Evaluating the accuracy of organ injury biomarkers to personalise protection interventions in adult cardiac surgery
| ISRCTN | ISRCTN20630689 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN20630689 |
| IRAS number | 293173 |
| Secondary identifying numbers | CPMS 48955, IRAS 293173 |
- Submission date
- 26/07/2021
- Registration date
- 03/09/2021
- Last edited
- 23/04/2025
- Recruitment status
- No longer recruiting
- Overall study status
- Ongoing
- Condition category
- Circulatory System
Plain English summary of protocol
Background and study aims
Organ injury and problems with the kidneys, heart and lungs are not uncommon after heart surgery and caring for patients who develop these issues takes a lot of resources. Progress towards preventing these problems is difficult because we don't fully understand the reasons why they happen. Cardiopulmonary bypass (CPB) during surgery is thought to be a cause, along with how generally healthy the patient is going into the surgery, but this is difficult to predict as there are lots of health problems that people can have. It is thought that these different kinds of health problems are what is behind the differences in how people are affected by organ injury as a result of their heart operation. These may also be the reason why treatments to prevent organ injury have a different effect in animal studies compared to humans. By learning more about these different health problems, patients may be grouped more accurately and we could develop ways to prevent organ injury in a more personal way. The aim of this study is to investigate how accurately organ injury can be predicted in patients having a heart operation using measurements within the body called biomarkers along with clinical research data about their health.
Who can participate?
Adult patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) enrolled in the COPTIC trial (ISRCTN20778544) in Bristol UK for whom there are available samples and data
What does the study involve?
Laboratory and computer analyses are carried out on stored samples from patients undergoing cardiac surgery with cardiopulmonary bypass.
What are the possible benefits and risks of participating?
Not applicable as the researchers are using stored samples and data.
Where is the study run from?
University of Leicester (UK)
When is the study starting and how long is it expected to run for?
October 2020 to April 2028
Who is funding the study?
British Heart Foundation (UK)
Who is the main contact?
Hardeep Aujla
ha200@le.ac.uk
Contact information
Scientific
Research Manager
Dept. Cardiovascular Sciences
University of Leicester
Leicester
LE3 9QP
United Kingdom
 ORCID ID |
0000-0002-5823-848X |
|---|---|
| Phone | +44 (0)116 250 2427 |
| ha200@le.ac.uk |
Study information
| Study design | Observational; Design type: Clinical Laboratory Study |
|---|---|
| Primary study design | Observational |
| Secondary study design | Clinical laboratory study |
| Study setting(s) | Hospital |
| Study type | Diagnostic |
| Participant information sheet | No participant information sheet available |
| Scientific title | Evaluating the diagnostic accuracy of novel organ injury biomarkers in adult cardiac surgery |
| Study acronym | COPTIC-2 |
| Study objectives | The overarching hypothesis is that existing clinical and biochemical definitions of post-cardiac surgery organ injury and dysfunction represent multiple molecular phenotypes. Identification of these different phenotypes will lead to new and effective prevention strategies and treatments. |
| Ethics approval(s) | Approved 29/03/2021, South Central - Berkshire REC (Bristol REC Centre, Whitefriars Level 3 Block B, Lewins Mead, Bristol, BS1 2NT, UK; +44 (0)207 104 8224, +44 (0)207 104 8270; berkshire.rec@hra.nhs.uk), REC ref: 21/SC/0118 |
| Health condition(s) or problem(s) studied | Cardiac surgery with cardiopulmonary bypass |
| Intervention | The researchers will see how accurately they can use measurements in the body (biomarkers) to predict organ injury. These biomarkers have been identified before in an ethically approved study (COPTIC). They will carry this out in stored samples of 2463 patients from this previous study. They have information on them already, including their baseline status. Only patients who consented for their samples and data to be used in future ethically approved studies will be used. The original study investigators in Bristol will undertake a consent audit to ensure this. The researchers will check to see if there are enough samples, and if the data is complete enough before including them in this study. They will then conduct laboratory and computer analyses to explore the study aims. |
| Intervention type | Procedure/Surgery |
