Cardiac ArrestNCT03539497
Prognostic Value of Plasma Mitochondrial DNA and Cytochrome C After Cardiac Arrest
An observational study of Cardiac Arrest, run by University Medical Centre Ljubljana at 1 site in Slovenia.
Trial summary
The aim of the study is to determine prognostic value of plasma mitochondrial DNA and cytochrome C after cardiac arrest. The study will be conducted in three parts: 1. Determine plasma concentrations of mitochondrial DNA and cytochrome C in healthy population. 2. Read more about this study
- Who is it for?
- Ages 14 years and older
- Conditions the study is for
- Cardiac Arrest
- What is being tested?
- Biomarker
- How many people
- 87 participants
- Where
- 1 siteSlovenia
- Study dates
- 8 Jan 2019to 30 Mar 2024
- 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 14 years and older
- All sexes
- Child, Adult, Older adult
Study population: Unconscious patients after cardiac arrest treated with therapeutic hypothermia.
Who may be able to join
- unconscious after cardiac arrest
- therapeutic hypothermia
Who cannot join
- expected survival less than 24h
Trial locations and contacts
1 site in 1 country.
Slovenia1 site
University Medical Centre Ljubljana, Ljubljana, Slovenia
Ljubljana, 1000
About this study
The aim of the study is to determine prognostic value of plasma mitochondrial DNA and cytochrome C after cardiac arrest.
The study will be conducted in three parts:
- Determine plasma concentrations of mitochondrial DNA and cytochrome C in healthy population.
- Determine release profile of mitochondrial DNA and cytochrome C to plasma after cardiac arrest.
- Determine plasma prognostic value of mitochondrial DNA and cytochrome C after cardiac arrest and compare it with established prognostic methods.
Read the detailed description
Scientific background
Cardiac arrest is one of leading causes of mortality in developed world. Survival ranges between 15 and 22%. Patients surviving cardiac arrest can have significant neurological impairment. None of currently available diagnostic methods can detect neurological consequences in early post resuscitation period. Biomarkers (NSE - neuron specific enolase, protein S100, GFAP - glial fibrillary acidic protein), imaging (computer tomography, magnetic resonance imaging) and functional studies (EEG - electro encephalography, SSEP - somatosensory evoked potentials) have all shown only limited prognostic value in predicting survival with good neurological outcome after cardiac arrest.
Mitochondrial damage is one of key mechanisms of postresuscitation dysfunction. Elevated values of mitochondrial damage-associated molecular patterns were already linked to worst survival after cardiac arrest and critical illness.
Mitochondrial damage often results in cell death and mitochondrial damage-associated molecular patterns are released into bloodstream. Mitochondrial damage-associated molecular patterns that can be detected in serum or plasma are: mitochondrial DNA, mitochondrial transcription factor A, N-formyl peptides, succinate, cardiolipin, cytochrome C...
With a more sensitive method of early neuroprognostication after cardiac arrest the limited medical resources could be used more effectively in patients with chance of good neurological recovery.
Aim of the study
The aim of this study is to research the role of mitochondrial damage-associated molecular patterns in patients after cardiac arrest.
- Determine normal plasma values of mitochondrial damage-associated molecular patterns in healthy population.
- Compare current prognostic procedures of post-resuscitation neurological damage with prognostic value of mitochondrial DNA and cytochrome C in plasma.
Expected results
Due to central role of mitochondria in hypoxic-ischemic tissue damage a greater mitochondrial damage (measured trough release of mitochondrial damage-associated molecular patterns) is expected to have direct correlation with extent of tissue damage (also neurological). Currently published data indicate that patients with higher plasma mitochondrial DNA levels after cardiac arrest have higher mortality. Correlation of mitochondrial damage-associated molecular patterns to extent of neurological damage in survivors of cardiac arrest was not researched yet.
Methods
- Measurement of measure mitochondrial damage-associated molecular patterns in healthy population (mitochondrial DNA and cytochrome C).
- Determination of releasing profile of mitochondrial DNA and cytochrome C in survivors of cardiac arrest and establishment of best sample collection time.
- Calculation of predictive value for survival of cardiac arrest with good neurological outcome for mitochondrial DNA and cytochrome C.
Mitochondrial damage-associated molecular patterns will be measured in samples of plasma. Mitochondrial DNA will be measured using PCR method. Cytochrome C will be measured using ELISA.
- Conditions
- Cardiac Arrest
- Being tested
- Biomarker
- Keywords
- biomarker
- Medical subject headings
- Heart Arrest
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BiomarkerDiagnostic test
Plasma mitochondrial DNA, plasma Cytochrome C
What is being measured
The primary outcome is the main question the study is designed to answer.
