CancerCAVACINCT05699915
Extensive CArdioVAscular Characterization and Follow-up of Patients Receiving Immune Checkpoint Inhibitors
A study testing Cardiology consultation, Chest Computed Tomography (CT) without contrast and Non-invasive endothelial function tests in people with Cancer and Immune-related Adverse Event, run by Algemeen Ziekenhuis Maria Middelares at 4 sites in Belgium.
Trial summary
The goal of this prospective, multicentre study is to investigate short- and long-term cardiovascular effects in cancer patients treated with immune checkpoint inhibitors (ICIs). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cancer, Immune-related Adverse Event, Cardiac Abnormalities, Variable
- What is being tested?
- Cardiology consultation, Chest Computed Tomography (CT) without contrast and Non-invasive endothelial function tests
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 105 participants
- Where
- 4 sitesBelgium
- Study dates
- 7 Jan 2022to 12 Jul 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
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
Who may be able to join
- Have a solid tumour and will receive one of the following therapies based on current evidence based clinical guidelines: anti-programmed cell death protein-1 (PD-1), anti-programmed cell death ligand-1 (PD-L1) and/or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) therapy
- Be literate in Dutch or English
Who cannot join
- Prior treatment with immunotherapy (immune checkpoint inhibitors, T-cell transfer therapy, cancer treatment vaccines or immune system modulators).
- Patients who will receive ICIs in combination with an additional systemic anti-cancer regimen (chemotherapy, tyrosine kinase inhibitors,…).
- Having a known history of human immunodeficiency virus (HIV) infection.
- Having a known history of hepatitis B (defined as hepatitis B surface antigen [HBsAg] reactive) or known active hepatitis C virus (defined as detectable RNA via qualitative nucleic acid testing) infection.
- Having a diagnosis of immunodeficiency or is receiving chronic/active systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent)
Trial locations and contacts
4 sites in 1 country.
Belgium4 sites
Antwerp University Hospital
Antwerp, Antwerp, 2650
AZ Sint-Vincentius Deinze
Deinze, East-Flanders, 9800
Algemeen Ziekenhuis Maria Middelares
Ghent, East-Flanders, 9000
AZ Sint-Elisabeth Zottegem
Zottegem, East-Flanders, 9620
About this study
Official title: Extensive CArdioVAscular Characterization and Follow-up of Patients Receiving Immune Checkpoint Inhibitors: a Prospective Multicentre Study
The goal of this prospective, multicentre study is to investigate short- and long-term cardiovascular effects in cancer patients treated with immune checkpoint inhibitors (ICIs).
The main question[s] it aims to answer are:
Read more
- To investigate troponin and NT-proBNP values in patients receiving ICIs and their association with ICI-induced CV abnormalities and MACEs.
- Study the calcium score, systolic, and diastolic (dys)function.
- Evaluate associations between patient/disease characteristics / transthoracic echocardiography parameters / electrocardiography parameters and troponin / NT-proBNP levels.
Participants will be closely monitored by performing the following additional visits and testing:
- Chest CT scan prior to treatment start, after 12 and 24 months.
- Consultation with a cardiologist at baseline, 3, 6, 12 and 24 months, who will perform an electrocardiogram and echocardiogram.
- One additional blood sample prior to treatment start, after 3, 6, 12 and 24 months. An extra blood sample could be taken in case of sudden heart problems.
- Non-invasive endothelial function tests prior to treatment start, after 12 and 24 months.
Read the detailed description
The increasing use of immune checkpoint inhibitors (ICIs) in the treatment of both advanced and early stages of various malignancies has resulted in a substantial increase in the incidence of cardiovascular immune related adverse events (irAEs). The current guidelines are based on anecdotal evidence and expert opinions due to the lack of solid data and prospective studies. Therefore, cardiac monitoring, in patients receiving ICIs, is often not implemented by oncologists as many questions remain unanswered. Hence, the urgent need to investigate the possible short and long term cardiovascular effects of ICIs.
