CardiotoxicityPRIME-ICINCT07864727
Cardiac Biomarkers in Patients Receiving Immune Checkpoint Inhibitors (PRIME-ICI)
An observational study of Cardiotoxicity and Cardiac Biomarkers, run by South Tees Hospitals NHS Foundation Trust at 1 site in United Kingdom.
Trial summary
Immune checkpoint inhibitors (ICIs) are widely used cancer treatments. Blood tests such as cardiac troponin and N-terminal pro-B-type natriuretic peptide (NT-proBNP) can help clinicians investigate possible heart injury, but these markers may also be raised for other reasons such as infection, kidney dysfunction… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cardiotoxicity, Cardiac Biomarkers, Cancer
- How many people
- 300 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 12 Oct 2026to 31 Mar 2028
- 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: Adults with cancer treated at The James Cook University Hospital who are planned to start an immune checkpoint inhibitor-containing regimen and are enrolled at, or immediately prior to, ICI initiation. Patients already established on ICI therapy are not recruited.
Who may be able to join
- Adults aged 18 years or older.
- Planned to start any immune checkpoint inhibitor-containing treatment (PD-1, PD-L1, CTLA-4 or combination therapy).
- Enrolled at, or immediately prior to, ICI initiation, with residual blood available from routine clinical sampling where feasible.
- Provision of informed consent.
Who cannot join
- Recent acute coronary syndrome within 1 month prior to enrolment.
- Dialysis-dependent renal failure (patients with non-dialysis chronic kidney disease may be included and eGFR recorded).
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United Kingdom1 site
Academic Cardiovascular Unit, James Cook University Hospital
Middlesbrough, TS4 3BW
Saif Memon, MBBS, +44 (0)1642 850 850, saif.memon@nhs.net
About this study
Official title: Prospective Study of Cardiac Biomarker Elevation in Patients Receiving Immune Checkpoint Inhibitors
Immune checkpoint inhibitors (ICIs) are widely used cancer treatments. Blood tests such as cardiac troponin and N-terminal pro-B-type natriuretic peptide (NT-proBNP) can help clinicians investigate possible heart injury, but these markers may also be raised for other reasons such as infection, kidney dysfunction, arrhythmia, pulmonary embolism or fluid overload. PRIME-ICI is a prospective observational study of adults starting ICI therapy at The James Cook University Hospital. The study will mainly use leftover blood from routine clinical samples and routine electronic health-record data. Samples will be batch tested for NT-proBNP, high-sensitivity troponin I and T, and selected exploratory biomarkers. The study will determine how often cardiac biomarkers are elevated, describe the clinical circumstances in which elevations occur, and classify biomarker-positive episodes according to their most likely clinical phenotype. Participation does not alter cancer treatment, and research biomarker results are not used for real-time clinical decisions.
Read the detailed description
PRIME-ICI is a single-centre prospective observational cohort study enrolling adults at, or immediately prior to, the start of an immune checkpoint inhibitor-containing treatment regimen. Patients already established on ICI therapy are not recruited, in order to reduce survivorship and selection bias. Participants are followed through review of the electronic patient record for a minimum of 6 months.
The study primarily uses residual blood remaining after routine clinical testing. Residual samples obtained before ICI initiation, at available routine ICI/SACT treatment visits, and during acute hospital admissions or emergency-department observation episodes are identified where feasible and stored for later batch analysis. If no suitable residual baseline sample remains, one additional small baseline research blood sample may be taken at the first ICI treatment visit in accordance with the approved consent process.
The primary cardiac biomarkers are NT-proBNP, high-sensitivity cardiac troponin T (hs-cTnT), and high-sensitivity cardiac troponin I (hs-cTnI). Exploratory biomarkers include creatine kinase, alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase where sufficient sample is available and testing is analytically feasible. Contemporaneous routine clinical laboratory and clinical data are also collected where available.
