Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT04876222 |
| Other study ID # |
DISCO-no-COMA |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
May 3, 2021 |
| Est. completion date |
May 1, 2027 |
Study information
| Verified date |
October 2023 |
| Source |
Aarhus University Hospital Skejby |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
In patients with Out-of-Hospital Cardiac arrest who achieves Return Of Spontaneous
Circulation (ROSC) The investigators want to evaluate whether there is a benefit from acute
Angiography compared to subacute (12-24 hours) Angiography
Description:
Background: The majority of patients with out-of-hospital cardiac arrest (OHCA) have ischemic
heart disease (IHD). If signs of ST-elevation myocardial infarction (STEMI) acute coronary
angiography (CAG) and primary percutaneous coronary intervention (PPCI) is recommended. In
most cases, patients with OHCA who does not achieve Return Of Spontaneous Circulation (ROSC)
are also triaged directly to a tertiary center with the possibility to establish mechanical
circulatory support, e.g. Extracorporeal Cardiopulmonary Resuscitation (eCPR) (Figure 1). For
the remaining group of patients with OHCA who achieves ROSC and have no signs of STEMI it is
unsettled whether there is a benefit of acute CAG.
A large international study (Direct or Subacute COronary angiography in out-of-hospital
cardiac arrest - DISCO) from Uppsala, Sweden, will study the role of acute CAG in 1006
patients with OHCA who are comatose after achieving ROSC (2). In the Swedish study they only
include comatose patients, and randomize patients to either acute CAG or CAG after 3 days.
Three of four Danish tertiary centers have decided to join the Swedish DISCO-study (From now
on named DISCO-MAIN).
However, many OHCA patients are not comatose, and without signs of STEMI, thus not eligible
for DISCO-MAIN. The investigators also want to investigate the role of acute CAG in these
patients, which is the purpose of the current study, named DISCO-no-COMA (Direct or subacute
coronary angiography in patients with out-of-hospital-cardiac arrest who are not comatose).
This study will include patients in parallel with the DISCO-MAIN-study. This means that all
patients with OHCA who receive ROSC and do not fulfill the criteria for acute CAG (STEMI) can
be randomized in either DISCO-MAIN (if comatose) or DISCO-no-COMA (if not comatose).
This means that a patient with OHCA without obvious non-cardiac cause, should be triaged as
follows (See figure 1):
1. ROSC not achieved (ongoing CardioPulmonary Resuscitation (CPR)): These patients are
triaged directly to the catheterization laboratory with the possibility to establish
ECPR treatment (5) and perform CAG/PCI (percutaneous coronary intervention) and implant
pacemaker if indicated.
2. Signs of STEMI: These patients are triaged directly for acute CAG according to
guidelines (6).
3. ROSC, COMA (Glasgow coma scale <=8), not STEMI: Should be included in the DISCO-MAIN
trial.
4. ROSC, Glasgow coma scale >8, not STEMI: Should be included in the DISCO-no-COMA trial.
Purpose:
To randomize non-comatose (Glasgow coma scale >8) OHCA survivors for acute CAG or subacute
CAG (after 12-24 hours).
Study period: 1.5.2021 to 1.5.2026.
Centers eligible for participation: Danish and European centers. The investigators will
primarily contact centers already participating in the DISCO-MAIN trial. Currently all four
Danish Tertiary centers participate and up to 8 centers from the Netherlands have agreed to
participate.
Patients are randomized to:
Group A: Acute CAG: The patient is triaged directly to the catheterization laboratory for
acute evaluation including Echocardiography (ECHO), acute CAG and PCI if indicated according
to guidelines.
Group B: Subacute CAG: The patient is triaged to the coronary care unit (CCU) for rhythm
surveillance, and additional diagnostics, and in case there is found indication for CAG, it
is planned for the coming day in daytime (12-24 hours after cardiac arrest).
Revascularization is performed if indicated according to guidelines.
Revascularization in group A and B:
The goal is to perform revascularization of the culprit lesion. Additional lesions will be
scheduled for an elective procedure, typically after 3-4 weeks. If Coronary Artery Bypass
Grafting (CABG) is indicated, it will be scheduled according to the centers local routine.
Cross-over:
A patient randomized to group B will be scheduled for acute CAG if:
1. Signs of STEMI (acute CAG mandatory).
2. Persistent hemodynamic instability of more than 1 hour after randomization, defined as:
need of increased dose of vasopressor/inotropic, low Left ventricular ejection fraction
(LVEF), no clearance of lactate (Acute CAG should be considered)
3. Recurrent cardiac arrest (Acute CAG should be considered)
4. Patients who after admission is judged to have NSTEMI can cross-over to acute CAG if
they are not stabilized medically.
