Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT03881865 |
| Other study ID # |
18/P/088 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
October 8, 2018 |
| Est. completion date |
October 6, 2021 |
Study information
| Verified date |
April 2022 |
| Source |
University Hospital Plymouth NHS Trust |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Study Title:
Early recorded P25/30 somatosensory evoked potentials are associated with neurologic
prognosis of comatose survivors after out of hospital cardiac arrest.
Design:
Prospective, observational, non-interventional, study - prospective collection of data and
interpretation. Analysis of the data and assessment of prognostic value of the P25/30 in
critically ill patients post cardiac arrest.
Study Aims:
To be the first attempt to validate the prognostic potential of early recording [between
24-36 hours post Return Of Spontaneous Circulation] of P25/30 potentials in comatose
survivors who are admitted to a British Intensive care unit after out of hospital cardiac
arrest and who are not treated by hypothermic targeted temperature management.
[Validation of the prognostication significance of P25/30 Somatosensory Evoked Potentials in
predicting neurologic outcome in comatose survivors post out of hospital cardiac arrest].
Outcome Measures:
Primary Endpoint: Neurologic outcome assessed by Cerebral Performance Category score at
hospital discharge.
Secondary endpoints: Mortality at hospital discharge and 28 days [which occurs first],
comparison of prognostic benefit of N20 and P25/30 based multimodal prognostic models.
Population:
Comatose survivors, after out of hospital cardiac arrest, treated in Derriford Hospital ICU,
Penrose and Pencarrow wards.
Eligibility:
Adults [>18 years old], out of hospital cardiac arrest, comatose after Return Of Spontaneous
Circulation, admission to intensive care Estimated Duration:36 months
Description:
Recruitment and Conduction: In the first 24 hours in the Intensive Care Unit [ICU] the
patients will be assessed for eligibility. If they meet the inclusion criteria, their Next Of
Kin will be approached by a member of the study team. An explanation of the study design, the
study protocol and the study objectives, as well as a specific relative information sheet for
the study, will be provided. Meeting with the NOK is done ideally before the SSEP
[SomatoSensory Evoked Potentials] recording or, in case of non-availability of the Next of
kin, after the SSEP recording. The next of kin will have at least 24 hours to decide whether
or not to participate in the study.
N20 and P25/30 SSEP are expected to be recorded and then during the study interpretation of
the results the presence or absence of either or both with the neurological outcome will be
assessed The SSEP recording as a prognostication adjunct after out of hospital cardiac arrest
is part of the usual, established Derriford ICU policy for the management of the comatose
survivors after out of hospital cardiac arrest and is not added or at any way modified,
because of the study. The study purpose is the interpretation of the recording sheet of the
SSEP test in order to answer the question whether the P25/30 potential that is recorded along
with the N20 may have prognostic significance for the patients' neurological outcome. SSEPs
must be recorded between 24-36 hours after ROSC [Return of Spontaneous Circulation]. Mild to
moderate hypothermia ≥35 does not abolish the cortical N20 responses. Median or ulnar nerve
bilaterally will be stimulated. Cortical N20 and P25/30 response is to be described as
bilaterally absent (which is a good predictor of poor neurological outcome), or in other
cases in may be present on one or both sides. If the cortical N20 response is absent, the
presence of the peripheral N9 and N13 response must be present to ensure that the response
has arrived at the cortex. Cervical lesions need to be excluded if Cortical N20 response is
absent. After the SSEP recording, for those patients who informed consent is obtained from
their next of kins and are enrolled to the study, a copy of each recording will be produced
for the study purposes by one member of the study team who is not participating in the
interpretation of the recording. This copy will be anonymised by giving a specific number for
the study. After that, the anonymised copy will become available to the first and to the
second interpreter [both members of the study team (neurophysiology)] who will interpret the
recordings with regards to the presence and absence of the N20 and P25/30 SSEPs and they will
record the results of their interpretation in the results databank. The two interpreters will
be blinded for the personal and the clinical details of the patient. Also each one of the
interpreters will not be aware about the result of the interpretation of the other. The ICU
clinicians will not be aware about the results of the P25/30 interpretation as this will be
part of the study and should not be disclosed to them during the conduction of the study. In
this way, the P25/30 interpretation results will be impossible to affect the treatment of the
patients and / or any of the clinical decisions made about them by the ICU clinicians. In the
unlikely event that there was a discrepancy in interpretation of the SSEP recording between
the two delegated interpreters, then a third member [not a member of the study team] of the
Neurophysiology team would be asked to review the anonymised recording only in order to
decide about the result. As the P25/30 pottential could be generated in the absence of N20 as
they come from two distinct areas of the brain cortex, the presence of either the P25/30 or
the N20 would be confirmed when the amplitude of each one is equal or higher than the
amplitude threshold [0.5 microvolts] used for the analysis of the SSEPs. The presence and the
amplitude of P25/30 will not be dependent on the presence of N20 in the same recording as
each one of them can exist in the absence of the other. Measurement of the amplitude of
recorded P25/30 and N20 and their combinations. Test if there is a correlation of the
recorded amplitudes and their ratio [P25/30 to N20] with the positive predictive value of N20
for the favourable neurological outcome. After the SSEP recording has been conducted, between
24 and 36 hours post ROSC, the patients will be followed up by members of the study team.