Biomarker-positive episodes are described according to prespecified biomarker patterns and undergo structured clinical review using available routine clinical data. Adjudicated phenotypes include ICI-associated myocarditis, heart failure/congestion, acute coronary syndrome or ischaemic myocardial injury, other cardiovascular illness, non-cardiovascular/systemic illness, and indeterminate/not assessable. Where sufficient information is available, episodes are evaluated against ESC/IC-OS criteria for ICI-associated myocarditis and locally implemented UKONS thresholds. The study is designed to characterise background biomarker elevation and its clinical context; it is not powered to determine myocarditis incidence or diagnostic sensitivity/specificity.
- Conditions
- Cardiotoxicity, Cardiac Biomarkers, Cancer
- Keywords
- immune checkpoint inhibitor, cardio-oncology, cardiac troponin, ICI myocarditis
- Medical subject headings
- Cardiotoxicity, Neoplasms
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 |
|---|---|---|
| Adults initiating immune checkpoint inhibitor therapy | Adults aged 18 years or older enrolled at, or immediately prior to, initiation of any ICI-containing treatment regimen at The James Cook University Hospital. Participants receive cancer treatment according to routine clinical care; the study does not assign treatment. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with cardiac biomarker elevation across evaluable biomarker episodes
Proportion of evaluable routine-treatment and acute admission/ED observation biomarker episodes in which NT-proBNP, hs-cTnI and/or hs-cTnT is above the applicable local laboratory upper limit of normal. Estimates will be reported with 95% confidence intervals.
Measured: From baseline/ICI initiation through a minimum of 6 months follow-up
Adjudicated clinical phenotype of biomarker-positive episodes
Distribution of biomarker-positive episodes across prespecified adjudicated phenotypes: ICI-associated myocarditis; heart failure/congestion; acute coronary syndrome/ischaemic myocardial injury; other cardiovascular illness; non-cardiovascular/systemic illness; and indeterminate/not assessable.
Measured: From baseline/ICI initiation through a minimum of 6 months follow-up
Secondary outcomes (4)
Distribution of prespecified biomarker patterns
Number and proportion of biomarker-positive episodes classified as isolated NT-proBNP elevation, isolated troponin elevation, combined NT-proBNP/troponin elevation, or cardiac biomarker elevation accompanied by systemic/immune-toxicity biomarker abnormalities.
Measured: From baseline/ICI initiation through a minimum of 6 months follow-up
Classification against ICI-myocarditis diagnostic frameworks
Among biomarker-positive episodes with sufficient contemporaneous data, number/proportion meeting ESC/IC-OS criteria for ICI-associated myocarditis and description against locally implemented UKONS diagnostic/escalation thresholds. Episodes lacking sufficient data will be reported as not assessable.
Measured: From baseline/ICI initiation through a minimum of 6 months follow-up
Exploratory systemic biomarker abnormalities associated with cardiac biomarker elevation
Prevalence and magnitude of CK, ALT, AST and LDH abnormalities, together with available routine inflammatory, haematological and renal markers, in relation to cardiac biomarker elevation and adjudicated clinical phenotype.
Measured: From baseline/ICI initiation through a minimum of 6 months follow-up
Trajectory of cardiac biomarker abnormalities
Among episodes with biomarker elevation, subsequent available values will be used to describe whether levels normalise, improve, persist or worsen, and where possible the trajectory will be described in relation to clinical context, cardiovascular therapy, immunosuppression, ICI interruption and admission diagnosis.
Measured: From baseline/ICI initiation through a minimum of 6 months follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Oct 2026
- Study start12 Oct 2026 (estimated)
- Primary completion31 Mar 2028 (estimated)
- Study completion31 Mar 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for CardiotoxicityStudies 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
- Prospective
- Enrolment
- 300 participants (estimated)
Sponsor and investigators
- Lead sponsor
- South Tees Hospitals NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- David Austin, MD, Principal investigator, South Tees Hospitals NHS Foundation Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07864727
- Sponsor's protocol ID
- 26/004
- Acronym
- PRIME-ICI
- Status last verified
- Oct 2026
- First submitted
- 2 Oct 2026
- Last updated
- 8 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: No external individual participant-level dataset is currently planned for public sharing; aggregate results will be disseminated.
