Cardiac SurgeryEPI-CARDNCT07389785
Age Related Chromatin Remodelling as a Therapeutic Target for Organ Protection in Cardiac Surgery
An observational study of Cardiac Surgery and Organ Protection, run by University of Leicester at 1 site in United Kingdom.
Trial summary
People who have multiple long-term conditions (MLTC) like kidney disease or lung disease are at higher risk of developing organ damage and poor quality of life following heart surgery. Decades of research have failed to identify drugs or treatments that prevent this. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cardiac Surgery, Organ Protection, Ageing
- What is being tested?
- other
- How many people
- 3,055 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 29 Sep 2025to 30 Jun 2030
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Adult cardiac surgery patients.
Who may be able to join
- Adult patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) enrolled in seven clinical studies in five UK centres.
Who cannot join
- Patients who did not consent to participate in the included trials, or participants who did not consent for secondary research of their data and samples.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
University of Leicester
Leicester, Leicester, LE1 7RH
About this study
People who have multiple long-term conditions (MLTC) like kidney disease or lung disease are at higher risk of developing organ damage and poor quality of life following heart surgery. Decades of research have failed to identify drugs or treatments that prevent this.
Our research has shown that people with MLTC have changes in their heart cells before surgery that are referred to by researchers as Biological Ageing. These changes combine to make people with MLTC more susceptible to organ damage after heart surgery, have delayed recovery, and lower quality of life.
Read more
This research programme will investigate the processes linking MLTC, changes in heart cells, and organ damage.
Our previous research suggests that MLTC lead to the infiltration of white cells from the blood into the heart muscle, a process called inflammageing. This alters the DNA in heart cells, reduces their pumping function and leaves them more likely to be damaged by surgery.
We have also shown that these changes are affected by obesity. We have also shown that changes in other types of heart cells with ageing are associated with damage to the lining of blood vessels, bleeding and damage to the kidneys.
We will use existing clinical data from previous studies and molecular data from heart cells obtained at surgery to better understand the molecular changes underlying our previous observations. This includes data from previous trials of drugs and dietary modification that aimed to modify the cellular DNA changes caused by inflammageing.
Using external data, we will check whether similar results are evident in other studies. We will then select the most likely processes underlying our observations and test whether these relationships are causal using genomic analysis and the UK Biobank data. Finally, we will use established analytical methods to identify potential drugs that may target these processes.
Positive results will provide a better understanding of the heart damage that is often seen in people with MLTC as well as new treatments for evaluation on further research.
Read the detailed description
Organ injury is common following cardiac surgery, where it contributes to excess mortality, delayed recovery, progression of LTC, poor quality of life, and increased use of healthcare resources.
People with MLTC demonstrate increased susceptibility to organ injury and its complications. Using a multi-omics approach we have shown that MLTC are associated with biological ageing in human myocardium. Using snRNAseq, we have shown that progression of MLTC are associated with acceleration of biological ageing, characterised by T cell exhaustion, dysregulated tissue resident macrophage activation, and increased susceptibility of cardiomyocytes to metabolic stress.
Genetic modification of these processes altered susceptibility to 90-day mortality following cardiac surgery in UK Biobank. Reversal of biological ageing mechanisms including mTOR activation, histone modification, disabled autophagy, or cell senescence reduces the susceptibility of myocardium to ischaemia reperfusion injury in mice. These observations lead us to hypothesise that pre-surgery reversal of biological ageing may have organ protective effects.
Cellular ageing is characterised by changes in chromatin accessibility that are determined by histone DNA interaction. The interaction between histones and DNA in the nucleosome determine the accessibility of promoters, enhancers, and transcription factors to molecular DNA and subsequently gene expression. Reversal of age-related changes in chromatin prevents cardiac ageing in mice.
In preliminary work we have shown that genetic modification underlying biological ageing in human myocardial biopsies is determined in part by changes in chromatin accessibility. We have shown associations between MLTC including obesity, genetic modification, and organ injury affecting the heart, kidney and vascular endothelium (bleeding). We now propose to comprehensively characterise the changes in chromatin accessibility, gene expression, cell secretomes and cell-cell interactions and single cell resolution that underly these observations.
