Cardiac Arrest With Successful ResuscitationNCT01960699
Proteomic Profiling to Reveal Novel Prognostic Markers for Neurological Outcome Following Resuscitation
An observational study of Cardiac Arrest With Successful Resuscitation, run by Medical University of Vienna at 1 site in Austria.
Trial summary
Background: Cardiac arrest is a life-threatening event. Intensivists are challenged with an increasing number of patients with uncertain neurological outcome following cardiopulmonary resuscitation (CPR). The prognostic value of current biomarkers for neurophysiologic long-term outcome is limited. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Cardiac Arrest With Successful Resuscitation
- How many people
- 96 participants
- Where
- 1 siteAustria
- Study dates
- Oct 2013to Jan 2020
- How long will I take part?
- 3 Years
- Phase
- Observational
- Are there results?
- None posted in the registry
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 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Resuscitated patients
Who may be able to join
- Nontraumatic, normothermic cardiac arrest due to cardiac disorders, respiratory failures, or hemodynamic or metabolic factors.
- A Glasgow Coma Scale of 3, none of the patients will be conscious at the time of hospital admission.
- No previous cardiac arrest, as well as known or coexisting neurological disorders or neoplasms of the central nervous system.
- No history of psychiatric illness, no alcohol or drug dependency, and no psychotropic medication.
- Initiation of mild therapeutic hypothermia
Who cannot join
- hydrocephalus and shunt artifact
- severe movement artifacts
- intracerebral hemorrhage
- old large ischemic lesion
Trial locations and contacts
1 site in 1 country.
About this study
Background: Cardiac arrest is a life-threatening event. Intensivists are challenged with an increasing number of patients with uncertain neurological outcome following cardiopulmonary resuscitation (CPR). The prognostic value of current biomarkers for neurophysiologic long-term outcome is limited.
Hypothesis: We hypothesize that specific brain-derived tissue leakage proteins can be identified to reveal novel, more reliable prognostic biomarkers for good neurological outcome.
Read more
Methods: This translational study (n=100) is a combination of a prospective basic science study intended to reduce the number of potential plasma biomarker candidates by proteomic shotgun analyses in brain tissue autopsy samples and plasma samples from resuscitated patients (n=10) and a prospective clinical validation study in a large study population (n=90) by high-throughput analyses. Selection of proteomic markers and signature estimation will be performed to discriminate patients with good and poor outcome.
Clinical perspective: A structured proteomic analysis approach might identify the best marker out of all proteins liberated during cellular damage.
Read the detailed description
Background: Cardiac arrest is a life-threatening event. Intensivists are challenged with an increasing number of patients with uncertain neurological outcome following cardiopulmonary resuscitation (CPR). The prognostic value of current biomarkers for neurophysiologic long-term outcome is limited. Therefore, identification of novel plasma markers with higher predictive value for neurophysiological recovery is critical for patient management after CPR.
Hypothesis: We hypothesize that specific brain-derived tissue leakage proteins can be identified to reveal novel, more reliable prognostic biomarkers for good neurological outcome.
Methods: This translational study (n=100) is a combination of a prospective basic science study intended to reduce the number of potential plasma biomarker candidates by proteomic shotgun analyses in brain tissue autopsy samples and plasma samples from resuscitated patients (n=10) and a prospective clinical validation study in a large study population (n=90) by high-throughput analyses. Samples will be analyzed by proteomic shotgun analyses using the Q-Exactive quadrupole-orbitrap mass spectrometer (MS). MS/MS data will be interpreted by the MaxQuant and Perseus Software. In order to identify brain-derived proteins within plasma, the plasma proteome of 10 resuscitated patients will be compared to the proteomic profile of brain tissue. This will reduce the number of potential plasma biomarker candidates associated with neurologic outcome. The prospective validation in plasma samples will be performed by a targeted proteomics approach using selected reaction monitoring (SRM) on a triple quadrupole ion MS. Neurological outcome will be assessed by the five-point scale (death, persistent vegetative state, severe disability, moderate disability, and good recovery) according to the cerebral performance categories (CPC). A CPC sore of <3 is considered a good neurological outcome. Selection of proteomic markers and signature estimation will be performed by L1 regularized logistic regression, where the tuning parameter will be optimized by cross-validated model performance. The signature's ability to discriminate patients with good and poor outcome will be described by ROC analysis.