Publications
Mahmood SS, Fradley MG, Cohen JV, Nohria A, Reynolds KL, Heinzerling LM, Sullivan RJ, Damrongwatanasuk R, Chen CL, Gupta D, Kirchberger MC, Awadalla M, Hassan MZO, Moslehi JJ, Shah SP, Ganatra S, Thavendiranathan P, Lawrence DP, Groarke JD, Neilan TG. Myocarditis in Patients Treated With Immune Checkpoint Inhibitors. J Am Coll Cardiol. 2018 Apr 24;71(16):1755-1764. doi: 10.1016/j.jacc.2018.02.037. Epub 2018 Mar 19.
PubMed 29567210van den Berg PF, Bracun V, Noordman M, van der Meer P, Shi C, Oosting SF, Aboumsallem JP, de Wit S, Meijers WC, Jalving M, van Kruchten M, de Boer RA. Elevations of Cardiac Troponin in Patients Receiving Immune Checkpoint Inhibitors: Data From a Prospective Study. JACC Adv. 2024 Nov 7;3(12):101375. doi: 10.1016/j.jacadv.2024.101375. eCollection 2024 Dec.
PubMed 39583866Pudil R, Mueller C, Celutkiene J, Henriksen PA, Lenihan D, Dent S, Barac A, Stanway S, Moslehi J, Suter TM, Ky B, Sterba M, Cardinale D, Cohen-Solal A, Tocchetti CG, Farmakis D, Bergler-Klein J, Anker MS, Von Haehling S, Belenkov Y, Iakobishvili Z, Maack C, Ciardiello F, Ruschitzka F, Coats AJS, Seferovic P, Lainscak M, Piepoli MF, Chioncel O, Bax J, Hulot JS, Skouri H, Hagler-Laube ES, Asteggiano R, Fernandez TL, de Boer RA, Lyon AR. Role of serum biomarkers in cancer patients receiving cardiotoxic cancer therapies: a position statement from the Cardio-Oncology Study Group of the Heart Failure Association and the Cardio-Oncology Council of the European Society of Cardiology. Eur J Heart Fail. 2020 Nov;22(11):1966-1983. doi: 10.1002/ejhf.2017. Epub 2020 Oct 20.
PubMed 33006257
Study at a glance
From the registry record, last updated by the sponsor on 8 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective Study of Cardiac Biomarker Elevation in Patients Receiving Immune Checkpoint Inhibitors
- ClinicalTrials.gov ID
- NCT07864727
- Acronym / sponsor ID
- PRIME-ICI / 26/004
- Conditions
- Cardiotoxicity, Cardiac Biomarkers, Cancer
- Keywords
- immune checkpoint inhibitor, cardio-oncology, cardiac troponin, ICI myocarditis
- Study type
- Observational
- Recruitment status
- Not yet recruiting
- Enrolment
- 300 participants (estimated)
- Lead sponsor
- South Tees Hospitals NHS Foundation TrustUniversity, hospital or other
- Study start
- 12 Oct 2026 (estimated)
- Primary completion
- 31 Mar 2028 (estimated)
- Study completion
- 31 Mar 2028 (estimated)
- First posted
- 8 Oct 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.