This will be the first study to use integrated multi-omics to identify cellular phenotypes associated with different stages of biological ageing. The study will explore the contribution of a central hallmark of biological ageing; chromatin accessibility. Observational data from multi-omics snRNAseq and snATACseq will be validated in external datasets, and the causal effect of chromatin accessibility of susceptibility to organ injury will be explored using secondary analyses of RCTs. This research represents a first in man analysis of the role of chromatin remodelling in myocardial ageing and susceptibility to organ injury.
- Conditions
- Cardiac Surgery, Organ Protection, Ageing
- Being tested
- other
- Keywords
- chromatin, cardiac surgery, organ protection, multiple long-term conditions, ageing
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
otherOther
This is not an interventional study.
| Study group | Role | What they receive |
|---|---|---|
| MARACAS | Prospective, single-centre observational case-control study. Receives: Other: other | |
| REDWASH | A multicenter parallel-group randomized controlled trial. Receives: Other: other | |
| REVAKI-2 | Phase IIB placebo-controlled randomised clinical trial. Receives: Other: other | |
| OB-CARD | Prospective, single-centre case control study. Receives: Other: other | |
| COPTIC-2 | Retrospective, single-centre observational cohort trial. Receives: Other: other | |
| VAL-CARD | Single-centre, unblinded, randomised controlled trial (Phase 2b). Receives: Other: other | |
| PRE-OP ENERGY | Single-centre, unblinded, parallel group, randomised controlled trial. Receives: Other: other |
What is being measured
The primary outcome is the main question the study is designed to answer.
Study 1
For the clinical studies, outcomes will be restricted to those measured prospectively in the individual studies.
For the UK Biobank data, the primary outcome is time to death or emergency re-hospitalisation requiring overnight admission within 365 days following discharge after major surgery.
Measured: 5 years
Study 2
The analysis will identify differentially expressed genes, gene pathways, and networks in cell types by phenotype. The data will also identify differences in promoter accessibility by cell type and phenotype
Measured: 5 years
Study 3
These studies will provide quantitative targeted validation of genes, proteins and DNA accessibility by cell type and phenotype in human myocardial biopsies obtained at surgery in the listed studies.
We will identify anonymised publicly available external data sources that have evaluated biological ageing and inflammageing in human tissues. We will duplicate our primary genomics analysis in this secondary dataset.
Measured: 5 years
Study 4
We will quantify the effects of genetic modification of key genes and pathways identified in Studies 1-3 on mortality and freedom from hospitalisation in UK Biobank.
Measured: 5 years
Study 5
Clinical outcomes: Area under the troponin curve from baseline to 48 hours post-surgery.
Measured: 48 hours post-operation
Study 5
Clinical outcomes: Area under the creatinine curve from baseline to 72 hours post-surgery.
Measured: 72 hours post-operation
Study 5
Process outcomes: Valproate exposure
Measured: 6 weeks
Study 5
Process outcomes: Calorific intake
Measured: 6 weeks
Study 5
Process outcomes: Weight gain.
Measured: 6 weeks
Study 5
Experimental Outcomes: Combined snRNAseq/ ATACseq in myocardial biopsies (5 per group) obtained at surgery.
Measured: 1 day (operation day)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Feb 2026
- Study start29 Sep 2025
- Primary completion30 Jun 2030 (estimated)
- Study completion30 Jun 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cardiac SurgeryStudies of the same condition, open and under way.