Clinical perspective: An accurate predictor of neurological outcome following CPR is of utmost clinical importance. However, previous studies focused on a very limited array of biomarkers. Therefore, a structured proteomic analysis approach might identify the best marker out of all proteins liberated during cellular damage.
- Keywords
- Prognosis, Neurological outcome, Resuscitation, Biomarker
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| CPC < 3 | Good neurological outcome | |
| CPC >/= 3 | Unvavourable neurologic outcome |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cerebral performance categories (CPC)of <3
Measured: participants will be followed for the duration of intensive-care unit stay, an expected average of 2 weeks.
Secondary outcomes (1)
Cerebral performance categories (CPC)of <3
Measured: 6 Months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Oct 2013 (estimated)
- Study startOct 2013
- Primary completionJan 2020
- Study completionJan 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Cardiac Arrest With Successful ResuscitationStudies of the same condition, open and under way.
- More trials run by Medical University of ViennaThe sponsor's other registered studies.
- 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 96 participants (actual)
- Target duration
- 3 Years
Sponsor and investigators
- Lead sponsor
- Medical University of Vienna
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Christopher Adlbrecht, Medical University of Vienna
- Investigators
- Christopher Adlbrecht, MD, Principal investigator, Medical University of Vienna
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01960699
- Sponsor's protocol ID
- EK_Nr_1740/2013
- Status last verified
- Feb 2020
- First submitted
- 8 Oct 2013
- Last updated
- 24 Feb 2020
- Results posted
- No
- Data monitoring committee
- No
Publications
Distelmaier K, Muqaku B, Wurm R, Arfsten H, Seidel S, Kovacs GG, Mayer RL, Szekeres T, Wallisch C, Hubner P, Goliasch G, Heinze G, Heinz G, Sterz F, Gerner C, Adlbrecht C. Proteomics-Enriched Prediction Model for Poor Neurologic Outcome in Cardiac Arrest Survivors. Crit Care Med. 2020 Feb;48(2):167-175. doi: 10.1097/CCM.0000000000004105.
PubMed 31939784
Study at a glance
From the registry record, last updated by the sponsor on 24 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Proteomic Profiling to Reveal Novel Prognostic Markers for Neurological Outcome Following Resuscitation
- ClinicalTrials.gov ID
- NCT01960699
- Acronym / sponsor ID
- EK_Nr_1740/2013
- Keywords
- Prognosis, Neurological outcome, Resuscitation, Biomarker
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 96 participants (actual)
- Lead sponsor
- Medical University of ViennaUniversity, hospital or other
- Study start
- Oct 2013 (actual)
- Primary completion
- Jan 2020 (actual)
- Study completion
- Jan 2020 (actual)
- First posted
- 11 Oct 2013 (estimated)
- 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.
Background: Cardiac arrest is a life-threatening event. Intensivists are challenged with an increasing number of patients with uncertain neurological outcome following cardiopulmonary resuscitation (CPR). The prognostic value of current biomarkers for neurophysiologic long-term outcome is limited.
Hypothesis: We hypothesize that specific brain-derived tissue leakage proteins can be identified to reveal novel, more reliable prognostic biomarkers for good neurological outcome.
Methods: This translational study (n=100) is a combination of a prospective basic science study intended to reduce the number of potential plasma biomarker candidates by proteomic shotgun analyses in brain tissue autopsy samples and plasma samples from resuscitated patients (n=10) and a prospective clinical validation study in a large study population (n=90) by high-throughput analyses. Selection of proteomic markers and signature estimation will be performed to discriminate patients with good and poor outcome.
Clinical perspective: A structured proteomic analysis approach might identify the best marker out of all proteins liberated during cellular damage.
