Cardiovascular DiseasesITHACANCT06519292
Immune Checkpoint Inhibitor Associated Cardiovascular Adverse Events in Patients With Cancer
An observational study of Cardiovascular Diseases and Arterial Thrombosis, run by Hanneke W. M. van Laarhoven at 1 site in Netherlands.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 50 years and older
- Conditions the study is for
- Cardiovascular Diseases, Arterial Thrombosis, Myocardial Infarction
- What is being tested?
- Coronary computed tomography angiography (CCTA) at baseline and Coronary computed tomography angiography (CCTA) after 1 year
- How many people
- 214 participants
- Where
- 1 siteNetherlands
- Study dates
- 25 Jan 2023to 31 Dec 2025
- 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 50 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Adult male or female subjects are eligible for study participation if they have a confirmed cancer diagnosis
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Netherlands1 site, 1 recruiting
- Recruiting
Amsterdam UMC
Amsterdam, North Holland, 1105AZ
A Strijdhorst, +31 205665975, a.strijdhorst@amsterdamumc.nl
About this study
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).
- Conditions
- Cardiovascular Diseases, Arterial Thrombosis, Myocardial Infarction, Stroke, Coronary Artery Disease, Atherosclerosis
- Being tested
- Coronary computed tomography angiography (CCTA) at baseline, Coronary computed tomography angiography (CCTA) after 1 year
- Keywords
- immune checkpoint inhibitors, cardiovascular disease, atherosclerosis
- Medical subject headings
- Cardiovascular Diseases, Myocardial Infarction, Stroke, Coronary Artery Disease, Atherosclerosis, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Coronary computed tomography angiography (CCTA) at baselineDiagnostic test
Detailed imaging of coronary arteries
Coronary computed tomography angiography (CCTA) after 1 yearDiagnostic test
Detailed imaging of coronary arteries
| Study group | Role | What they receive |
|---|---|---|
| ICI group | Patients that receive immune checkpoint inhibitors Receives: Diagnostic Test: Coronary computed tomography angiography (CCTA) at baseline; Diagnostic Test: Coronary computed tomography angiography (CCTA) after 1 year | |
| Non-ICI group | Patients with similar malignancies, who do not receive immune checkpoint inhibitors Receives: Diagnostic Test: Coronary computed tomography angiography (CCTA) at baseline; Diagnostic Test: Coronary computed tomography angiography (CCTA) after 1 year |
What is being measured
The primary outcome is the main question the study is designed to answer.
Non-calcified coronary plaque volume (difference between baseline and follow-up CT)
Measured: 1 year
Secondary outcomes (3)
Plaque characteristics (differences between baseline and follow-up)
Difference in plaque characteristics (i.e. fat attenuation index)
Measured: 1 year
Differences in plasma biomarkers (pro-inflammatory markers) between baseline and follow-up
Immune cell composition, T cell composition, IL-1b, IL-6, NLRP3, IL-17, TNF-a, IFN-y
Measured: 3 months, 1 year
Incidence of Arterial thromboembolic event
Incidence of Arterial Thromboembolic events, defined as major cardiovascular events (MACE), including nonfatal ischemic stroke, nonfatal myocardial infarction and cardiovascular death
Measured: 1 year, 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jul 2024
- Study start25 Jan 2023
- Primary completion31 Dec 2025 (estimated)
- Study completion31 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cardiovascular DiseasesStudies 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
- 214 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hanneke W. M. van Laarhoven
- Sponsor type
- University, hospital or other
- Collaborators
- Amsterdam UMC
- Responsible party
- Sponsor-investigator, Hanneke W. M. van Laarhoven, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
- Investigators
- H.W.M. van Laarhoven, Prof. Dr., Principal investigator, secretariaat.oncologie@amsterdamumc.nl
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06519292
- Sponsor's protocol ID
- NL82446.018.22
- Acronym
- ITHACA
- Status last verified
- May 2025
- First submitted