- 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
- Retrospective
- Enrolment
- 3,055 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Leicester
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Gavin J Murphy, BSc, MBChB, FRCS, MD, FRCS CTh, Principal investigator, University of Leicester
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07389785
- Sponsor's protocol ID
- 1086
- Other IDs
- 356697
- Acronym
- EPI-CARD
- Status last verified
- Jan 2026
- First submitted
- 17 Sep 2025
- Last updated
- 5 Feb 2026
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 5 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Age Related Chromatin Remodelling as a Therapeutic Target for Organ Protection in Cardiac Surgery
- ClinicalTrials.gov ID
- NCT07389785
- Acronym / sponsor ID
- EPI-CARD / 1086
- Conditions
- Cardiac Surgery, Organ Protection, Ageing
- Keywords
- chromatin, cardiac surgery, organ protection, multiple long-term conditions, ageing
- Study type
- Observational
- Recruitment status
- Active, not recruiting
- Enrolment
- 3,055 participants (actual)
- Lead sponsor
- University of LeicesterUniversity, hospital or other
- Study start
- 29 Sep 2025 (actual)
- Primary completion
- 30 Jun 2030 (estimated)
- Study completion
- 30 Jun 2030 (estimated)
- First posted
- 5 Feb 2026 (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.
People who have multiple long-term conditions (MLTC) like kidney disease or lung disease are at higher risk of developing organ damage and poor quality of life following heart surgery. Decades of research have failed to identify drugs or treatments that prevent this.
Our research has shown that people with MLTC have changes in their heart cells before surgery that are referred to by researchers as Biological Ageing. These changes combine to make people with MLTC more susceptible to organ damage after heart surgery, have delayed recovery, and lower quality of life.
This research programme will investigate the processes linking MLTC, changes in heart cells, and organ damage.
Our previous research suggests that MLTC lead to the infiltration of white cells from the blood into the heart muscle, a process called inflammageing. This alters the DNA in heart cells, reduces their pumping function and leaves them more likely to be damaged by surgery.
We have also shown that these changes are affected by obesity. We have also shown that changes in other types of heart cells with ageing are associated with damage to the lining of blood vessels, bleeding and damage to the kidneys.
We will use existing clinical data from previous studies and molecular data from heart cells obtained at surgery to better understand the molecular changes underlying our previous observations. This includes data from previous trials of drugs and dietary modification that aimed to modify the cellular DNA changes caused by inflammageing.
Using external data, we will check whether similar results are evident in other studies. We will then select the most likely processes underlying our observations and test whether these relationships are causal using genomic analysis and the UK Biobank data. Finally, we will use established analytical methods to identify potential drugs that may target these processes.
Positive results will provide a better understanding of the heart damage that is often seen in people with MLTC as well as new treatments for evaluation on further research.
Detailed description
Organ injury is common following cardiac surgery, where it contributes to excess mortality, delayed recovery, progression of LTC, poor quality of life, and increased use of healthcare resources.
People with MLTC demonstrate increased susceptibility to organ injury and its complications. Using a multi-omics approach we have shown that MLTC are associated with biological ageing in human myocardium. Using snRNAseq, we have shown that progression of MLTC are associated with acceleration of biological ageing, characterised by T cell exhaustion, dysregulated tissue resident macrophage activation, and increased susceptibility of cardiomyocytes to metabolic stress.
Genetic modification of these processes altered susceptibility to 90-day mortality following cardiac surgery in UK Biobank. Reversal of biological ageing mechanisms including mTOR activation, histone modification, disabled autophagy, or cell senescence reduces the susceptibility of myocardium to ischaemia reperfusion injury in mice. These observations lead us to hypothesise that pre-surgery reversal of biological ageing may have organ protective effects.
Cellular ageing is characterised by changes in chromatin accessibility that are determined by histone DNA interaction. The interaction between histones and DNA in the nucleosome determine the accessibility of promoters, enhancers, and transcription factors to molecular DNA and subsequently gene expression. Reversal of age-related changes in chromatin prevents cardiac ageing in mice.
In preliminary work we have shown that genetic modification underlying biological ageing in human myocardial biopsies is determined in part by changes in chromatin accessibility. We have shown associations between MLTC including obesity, genetic modification, and organ injury affecting the heart, kidney and vascular endothelium (bleeding). We now propose to comprehensively characterise the changes in chromatin accessibility, gene expression, cell secretomes and cell-cell interactions and single cell resolution that underly these observations.