Correlation of plasma mitochondrial DNA and cytochrome C with survival with good neurological outcome (CPC 1 and 2) at hospital discharge
Relationship between plasma mitochondrial DNA and cytochrome C with neurological damage after cardiac arrest
Measured: In hospital mortality, 30days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 May 2018
- Study start8 Jan 2019
- Primary completion23 Aug 2023
- Study completion30 Mar 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Cardiac ArrestStudies of the same condition, open and under way.
- More trials run by University Medical Centre LjubljanaThe 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
- 87 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Medical Centre Ljubljana
- Sponsor type
- University, hospital or other
- Collaborators
- University of Ljubljana
- Responsible party
- Principal investigator, Peter Radsel, University Medical Centre Ljubljana
- Investigators
- Marko Noč, MD, Study chair, UMC Ljubljana
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03539497
- Sponsor's protocol ID
- UKC-KOIIM-c-arrest
- Status last verified
- Dec 2023
- First submitted
- 24 Mar 2018
- Last updated
- 6 Dec 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Greer DM, Rosenthal ES, Wu O. Neuroprognostication of hypoxic-ischaemic coma in the therapeutic hypothermia era. Nat Rev Neurol. 2014 Apr;10(4):190-203. doi: 10.1038/nrneurol.2014.36. Epub 2014 Mar 11.
PubMed 24614515Girotra S, Chan PS, Bradley SM. Post-resuscitation care following out-of-hospital and in-hospital cardiac arrest. Heart. 2015 Dec;101(24):1943-9. doi: 10.1136/heartjnl-2015-307450. Epub 2015 Sep 18.
PubMed 26385451Arnalich F, Codoceo R, Lopez-Collazo E, Montiel C. Circulating cell-free mitochondrial DNA: a better early prognostic marker in patients with out-of-hospital cardiac arrest. Resuscitation. 2012 Jul;83(7):e162-3. doi: 10.1016/j.resuscitation.2012.03.032. Epub 2012 Apr 7. No abstract available.
PubMed 22490673Rodrigues Filho EM, Ikuta N, Simon D, Regner AP. Prognostic value of circulating DNA levels in critically ill and trauma patients. Rev Bras Ter Intensiva. 2014 Jul-Sep;26(3):305-12. doi: 10.5935/0103-507x.20140043.
PubMed 25295826Nakahira K, Hisata S, Choi AM. The Roles of Mitochondrial Damage-Associated Molecular Patterns in Diseases. Antioxid Redox Signal. 2015 Dec 10;23(17):1329-50. doi: 10.1089/ars.2015.6407. Epub 2015 Aug 17.
PubMed 26067258
Study at a glance
From the registry record, last updated by the sponsor on 6 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prognostic Value of Plasma Mitochondrial DNA and Cytochrome C After Cardiac Arrest
- ClinicalTrials.gov ID
- NCT03539497
- Acronym / sponsor ID
- UKC-KOIIM-c-arrest
- Conditions
- Cardiac Arrest
- Keywords
- biomarker
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 87 participants (actual)
- Lead sponsor
- University Medical Centre LjubljanaUniversity, hospital or other
- Collaborators
- University of Ljubljana
- Study start
- 8 Jan 2019 (actual)
- Primary completion
- 23 Aug 2023 (actual)
- Study completion
- 30 Mar 2024 (estimated)
- First posted
- 29 May 2018 (actual)
- 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.
The aim of the study is to determine prognostic value of plasma mitochondrial DNA and cytochrome C after cardiac arrest.
The study will be conducted in three parts:
- Determine plasma concentrations of mitochondrial DNA and cytochrome C in healthy population.
- Determine release profile of mitochondrial DNA and cytochrome C to plasma after cardiac arrest.
- Determine plasma prognostic value of mitochondrial DNA and cytochrome C after cardiac arrest and compare it with established prognostic methods.
Detailed description
Scientific background
Cardiac arrest is one of leading causes of mortality in developed world. Survival ranges between 15 and 22%. Patients surviving cardiac arrest can have significant neurological impairment. None of currently available diagnostic methods can detect neurological consequences in early post resuscitation period. Biomarkers (NSE - neuron specific enolase, protein S100, GFAP - glial fibrillary acidic protein), imaging (computer tomography, magnetic resonance imaging) and functional studies (EEG - electro encephalography, SSEP - somatosensory evoked potentials) have all shown only limited prognostic value in predicting survival with good neurological outcome after cardiac arrest.
Mitochondrial damage is one of key mechanisms of postresuscitation dysfunction. Elevated values of mitochondrial damage-associated molecular patterns were already linked to worst survival after cardiac arrest and critical illness.