- 18 Jul 2024
- Last updated
- 22 May 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Immune Checkpoint Inhibitor Associated Cardiovascular Adverse Events in Patients With Cancer
- ClinicalTrials.gov ID
- NCT06519292
- Acronym / sponsor ID
- ITHACA / NL82446.018.22
- Conditions
- Cardiovascular Diseases, Arterial Thrombosis, Myocardial Infarction, Stroke, Coronary Artery Disease, Atherosclerosis
- Keywords
- immune checkpoint inhibitors, cardiovascular disease, atherosclerosis
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 214 participants (estimated)
- Lead sponsor
- Hanneke W. M. van LaarhovenUniversity, hospital or other
- Collaborators
- Amsterdam UMC
- Study start
- 25 Jan 2023 (actual)
- Primary completion
- 31 Dec 2025 (estimated)
- Study completion
- 31 Dec 2025 (estimated)
- First posted
- 25 Jul 2024 (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 (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 design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ICI group | – | Diagnostic Test: Coronary computed tomography angiography (CCTA) at baseline, Diagnostic Test: Coronary computed tomography angiography (CCTA) after 1 yearPatients that receive immune checkpoint inhibitors |
| Non-ICI group | – | Diagnostic Test: Coronary computed tomography angiography (CCTA) at baseline, Diagnostic Test: Coronary computed tomography angiography (CCTA) after 1 yearPatients with similar malignancies, who do not receive immune checkpoint inhibitors |
Who may qualify
- Ages
- 50 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Adult male or female subjects are eligible for study participation if they have a confirmed cancer diagnosis
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Coronary computed tomography angiography (CCTA) at baselineDetailed imaging of coronary arteries | Diagnostic test | ICI group, Non-ICI group |
| Coronary computed tomography angiography (CCTA) after 1 yearDetailed imaging of coronary arteries | Diagnostic test | ICI group, Non-ICI group |
Primary outcome
Non-calcified coronary plaque volume (difference between baseline and follow-up CT)
Time frame: 1 year
3 secondary outcomes
Plaque characteristics (differences between baseline and follow-up)
Time frame: 1 year
Differences in plasma biomarkers (pro-inflammatory markers) between baseline and follow-up
Time frame: 3 months, 1 year
Incidence of Arterial thromboembolic event
Time frame: 1 year, 5 years
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 22 May 2025.
- Individual participant dataSharing planned: No
Related trials for Cardiovascular Diseases
Active, not recruitingPhase 3
ENDOTHELION Study Group: Effect of Bosentan in NAION Patients
Ischemic Optic Neuropathy
Active, not recruiting
Digital Reinforcement of Motivational Interviewing Micro-Skills Among Primary Care Healthcare Professionals
Hypertension (Without Type 2 Diabetes Mellitus)
Not yet recruitingPhase 2
Study of YKST02 in Adults With Relapsed or Refractory Multiple Myeloma
Relapsed or Refractory Multiple Myeloma (RRMM)
RecruitingPhase 2
Engaging T-cells to Eliminate MRD in Newly Diagnosed Myeloma Optimizing Response With Talquetmab and Teclistamab (ROTATE)
Multiple Myeloma
Recruiting
PAW-Hydrogel for Chronic Wound Healing
Diabetic Foot Ulcer (DFU), Pressure Ulcer (PU)
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.
H.W.M. van Laarhoven, Prof. Dr. principal investigator
secretariaat.oncologie@amsterdamumc.nl
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 Cardiovascular Diseases and Arterial Thrombosis, run by Hanneke W. M. van Laarhoven at 1 site in Netherlands.
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 3 inclusion and 6 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: looking for participants now, as of the sponsor's last update on 22 May 2025. 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 Netherlands. 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 A Strijdhorst (+31 205665975, a.strijdhorst@amsterdamumc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Non-calcified coronary plaque volume (difference between baseline and follow-up CT) (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 22 May 2025.