Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT03308305 |
| Other study ID # |
2017-1006 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
June 11, 2018 |
| Est. completion date |
May 2025 |
Study information
| Verified date |
November 2023 |
| Source |
Rijnstate Hospital |
| Contact |
Hanneke Keijzer, PhD |
| Phone |
+31 88 005 1979 |
| Email |
hmkeijzer[@]rijnstate.nl |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Rationale: 30-70% of comatose patients admitted to the intensive care unit (ICU) after
cardiac arrest never regain consciousness as a result of post anoxic encephalopathy (PAE).
Early identification of patients without potential for recovery of brain functioning may
prevent inappropriate continuation of medical treatment and improve communication between
doctors and patients. However, current diagnostic and prognostic measures can identify only
20-50% of the patients with irreversible brain damage, precluding cerebral recovery and
awakening. Also, the pathophysiology of brain damage is largely unclear. New magnetic
resonance imaging (MRI) sequences hold potential to substantially improve outcome prediction.
Objectives: 1. To estimate the additional value of early MRI monitoring for the prediction of
neurological outcome of comatose patients after cardiac arrest. 2. To gain insight in the
pathophysiology of PAE by associating MRI findings with histopathological studies of brain
tissue obtained from non-survivors.
Study design: prospective cohort study.
Study population: 100 subsequent comatose patients after cardiac arrest, admitted to the ICU.
Intervention: In addition to standard treatments, patients will undergo MRI of the brain at
day 3, 7, and three months after cardiac arrest. A subgroup of patients will be scanned
within 24 hours after cardiac arrest, to assess feasibility and to gain more insight in the
evolution of brain damage in PAE. Survivors will be followed for one year. Outcome
measurements will focus on disabilities, quality of life, and depression. MRI measures will
be related to outcome.
Main study parameters/endpoints: The primary outcome measure is neurological outcome, defined
as the score on the Cerebral Performance Category (CPC) at six months, dichotomized as good
(CPC 1-2 = no or moderate neurological disability) or poor (CPC 3-5 = severe disability,
coma, or death). Secondary outcome measures include cognitive functioning, depression, and
quality of life at one year, as well as histopathological damage of brain tissue of
non-survivors.
Description:
Standard procedures:
Patients will be monitored and treated according to guidelines for post out of hospital
cardiac arrest treatment as described in local ICU protocols. Patients do not suffer any
harm, disadvantage of discomfort while participating in this study.
Standard treatment includes targeted temperature management, hemodynamic monitoring and
stabilisation, continuous EEG monitoring, blood sampling through the jugular bulb catheter,
Near Infrared Spectroscopy (NIRS), and transcranial doppler (TCD) measurements. The patient's
status is repeatedly assessed and treatment is based on the clinical findings.
Additional procedures:
1. MRI A total of 3 MRI scans is planned for each patient: at day 3 ± 1, and day 7 ± 2
after cardiac arrest, and 3 months ± 2 weeks after cardiac arrest. The imaging protocol
will consist of structural MRI (including FLAIR and ADC maps) to detect ischemic damage,
a 3D T1 for structural analysis and SWI sequences to detect micro bleeds), structural
connectivity measurement by DTI, and functional connectivity measurement by resting
state BOLD functional MRI. Estimated time to prepare the patient and transport to and
from the MRI scanner will be approximately 30 minutes, the scan itself will take
approximately 30 minutes, as well. No intravenous contrast agent is used.
1.1 Acute phase MRI To estimate the feasibility of MRI scanning in the acute phase and
to gain more insight in the dynamics of PAE, a subgroup of patients will be scanned
within 24 hours after cardiac arrest. Patients will be included in this subgroup
dependent on availability of the MRI facility, the clinical stability of the patients
and after the patients legal representatives signed informed consent.
1.2 Transport to the radiology department
The transport to and from the radiology department will be performed as described in the
local protocols on patient transportation. Transport to and from other departments is a
frequent procedure in ICU patients. During transport, the patient will be accompanied by
a physician and ICU nurse. The MRI scans for this project will be handled as 'elective',
which indicates that only patients with a stable hemodynamic and respiratory status will
be transported to and undergo the MRI. For this, a patient has to meet all the following
criteria:
A. Hemodynamic stable condition, defined as:
- mean arterial pressure > 60 mmHg
- no or low inotropes or vasopressors (dosage norepinephrine < 0,3 ug/kg/min and/or
dobutamine < 10 ug/kg/min or equivalent), dosage adjustments less than 0.1
ug/kg/min in the last hour before MRI
B. Stable cardiac rhythm, defined as:
- sinus rhythm 50 - 120 beats per minute
- atrial fibrillation or flutter with ventricle response 60 - 120 per minute
C. Pulmonary stable condition, defined as:
- Arterial oxygen saturation > 95%
- maximum fraction inspired oxygen < 60% with maximum level of positive end
expiratory pressure of 10 cm H2O
- peak inspiratory pressure < 30 cmH2O or <5 l/min oxygen trough nasal cannula (for
patients not on mechanical ventilation)
Mechanical ventilation during transport and scanning will be provided by an MRI
compatible ventilator.
Extensive monitoring of vital functions will not be interrupted during transport or MRI
scanning, by using a mobile trolley with MRI compatible monitoring and ventilation
equipment. At all times, a physician and trained ICU nurse will accompany the patient.
The medical team accompanying the patient can change treatment during transport and
scanning to pursue optimal hemodynamics, pulmonary state, and/or comfort.
1.3 Clinical evaluation of MRI scans All structural MRI scans will be assessed by a
radiologist and results are added to a patient's medical file. Patients and their
families will be informed. However, MRI findings will not be taken into account for
decisions on withdrawal of treatment. BOLD fMRI and DTI data will be analysed later.
2. Outcome At 3 and 6 months, CPC score will be assessed by a telephone interview by a
trained investigator. Additionally, at twelve months, for assessment of cognitive
outcome, depression, quality of life, and care giver strain, the patient will be invited
to the hospital or visited at his / her place of residence. If a patient dies during the
follow-up, the cause of death will be requested from the general practitioner or medical
specialist.
3. Post mortem analysis From all patients that die in the hospital after PAE, permission to
perform autopsy is sought for. Permission will be asked from the legal representative in
the context of current care, after the patient has died. According to current care,
brains will be removed and samples fixated within 24 hours at the local pathology
departments. On samples from 8 brain areas (sensory- and motor cortex, thalamus, basal
ganglia, upper brain stem) evaluation of the agonal state is performed on
hematoxylin-eosin staining. Additionally, predefined sections, including all cortical
layers and white matter, will be formalin fixed for further analyses.
