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
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