Mitochondrial damage often results in cell death and mitochondrial damage-associated molecular patterns are released into bloodstream. Mitochondrial damage-associated molecular patterns that can be detected in serum or plasma are: mitochondrial DNA, mitochondrial transcription factor A, N-formyl peptides, succinate, cardiolipin, cytochrome C...
With a more sensitive method of early neuroprognostication after cardiac arrest the limited medical resources could be used more effectively in patients with chance of good neurological recovery.
Aim of the study
The aim of this study is to research the role of mitochondrial damage-associated molecular patterns in patients after cardiac arrest.
- Determine normal plasma values of mitochondrial damage-associated molecular patterns in healthy population.
- Compare current prognostic procedures of post-resuscitation neurological damage with prognostic value of mitochondrial DNA and cytochrome C in plasma.
Expected results
Due to central role of mitochondria in hypoxic-ischemic tissue damage a greater mitochondrial damage (measured trough release of mitochondrial damage-associated molecular patterns) is expected to have direct correlation with extent of tissue damage (also neurological). Currently published data indicate that patients with higher plasma mitochondrial DNA levels after cardiac arrest have higher mortality. Correlation of mitochondrial damage-associated molecular patterns to extent of neurological damage in survivors of cardiac arrest was not researched yet.
Methods
- Measurement of measure mitochondrial damage-associated molecular patterns in healthy population (mitochondrial DNA and cytochrome C).
- Determination of releasing profile of mitochondrial DNA and cytochrome C in survivors of cardiac arrest and establishment of best sample collection time.
- Calculation of predictive value for survival of cardiac arrest with good neurological outcome for mitochondrial DNA and cytochrome C.
Mitochondrial damage-associated molecular patterns will be measured in samples of plasma. Mitochondrial DNA will be measured using PCR method. Cytochrome C will be measured using ELISA.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 14 years and older
- Sex
- All
- Age groups
- Child, Adult, Older adult
- Study population
- Unconscious patients after cardiac arrest treated with therapeutic hypothermia.
Key inclusion criteria (2 listed)
- unconscious after cardiac arrest
- therapeutic hypothermia
Key exclusion criteria (1 listed)
- expected survival less than 24h
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BiomarkerPlasma mitochondrial DNA, plasma Cytochrome C | Diagnostic test | – |
Primary outcome
Correlation of plasma mitochondrial DNA and cytochrome C with survival with good neurological outcome (CPC 1 and 2) at hospital discharge
Time frame: In hospital mortality, 30days
Relationship between plasma mitochondrial DNA and cytochrome C with neurological damage after cardiac arrest
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Dec 2023.
- Background: PubMed 24614515Greer DM, Rosenthal ES, Wu O. Neuroprognostication of hypoxic-ischaemic coma in the therapeutic hypothermia era. Nat Rev Neurol. 2014 Apr;10(4):190-203. doi: 10.1038/nrneurol.2014.36. Epub 2014 Mar 11.
- Background: PubMed 26385451Girotra S, Chan PS, Bradley SM. Post-resuscitation care following out-of-hospital and in-hospital cardiac arrest. Heart. 2015 Dec;101(24):1943-9. doi: 10.1136/heartjnl-2015-307450. Epub 2015 Sep 18.
- Background: PubMed 22490673Arnalich F, Codoceo R, Lopez-Collazo E, Montiel C. Circulating cell-free mitochondrial DNA: a better early prognostic marker in patients with out-of-hospital cardiac arrest. Resuscitation. 2012 Jul;83(7):e162-3. doi: 10.1016/j.resuscitation.2012.03.032. Epub 2012 Apr 7. No abstract available.
- Background: PubMed 25295826Rodrigues Filho EM, Ikuta N, Simon D, Regner AP. Prognostic value of circulating DNA levels in critically ill and trauma patients. Rev Bras Ter Intensiva. 2014 Jul-Sep;26(3):305-12. doi: 10.5935/0103-507x.20140043.
- Background: PubMed 26067258Nakahira K, Hisata S, Choi AM. The Roles of Mitochondrial Damage-Associated Molecular Patterns in Diseases. Antioxid Redox Signal. 2015 Dec 10;23(17):1329-50. doi: 10.1089/ars.2015.6407. Epub 2015 Aug 17.
- Individual participant dataSharing planned: No
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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.
Marko Noč, MD study chair
UMC Ljubljana
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, run by University Medical Centre Ljubljana at 1 site in Slovenia.
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 2 inclusion and 1 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: status not confirmed, as of the sponsor's last update on 6 Dec 2023. 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 Slovenia. 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?
Results are not available in the source record.
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?
Correlation of plasma mitochondrial DNA and cytochrome C with survival with good neurological outcome (CPC 1 and 2) at hospital discharge (time frame: In hospital mortality, 30days). 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 NCT03539497, which also lists 5 linked publications.
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 6 Dec 2023.