Immune Checkpoint Inhibitor Associated Cardiovascular Adverse Events in Patients With Cancer (ITHACA)
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
Conditions
Study Type
Enrollment (Estimated)
Contacts and Locations
Study Contact
- Name: A Strijdhorst
- Phone Number: +31 205665975
- Email: a.strijdhorst@amsterdamumc.nl
Study Locations
-
-
Noord-Holland
-
Amsterdam, Noord-Holland, Netherlands, 1105AZ
- Recruiting
- Amsterdam UMC
-
Contact:
- A Strijdhorst
- Phone Number: +31 205665975
- Email: a.strijdhorst@amsterdamumc.nl
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Sampling Method
Study Population
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
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
|---|---|
|
ICI group
Patients that receive immune checkpoint inhibitors
|
Detailed imaging of coronary arteries
Detailed imaging of coronary arteries
|
|
Non-ICI group
Patients with similar malignancies, who do not receive immune checkpoint inhibitors
|
Detailed imaging of coronary arteries
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
Sponsor
Collaborators
Investigators
- Principal Investigator: H.W.M. van Laarhoven, Prof. Dr., secretariaat.oncologie@amsterdamumc.nl
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- NL82446.018.22
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
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