Immune checkpoint inhibitors (ICIs) are widely used cancer treatments. Blood tests such as cardiac troponin and N-terminal pro-B-type natriuretic peptide (NT-proBNP) can help clinicians investigate possible heart injury, but these markers may also be raised for other reasons such as infection, kidney dysfunction, arrhythmia, pulmonary embolism or fluid overload. PRIME-ICI is a prospective observational study of adults starting ICI therapy at The James Cook University Hospital. The study will mainly use leftover blood from routine clinical samples and routine electronic health-record data. Samples will be batch tested for NT-proBNP, high-sensitivity troponin I and T, and selected exploratory biomarkers. The study will determine how often cardiac biomarkers are elevated, describe the clinical circumstances in which elevations occur, and classify biomarker-positive episodes according to their most likely clinical phenotype. Participation does not alter cancer treatment, and research biomarker results are not used for real-time clinical decisions.
Detailed description
PRIME-ICI is a single-centre prospective observational cohort study enrolling adults at, or immediately prior to, the start of an immune checkpoint inhibitor-containing treatment regimen. Patients already established on ICI therapy are not recruited, in order to reduce survivorship and selection bias. Participants are followed through review of the electronic patient record for a minimum of 6 months.
The study primarily uses residual blood remaining after routine clinical testing. Residual samples obtained before ICI initiation, at available routine ICI/SACT treatment visits, and during acute hospital admissions or emergency-department observation episodes are identified where feasible and stored for later batch analysis. If no suitable residual baseline sample remains, one additional small baseline research blood sample may be taken at the first ICI treatment visit in accordance with the approved consent process.
The primary cardiac biomarkers are NT-proBNP, high-sensitivity cardiac troponin T (hs-cTnT), and high-sensitivity cardiac troponin I (hs-cTnI). Exploratory biomarkers include creatine kinase, alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase where sufficient sample is available and testing is analytically feasible. Contemporaneous routine clinical laboratory and clinical data are also collected where available.
Biomarker-positive episodes are described according to prespecified biomarker patterns and undergo structured clinical review using available routine clinical data. Adjudicated phenotypes include ICI-associated myocarditis, heart failure/congestion, acute coronary syndrome or ischaemic myocardial injury, other cardiovascular illness, non-cardiovascular/systemic illness, and indeterminate/not assessable. Where sufficient information is available, episodes are evaluated against ESC/IC-OS criteria for ICI-associated myocarditis and locally implemented UKONS thresholds. The study is designed to characterise background biomarker elevation and its clinical context; it is not powered to determine myocarditis incidence or diagnostic sensitivity/specificity.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Adults initiating immune checkpoint inhibitor therapy | – | –Adults aged 18 years or older enrolled at, or immediately prior to, initiation of any ICI-containing treatment regimen at The James Cook University Hospital. Participants receive cancer treatment according to routine clinical care; the study does not assign treatment. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Adults with cancer treated at The James Cook University Hospital who are planned to start an immune checkpoint inhibitor-containing regimen and are enrolled at, or immediately prior to, ICI initiation. Patients already established on ICI therapy are not recruited.
Key inclusion criteria (4 listed)
- Adults aged 18 years or older.
- Planned to start any immune checkpoint inhibitor-containing treatment (PD-1, PD-L1, CTLA-4 or combination therapy).
- Enrolled at, or immediately prior to, ICI initiation, with residual blood available from routine clinical sampling where feasible.
- Provision of informed consent.
Key exclusion criteria (2 listed)
- Recent acute coronary syndrome within 1 month prior to enrolment.
- Dialysis-dependent renal failure (patients with non-dialysis chronic kidney disease may be included and eGFR recorded).
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
Number of participants with cardiac biomarker elevation across evaluable biomarker episodes
Time frame: From baseline/ICI initiation through a minimum of 6 months follow-up
Proportion of evaluable routine-treatment and acute admission/ED observation biomarker episodes in which NT-proBNP, hs-cTnI and/or hs-cTnT is above the applicable local laboratory upper limit of normal. Estimates will be reported with 95% confidence intervals.