| Primary outcome measure | Derived from data and samples collected pre- and post-surgery: 1. Novel biomarkers identified in existing studies including: 1.1. Serum cytokines considered to be indicators of the severity of the inflammatory response to surgery, measured from serum on the Luminex MAGPIX Analyser (Oosterhout, NL) 1.2. Extracellular vesicles in plasma (EV) assessed by flow cytometry 1.3. Exosome and EV derived microRNA assessed by quantitative reverse transcription PCR (qRT-PCR) and next-generation sequencing 1.4. Targeted metabolomics for biomarkers of frailty, acute kidney injury acute lung injury, and coagulopathy, analysed using a targeted assay on a Thermo Qunativa interfaced with a Vanquish LC25 1.5. Other organ injury biomarkers; plasma proteins, coagulation assays, performed by next-generation sequencing and analysis of a panel of metabolites by mass spectrometry 2. Acute kidney injury (AKI) defined by clinical consensus criteria: RIFLE, AKIN, KDIGO, or by serial biomarker levels: serum creatinine, and soluble urokinase plasminogen activator receptor (uPAR) 3. Myocardial injury defined clinically as low cardiac output, which is new intra- or postoperative intra-aortic balloon pump insertion or a cardiac index of <2.2 l min-1 m-2 refractory to appropriate intravascular volume expansion after correction or attempted correction of any dysrhythmias, or the administration of ionotropes including dobutamine, enoximone, milrinone, levosimendan and adrenaline, or by serial biomarker levels: serum troponin 4. Acute lung injury (ALI) defined by clinical consensus criteria: ALI Score, Berlin ARDS Score, or by serial PaO₂/FiO₂ ratio 5. Coagulopathy defined using the COPTIC trial definition, or by point-of-care or laboratory tests of coagulopathy |
| Secondary outcome measures | Extracted from anonymised clinical trial data pre- and post-surgery: 1. Any red cell transfusion* 2. Red cell transfusion of ≥5 units* 3. Mortality 4. Myocardial infarction 5. Intra-aortic balloon pump 6. Stroke 7. Acute kidney injury (Yes/No) 8. Serum creatinine to estimate AKI grade 1, AKI grade 2, and AKI grade 3 on days 1-5 post surgery 9. Sepsis 10. Length of stay in ICU 11. Length of stay in hospital *reoperation of red cell transfusion for surgical causes of bleeding are excluded |
| Overall study start date | 01/10/2020 |
| Completion date | 01/04/2028 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Sex | Both |
| Target number of participants | Planned Sample Size: 2463; UK Sample Size: 2463 |
| Total final enrolment | 2437 |
| Key inclusion criteria | Adult patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) enrolled in the COPTIC trial (ISRCTN20778544) in Bristol UK for whom there are available samples and data |
| Key exclusion criteria | Participants of the COPTIC trial who did not provide consent for the use of samples and/or data for further ethically approved research (i.e., the present trial), and for whom there are insufficient samples and data |
| Date of first enrolment | 01/09/2021 |
| Date of final enrolment | 01/09/2023 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
University of Leicester
Department of Cardiovascular Sciences
Clinical Sciences Wing
Glenfield Hospital
Leicester
LE3 9QP
United Kingdom
Sponsor information
University/education
c/o Cat Taylor
Research Governance Office
Academic Dept.
Leicester General Hospital
Leicester
LE5 4PW
England
United Kingdom
| Phone | +44 (0)1162584867 |
|---|---|
| rgosponsor@le.ac.uk | |
| Website | http://www.le.ac.uk/ |
"ROR" |
https://ror.org/04h699437 |
Funders
Funder type
Charity
Private sector organisation / Trusts, charities, foundations (both public and private)
- Alternative name(s)
- the_bhf, The British Heart Foundation, BHF
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 01/04/2026 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| Publication and dissemination plan | 1. The researchers plan to publish the protocol 2. Planned publication in a high-impact peer-reviewed journal |
| IPD sharing plan | The data-sharing plans for the current study are unknown and will be made available at a later date |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| HRA research summary | 28/06/2023 | No | No | ||
| Preprint results | 17/10/2024 | 23/04/2025 | No | No |
Editorial Notes
23/04/2025: Preprint and total final enrolment added. The overall study end date was changed from 01/04/2025 to 01/04/2028.
12/09/2024: The following changes were made to the trial record:
1. The overall study end date was changed from 01/09/2023 to 01/04/2025.
2. The intention to publish date was changed from 01/09/2024 to 01/04/2026.
3. The plain English summary was updated to reflect these changes.
26/07/2021: Trial's existence confirmed by the NIHR.