Those members of the team will assess the patients, by Cerebral Performance Category and full
neurologic clinical examination, on the day of ICU discharge and on the day of their
discharge from Derriford Hospital. The online system SALUS of Derriford hospital will be used
to follow up the patients after their discharge from ICU and before their discharge from the
hospital. The neurologic outcome, assessed with the Cerebral Performance Category [CPC], will
be recorded. If a study participant died on ICU as a result of severe brain dysfunction or
after the decision of ICU Consultant to be withdrawn from invasive organ support due to
extremely poor prognosis, the discharge CPC would be the most recently recorded, after the
patient have remained consistently off sedation [for a period of time varied for different
sedatives or combination of sedatives]. If a participant died unexpectedly from another cause
rather than severe brain dysfunction, then the most recent CPC before death [if available]
will be recorded as indicative of neurologic outcome for the patients. In case the CPC could
not be assessed, the patient would be excluded from the study analysis. The Results of the
CPC assessment and the outcome of the patients will be stored in the general study databank
for further analysis. At the End of the study, all data will be merged and statistically
analysed and from the result of this analysis one or more relevant manuscripts must be
submitted to a peer-review journal within the first 4 months after the completion of the
study. For each one of the patients-participants, the following clinical data must be
collected prospectively, during the conduction of the study [at different stages i.e. at the
time of enrolment and follow up] and must be kept safely in an anonymised form in a suitable
database. The principles of patients' confidentiality and privacy must be applied at all
times. Age, Gender, Comorbidities, Pre-admission performance status [Assessed by the ECOG/WHO
(Eastern Cooperative Oncology Group/World Health Organisation) performance status score,
Cardiac Arrest Rhythm [Rhythm that was initially recorded after cardiac arrest, usually at
scene], Bystander - witness of cardiac arrest and Cardiopulmonary resuscitation, Anoxic time
[total time between cardiac arrest was noted and ROSC]. If multiple episodes of cardiac
arrest then the sum of all anoxic times to be considered. GCS before intubation [total or
with components if available]. Aetiology of cardiac arrest [cardiac or non-cardiac or
unknown].CT [Computed Tomography] scan report if performed because it was clinically
indicated.Cerebral performance category at ICU discharge and Hospital discharge. Date of
death, number of days post ROSC that death occurred.ICU length of stay, hospital length of
stay.Time of SSEP performed [hours post ROSC].Time between ROSC and ICU admission, First 24
hours post ROSC: mean SaO2 [arterial oxygen saturation], mean PaO2 [arterial partial pressure
of oxygen], mean PaCO2 [arterial partial pressure of carbon dioxide], mean heart rate, mean
blood pressure, mean Glucose levels, mean Lactate levels, mean pH, mean BE, Urea and
Creatinine levels, liver function tests, Plasma sodium levels, Temperature, Sequential Organ
Failure Assessment Score. No particulars tests needed for the study purposes.
The primary outcome measure is the CPC score at hospital discharge with discrete values
ranging from 1 to 5. The score will be dichotomised as 1-2 (positive or good outcome) and 3-5
(negative or poor outcome). Sensitivity, specificity and predictive values of P25/30 in
predicting poor outcome will be computed and the results compared to that of N20. Where
appropriate, parameter estimates will be presented with 95% confidence intervals. Significant
demographic and clinical predictors of poor neurological outcomes will be assessed and
identified using regression models. Statistical data analysis will be undertaken once data
collection from the required number of participants is completed. No interim analysis is
scheduled for this study. Analyses will be performed in SPSS [Statistical Package for the
Social Sciences] version 24 (or later). Sample size calculation was based on diagnostic test
accuracy (adequate sensitivity) of P25/30. Previous studies on patients treated by
hypothermic targeted temperature management showed that the sensitivity of P25/30 in
predicting poor outcome is 90.12% (95% Confidence Interval, 81.5-95.6%). Though the proposed
study will be based on those who are not treated by hypothermic targeted temperature
management, the result (90%) is the 'best' available information regarding pre-determined
sensitivity of P25/30. From experience of the team and analysis of the past three-years pilot
data, the prevalence of poor outcome was assumed to be 75%. In order the maximum marginal
error of estimate does not exceed from 5% with 95% confidence level, and adjusting for
drop-out/lack of consent at 3%, the total required sample size will be 191. No power was
assumed in the calculation of the sample size as there is no testing of hypothesis. Whenever
applicable, a 5% level of significance will be used. As this is not an interventional study,
the chance to terminate the trial is minimal. Spurious and/or missing data will be summarised
and reasons for missingness given where possible. All data analyses will be based on the
complete data only. Statistical analysis of the data will be performed at the end of the
study. If deemed necessary, a separate statistical analysis plan (SAP) can be prepared prior
to the completion of the study and approved by the oversight committee. The study team will
discuss any deviation from the analysis plan and report it to the oversight committee. Any
revisions to the SAP will be documented, including a brief justification and timing of
revision. All eligible participants will be included in the analyses.
All the patients enrolled in the study are expected to be in coma at the time of enrollment.
This is a reality about most of the ICU patients. Therefore, within the first 24 hours after
ICU admission, the members of the study group will discuss with the next of kin of the
patients regarding the potential participation in the study and the informed consent process.
f the participants in the study regain full mental capacity to provide informed consent and
make informed decisions after their enrollment in the study, then the participants will be
fully informed about the study by a member of the study group and they will be asked if they
agree to continue with their participation in the study. If the participants are happy to
remain in the study cohort then their data will be used for analysis and publication
purposes. If the participants decide anytime to withdraw from the study then their decision
will be respected but it will be explained that that their data already collected may still
be analysed as part of the study. The same options will be available for the next of kin that
would have consented initially for the participation of patients in the study.