Adjudicated clinical phenotype of biomarker-positive episodes
Time frame: From baseline/ICI initiation through a minimum of 6 months follow-up
Distribution of biomarker-positive episodes across prespecified adjudicated phenotypes: ICI-associated myocarditis; heart failure/congestion; acute coronary syndrome/ischaemic myocardial injury; other cardiovascular illness; non-cardiovascular/systemic illness; and indeterminate/not assessable.
4 secondary outcomes
Distribution of prespecified biomarker patterns
Time frame: From baseline/ICI initiation through a minimum of 6 months follow-up
Classification against ICI-myocarditis diagnostic frameworks
Time frame: From baseline/ICI initiation through a minimum of 6 months follow-up
Exploratory systemic biomarker abnormalities associated with cardiac biomarker elevation
Time frame: From baseline/ICI initiation through a minimum of 6 months follow-up
Trajectory of cardiac biomarker abnormalities
Time frame: From baseline/ICI initiation through a minimum of 6 months follow-up
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 8 Oct 2026.
- Background: PubMed 29567210Mahmood SS, Fradley MG, Cohen JV, Nohria A, Reynolds KL, Heinzerling LM, Sullivan RJ, Damrongwatanasuk R, Chen CL, Gupta D, Kirchberger MC, Awadalla M, Hassan MZO, Moslehi JJ, Shah SP, Ganatra S, Thavendiranathan P, Lawrence DP, Groarke JD, Neilan TG. Myocarditis in Patients Treated With Immune Checkpoint Inhibitors. J Am Coll Cardiol. 2018 Apr 24;71(16):1755-1764. doi: 10.1016/j.jacc.2018.02.037. Epub 2018 Mar 19.
- Background: PubMed 39583866van den Berg PF, Bracun V, Noordman M, van der Meer P, Shi C, Oosting SF, Aboumsallem JP, de Wit S, Meijers WC, Jalving M, van Kruchten M, de Boer RA. Elevations of Cardiac Troponin in Patients Receiving Immune Checkpoint Inhibitors: Data From a Prospective Study. JACC Adv. 2024 Nov 7;3(12):101375. doi: 10.1016/j.jacadv.2024.101375. eCollection 2024 Dec.
- Background: PubMed 33006257Pudil R, Mueller C, Celutkiene J, Henriksen PA, Lenihan D, Dent S, Barac A, Stanway S, Moslehi J, Suter TM, Ky B, Sterba M, Cardinale D, Cohen-Solal A, Tocchetti CG, Farmakis D, Bergler-Klein J, Anker MS, Von Haehling S, Belenkov Y, Iakobishvili Z, Maack C, Ciardiello F, Ruschitzka F, Coats AJS, Seferovic P, Lainscak M, Piepoli MF, Chioncel O, Bax J, Hulot JS, Skouri H, Hagler-Laube ES, Asteggiano R, Fernandez TL, de Boer RA, Lyon AR. Role of serum biomarkers in cancer patients receiving cardiotoxic cancer therapies: a position statement from the Cardio-Oncology Study Group of the Heart Failure Association and the Cardio-Oncology Council of the European Society of Cardiology. Eur J Heart Fail. 2020 Nov;22(11):1966-1983. doi: 10.1002/ejhf.2017. Epub 2020 Oct 20.
- Individual participant dataSharing planned: No. No external individual participant-level dataset is currently planned for public sharing; aggregate results will be disseminated.
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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.
David Austin, MD principal investigator
South Tees Hospitals NHS Foundation Trust
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 Cardiotoxicity and Cardiac Biomarkers, run by South Tees Hospitals NHS Foundation Trust 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 4 inclusion and 2 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: opening soon, as of the sponsor's last update on 8 Oct 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?
Contact Saif Memon, MBBS (+44 (0)1642 850 850, saif.memon@nhs.net), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants with cardiac biomarker elevation across evaluable biomarker episodes (time frame: From baseline/ICI initiation through a minimum of 6 months follow-up). The study lists 2 primary outcomes in all. 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 NCT07864727, which also lists 3 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 8 Oct 2026.