surgical
procedures.
4. Initiation of cardiopulmonary bypass, which will re-establish blood flow to all organs
of the body, including the heart under normothermia. The initial step for ligation of
the blood vessels to the head is necessary to ensure that blood flow to the brain does
not occur.
Once blood flow to the heart is established, the heart will start beating. At 30 to 60-minute
intervals, the donor will be separated from cardiopulmonary bypass, and the heart will be
assessed for functionality. If accepted, standard DBD procurement will commence. The heart
transplantation surgery on the potential recipient will only begin once the heart has been
accepted as suitable.
If, after assessment, the heart is not suitable, cardiopulmonary bypass will be restarted.
The donor heart will be reassessed at 30-minute intervals up to 180 minutes. If no
significant acceptable recovery occurs and the heart is not deemed suitable for
transplantation, then the study will be terminated, but the remaining organs can be recovered
as standard practice.
Although there has been limited experience with DCD heart donation in the US up to this
point, they are being performed with increasing frequency in Europe and Australia. Although
protocols already exist for DCD donation for other organs, there is currently no established
US consensus for DCD hearts.
To date researchers have found comparable short-term and midterm results between the standard
and DCD heart transplantation techniques, however the longer-term results are unknown at this
time. This study will help us learn more about the long-term outcomes and see how well the
DCD technique works for heart transplant.
Although the investigators report comparable short-term and midterm results between DBD and
DCD heart transplantation, the longer-term results are unknown Regardless of the retrieval
protocol utilized, there is now sufficient accumulated clinical experience to indicate that
heart transplants from selected DCD donors are associated with outcomes comparable to those
observed with DBD donors.