This will be the first study to use integrated multi-omics to identify cellular phenotypes associated with different stages of biological ageing. The study will explore the contribution of a central hallmark of biological ageing; chromatin accessibility. Observational data from multi-omics snRNAseq and snATACseq will be validated in external datasets, and the causal effect of chromatin accessibility of susceptibility to organ injury will be explored using secondary analyses of RCTs. This research represents a first in man analysis of the role of chromatin remodelling in myocardial ageing and susceptibility to organ injury.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 7
| Arm | Type | Receives |
|---|---|---|
| MARACAS | – | Other: otherProspective, single-centre observational case-control study. |
| REDWASH | – | Other: otherA multicenter parallel-group randomized controlled trial. |
| REVAKI-2 | – | Other: otherPhase IIB placebo-controlled randomised clinical trial. |
| OB-CARD | – | Other: otherProspective, single-centre case control study. |
| COPTIC-2 | – | Other: otherRetrospective, single-centre observational cohort trial. |
| VAL-CARD | – | Other: otherSingle-centre, unblinded, randomised controlled trial (Phase 2b). |
| PRE-OP ENERGY | – | Other: otherSingle-centre, unblinded, parallel group, randomised controlled trial. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Adult cardiac surgery patients.
Key inclusion criteria (1 listed)
- Adult patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) enrolled in seven clinical studies in five UK centres.
Key exclusion criteria (1 listed)
- Patients who did not consent to participate in the included trials, or participants who did not consent for secondary research of their data and samples.
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 |
|---|---|---|
| otherThis is not an interventional study. | Other | COPTIC-2, MARACAS, OB-CARD, PRE-OP ENERGY, REDWASH, REVAKI-2, VAL-CARD |
Primary outcome
Study 1
Time frame: 5 years
For the clinical studies, outcomes will be restricted to those measured prospectively in the individual studies. For the UK Biobank data, the primary outcome is time to death or emergency re-hospitalisation requiring overnight admission within 365 days following discharge after major surgery.
Study 2
Time frame: 5 years
The analysis will identify differentially expressed genes, gene pathways, and networks in cell types by phenotype. The data will also identify differences in promoter accessibility by cell type and phenotype
Study 3
Time frame: 5 years
These studies will provide quantitative targeted validation of genes, proteins and DNA accessibility by cell type and phenotype in human myocardial biopsies obtained at surgery in the listed studies. We will identify anonymised publicly available external data sources that have evaluated biological ageing and inflammageing in human tissues. We will duplicate our primary genomics analysis in this secondary dataset.
Study 4
Time frame: 5 years
We will quantify the effects of genetic modification of key genes and pathways identified in Studies 1-3 on mortality and freedom from hospitalisation in UK Biobank.
Study 5
Time frame: 48 hours post-operation
Clinical outcomes: Area under the troponin curve from baseline to 48 hours post-surgery.
Study 5
Time frame: 72 hours post-operation
Clinical outcomes: Area under the creatinine curve from baseline to 72 hours post-surgery.
Study 5
Time frame: 6 weeks
Process outcomes: Valproate exposure
Study 5
Time frame: 6 weeks
Process outcomes: Calorific intake
Study 5
Time frame: 6 weeks
Process outcomes: Weight gain.
Study 5
Time frame: 1 day (operation day)
Experimental Outcomes: Combined snRNAseq/ ATACseq in myocardial biopsies (5 per group) obtained at surgery.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Feb 2026.
- Individual participant dataSharing planned: Undecided
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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.
Gavin J Murphy, BSc, MBChB, FRCS, MD, FRCS CTh principal investigator
University of Leicester
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 Surgery and Organ Protection, run by University of Leicester at 1 site in United Kingdom.
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 1 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: under way, not looking for participants, as of the sponsor's last update on 5 Feb 2026. 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 United Kingdom. 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?
This study is still under way. Results are not available in the source record yet.
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?
Study 1 (time frame: 5 years). The study lists 10 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 5 Feb 2026.