Detailed description
Background: Cardiac arrest is a life-threatening event. Intensivists are challenged with an increasing number of patients with uncertain neurological outcome following cardiopulmonary resuscitation (CPR). The prognostic value of current biomarkers for neurophysiologic long-term outcome is limited. Therefore, identification of novel plasma markers with higher predictive value for neurophysiological recovery is critical for patient management after CPR.
Hypothesis: We hypothesize that specific brain-derived tissue leakage proteins can be identified to reveal novel, more reliable prognostic biomarkers for good neurological outcome.
Methods: This translational study (n=100) is a combination of a prospective basic science study intended to reduce the number of potential plasma biomarker candidates by proteomic shotgun analyses in brain tissue autopsy samples and plasma samples from resuscitated patients (n=10) and a prospective clinical validation study in a large study population (n=90) by high-throughput analyses. Samples will be analyzed by proteomic shotgun analyses using the Q-Exactive quadrupole-orbitrap mass spectrometer (MS). MS/MS data will be interpreted by the MaxQuant and Perseus Software. In order to identify brain-derived proteins within plasma, the plasma proteome of 10 resuscitated patients will be compared to the proteomic profile of brain tissue. This will reduce the number of potential plasma biomarker candidates associated with neurologic outcome. The prospective validation in plasma samples will be performed by a targeted proteomics approach using selected reaction monitoring (SRM) on a triple quadrupole ion MS. Neurological outcome will be assessed by the five-point scale (death, persistent vegetative state, severe disability, moderate disability, and good recovery) according to the cerebral performance categories (CPC). A CPC sore of <3 is considered a good neurological outcome. Selection of proteomic markers and signature estimation will be performed by L1 regularized logistic regression, where the tuning parameter will be optimized by cross-validated model performance. The signature's ability to discriminate patients with good and poor outcome will be described by ROC analysis.
Clinical perspective: An accurate predictor of neurological outcome following CPR is of utmost clinical importance. However, previous studies focused on a very limited array of biomarkers. Therefore, a structured proteomic analysis approach might identify the best marker out of all proteins liberated during cellular damage.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 3 Years
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| CPC < 3 | – | –Good neurological outcome |
| CPC >/= 3 | – | –Unvavourable neurologic outcome |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Resuscitated patients
Key inclusion criteria (5 listed)
- Nontraumatic, normothermic cardiac arrest due to cardiac disorders, respiratory failures, or hemodynamic or metabolic factors.
- A Glasgow Coma Scale of 3, none of the patients will be conscious at the time of hospital admission.
- No previous cardiac arrest, as well as known or coexisting neurological disorders or neoplasms of the central nervous system.
- No history of psychiatric illness, no alcohol or drug dependency, and no psychotropic medication.
- Initiation of mild therapeutic hypothermia
Key exclusion criteria (4 listed)
- hydrocephalus and shunt artifact
- severe movement artifacts
- intracerebral hemorrhage
- old large ischemic lesion
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Cerebral performance categories (CPC)of <3
Time frame: participants will be followed for the duration of intensive-care unit stay, an expected average of 2 weeks.
1 secondary outcome
Cerebral performance categories (CPC)of <3
Time frame: 6 Months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Feb 2020.
- Results publication: PubMed 31939784Distelmaier K, Muqaku B, Wurm R, Arfsten H, Seidel S, Kovacs GG, Mayer RL, Szekeres T, Wallisch C, Hubner P, Goliasch G, Heinze G, Heinz G, Sterz F, Gerner C, Adlbrecht C. Proteomics-Enriched Prediction Model for Poor Neurologic Outcome in Cardiac Arrest Survivors. Crit Care Med. 2020 Feb;48(2):167-175. doi: 10.1097/CCM.0000000000004105.
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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.
Christopher Adlbrecht, MD principal investigator
Medical University of Vienna
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Cardiac Arrest With Successful Resuscitation, run by Medical University of Vienna at 1 site in Austria.
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 5 inclusion and 4 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: finished, as of the sponsor's last update on 24 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Austria. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Cerebral performance categories (CPC)of <3 (time frame: participants will be followed for the duration of intensive-care unit stay, an expected average of 2 weeks.). 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 NCT01960699, which also lists 1 linked publication.
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 24 Feb 2020.