Immune Checkpoint Inhibitor Associated Cardiovascular Adverse Events in Patients With Cancer (ITHACA)

May 20, 2025 updated by: Hanneke W. M. van Laarhoven

Immune checkpoint inhibitors (ICI) have revolutionized cancer treatment and are now approved for various types of cancer. The most common side effects of ICI are immune-related adverse events which can affect any organ or system in the body. Recently, concerns have also risen about cardiovascular effects of ICI. Retrospective studies showed an 4-5 times increased risk of developing an arterial thromboembolic event.

The mechanisms driving the ICI-associated risks of arterial thromboembolic events such as myocardial infarction and stroke, are unclear. Since the risk of a thromboembolism appears to be increased already during the first months after initiation of ICI, immune-related hypercoagulability or (autoimmune) antiphospholipid antibodies may play a role, but data to support this are lacking. The longer-term risk of arterial thromboembolism may be predominantly driven by (accelerated) atherosclerosis, a chronic low-grade inflammatory disease of the larger arteries. Therefore, this study evaluates the effect of ICI on progression of coronary non-calcifid plaque volume by using computed tomography angiography (CCTA).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Observational

Enrollment (Estimated)

214

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Adult male or female subjects are eligible for study participation if they have a confirmed cancer diagnosis

Description

Inclusion Criteria:

  • Patients with confirmed diagnosis of the following tumor types, any stage: esophageal, gastric or junction cancer, colorectal cancer, non-small cell lung carcinoma, melanoma, renal cell carcinoma
  • Prior to start of new therapy (i.e. immune checkpoint inhibitor, chemotherapy or follow-up in case of esophageal cancer)
  • Age ≥ 50 years

Exclusion Criteria:

  • ICI therapy in previous 12 months
  • Suspected or confirmed viral, fungal, or bacterial infectious disease
  • Use of immunosuppressive therapy prior to ICI start
  • Estimated glomerular filtration rate (eGFR) <30 mL/min/1.73m2
  • Known allergy to iodinated contrast agents
  • Atrial fibrillation

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
ICI group
Patients that receive immune checkpoint inhibitors
Diagnostic test: Coronary computed tomography angiography (CCTA) at baseline
Detailed imaging of coronary arteries
Diagnostic test: Coronary computed tomography angiography (CCTA) after 1 year
Detailed imaging of coronary arteries
Non-ICI group
Patients with similar malignancies, who do not receive immune checkpoint inhibitors
Diagnostic test: Coronary computed tomography angiography (CCTA) at baseline
Detailed imaging of coronary arteries
Diagnostic test: Coronary computed tomography angiography (CCTA) after 1 year
Detailed imaging of coronary arteries

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Non-calcified coronary plaque volume (difference between baseline and follow-up CT)
Time Frame: 1 year
1 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Plaque characteristics (differences between baseline and follow-up)
Time Frame: 1 year
Difference in plaque characteristics (i.e. fat attenuation index)
1 year
Differences in plasma biomarkers (pro-inflammatory markers) between baseline and follow-up
Time Frame: 3 months, 1 year
Immune cell composition, T cell composition, IL-1b, IL-6, NLRP3, IL-17, TNF-a, IFN-y
3 months, 1 year
Incidence of Arterial thromboembolic event
Time Frame: 1 year, 5 years
Incidence of Arterial Thromboembolic events, defined as major cardiovascular events (MACE), including nonfatal ischemic stroke, nonfatal myocardial infarction and cardiovascular death
1 year, 5 years

Other Outcome Measures

Outcome Measure
Time Frame
Venous thromboembolism
Time Frame: 1 year, 5 years
1 year, 5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hanneke W. M. van Laarhoven

Collaborators

Amsterdam UMC

Investigators

  • Principal Investigator: H.W.M. van Laarhoven, Prof. Dr., secretariaat.oncologie@amsterdamumc.nl

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 25, 2023

Primary Completion (Estimated)

December 31, 2025

Study Completion (Estimated)

December 31, 2025

Study Registration Dates

First Submitted

July 18, 2024

First Submitted That Met QC Criteria

July 24, 2024

First Posted (Actual)

July 25, 2024

Study Record Updates

Last Update Posted (Actual)

May 22, 2025

Last Update Submitted That Met QC Criteria

May 20, 2025

Last Verified

May 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NL82446.018.22

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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