Statistics: Data is analysed according to intention-to-treat. Continuous data will be
presented as mean ± standard deviation, and comparison made using t-test if normally
distributed. Non-normal distributed data will be presented as median [interquartile range],
and compared using Mann Whitney U-test. Categorical variables are compared using Fischers
exact test or Chi square test as appropriate, and presented as numbers and per centages.
Significans level is p< 0.05 (two-sided).
Data management: Data will be collected and stored according to the Danish Privacy Law. The
E-CRF (Electronic Case Report Form) is computer-based (TrialPartner). Patient and procedure
information will be entered in the E-CRF by the study nurses at each site. Date is also
collected from the CPR-register, the Danish National Patient Register (LPR-register), as well
as the invasive registries covering procedure related data for all patients who have CAG or
PCI performed. TrialPartner is approved according to Danish regulative, and all access and
data-entry are logged. When the study is finalized and data from the various registries have
been merged, the personal identification number is removed, and all cases are assigned a key.
A separate key file is store. Data is then made anonymous.
Inclusion of patients and consent:
All patients with OHCA without obvious non-cardiac cause are triaged to the invasive centers.
The physician on call ensures that any patient with STEMI or ongoing CPR are triaged directly
to the catheterization laboratory. Remaining patients are included in the DISCO-MAIN study if
comatose. Non-comatose patients are included in the present DISCO-no-COMA study. They are
included according to the paragraph "Research in acute situations", and are randomized when
they are still in the prehospital phase if possible, en route to the hospital. After arrival
to the hospital, the investigators will inform the patient further, to achieve written
informed consent also.
Ethical aspects:
The investigators believe it is legitimate to randomize patients to acute or subacute CAG
because Denmark nationally have centers that adhere to both strategies, and it is uncertain
whether there is a benefit from acute CAG in OHCA patients who have achieved ROSC and are
without signs of obvious STEMI.
Furthermore, there are clear recommendations when to cross-over if randomized to a
conservative strategy.
Withdrawal from the study: The patients can at any point, and without any reason, decide not
to participate in the study. The patient will be asked if data collected from randomization
and until withdrawal may be used. Otherwise data will be deleted. Reason for withdrawal, and
the patient's decision whether data can be used or not, will be filled in the electronic
health record.
Biobank / biological material: No biobank is collected at present.
Blinding: The study is not blinded, which seems impossible to do.
Personal data:
The national Privacy Law will be followed. The trial will be filed to the Central Denmark
Region (Instead of the Danish Data Protection Agency, according to current practice), to the
Ethical Committee in the Central Denmark Region and to Clinicaltrials.gov. The National Board
of Health will be aplied for access to data from the CPR-register and the National Patient
Register.
Access to data: Data will be stored in TrialPartner. Any access or attempt to access will be
logged. Investigator/institution will grant access for monitoring and audit also from the
ethical committee. Investigator will be responsible and ensure that any patient has given
written consent, or a deputy consent has been achieved according to the rules for research in
acute situations.
Endpoint committee: An endpoint committee will be established consisting of a cardiologist
and an anesthesiologist who validates all clinical endpoints, and establish the final
diagnosis (cause of cardiac arrest) for the patient. They will have access to all study
material as well as information from patient health records if necessary.
Coordinating center: The research department at the Department of cardiology, Aarhus
University hospital, will be the coordinating center, and responsible for establishing the
eCRF, collecting data, coordinating safety and endpoint committee meetings, and publish data.
Monitoring: Aarhus University hospital will be responsible for trial monitoring. Study nurses
will visit each hospital when initiating the trial, and then approximately two times during
the study. The monitoring visits will as in the DISCO-MAIN trial focus on: a) That the study
adheres to the protocol, b) that inclusion of patients is according to protocol and inclusion
criteria, c) that the correct data is entered in the ECRF, and d) that necessary resources
are available locally to perform the study.
Economy: The investigators will apply private funds for support to the study. The responsible
physicians will receive no honorarium.
Publications: All results, positive and negative or inconclusive will be published.
Power calculation:
There are limited data on mortality, and risk of recurrent cardiac arrest or cardiogenic
shock, in patients without coma who have achieved ROSC after OHCA and just waits for CAG. In
previous studies the 30-day mortality was 34% in patients with Acute Myocardial Infarction
(AMI) who had Ventricular Tachycardia (VT) or Ventricular Fibrillation (VF) (7), the risk of
cardiogenic shock was 9% in patients with VT and 27% in patients with VF (8), and the risk of
recurrent cardiac arrest was 7% within 48 hours (8). In the light of competing risks, and in
the light of a general reduction in case-fatality during the years, it is assumed that the
risk of the combined endpoint (MACE) is approximately 30% within 30 days of randomization.
With an alfa of 0.05, and power of 80%, it will be possible to document a difference in MACE
of 25% if 1080 patients are included. With an expected drop-out of 10% the aim is to include
1200 patients.