The investigators developed a multicentre, prospective study in which patients with a solid tumour eligible for ICI treatment will be enrolled. The study exists of routine investigations of blood parameters (troponin and (N-terminal) brain-type natriuretic peptide levels in particular) and a thorough cardiovascular follow-up on fixed time points during a period of two years. The cardiovascular follow-up consists of continuous remote patient monitoring, routine cardiology consultations including electrocardiograms, transthoracic echocardiograms, CT-scans for calcium scoring and non-invasive endothelial function tests. Associations between these blood parameters and short and long term cardiovascular irAEs will be statistically analysed.
This project will allow for a better estimate of the incidence of both short and long-term cardiovascular irAEs in a 'real world' patient population receiving ICIs. If the investigators are able to accurately predict and detect short- and long-term cardiovascular irAEs in an early (and subclinical) stage by correct implementation and interpretation of existing cardiac markers, they could be managed early on in a more effective manner.
- Conditions
- Cancer, Immune-related Adverse Event, Cardiac Abnormalities, Variable, Immune Checkpoint Inhibitor-Related Myocarditis, Diastolic Dysfunction, Atherosclerosis
- Being tested
- Cardiology consultation, Chest Computed Tomography (CT) without contrast, Non-invasive endothelial function tests, Electrocardiogram, Extra serum sample (7.5 mL)
- Keywords
- Cardio-oncology, Immune-related adverse event, Immune checkpoint inhibitor, Myocarditis, Troponin
- Medical subject headings
- Neoplasms, Atherosclerosis, Cardiotoxicity, Myocarditis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cardiology consultationProcedure or surgery
- Electrocardiogram (ECG).
- Echocardiogram: A comprehensive evaluation of systolic and diastolic function, ventricular and atrial geometry will be performed. Special attention will be given to acquire a 3D measurement of left ventricular ejection fraction (LVEF) and to perform deformation imaging of left ventricle (global longitudinal strain (GLS)). The right ventricular function will be evaluated by tricuspid annular plane systolic excursion (TAPSE) and peak systolic velocity S' derived from color coded tissue Doppler imaging (TDI). Diastolic dysfunction will be based on average E/e' ratio > 15 and left atrial (LA) area > 30 cm2.
Chest Computed Tomography (CT) without contrastDiagnostic test
Also called Cardiac CT
Calcium score. This will be performed at baseline, 12 and 24 months. The scans at 12 and 24 months will be combined, if possible, with standard of care scans for cancer treatment.
Non-invasive endothelial function testsProcedure or surgery
Also called Flow mediated dilatation (FMD), Peripheral arterial tonometry (PAT)
- FMD
- PAT
This aspect of the study will only be performed in the patients included by the Antwerp University Hospital due to organizational/practical issues.
ElectrocardiogramProcedure or surgery
Also called ECG
An ECG will be taken prior to each ICI cycle during the first three months of treatment.
Extra serum sample (7.5 mL)Diagnostic test
An extra serum sample will be taken at baseline, 3, 6, 12, 24 months and in case of sudden cardiac problems. This will subsequently be analysed to determine high-sensitivity troponin I, high-sensitivity troponin T and NT-proBNP.
| Study group | Role | What they receive |
|---|---|---|
| Cancer patients with a solid tumour eligible for treatment with immune checkpoint inhibitors | Other | Patients are treated as standard of care Receives: Procedure: Cardiology consultation; Diagnostic Test: Chest Computed Tomography (CT) without contrast; Procedure: Non-invasive endothelial function tests; Procedure: Electrocardiogram; Diagnostic Test: Extra serum sample (7.5 mL) |
What is being measured
The primary outcome is the main question the study is designed to answer.
The incidence of an elevated hs-TnT above the ULN if the baseline value was normal; or 1.5 ≥ times baseline if the baseline value was above the ULN within the first three months of treatment. The maximum measured value will be taken into account.
For the primary endpoint, the cumulative incidence of troponin elevation will be calculated with death as a competing risk. Cumulative incidences and corresponding 95% confidence intervals will be reported and a cumulative incidence plot will be used to visualize the results.
Measured: Preliminary analysis once 50 patients have reached their 3-month cardiac follow-up visit and 3 months after last patient is included.
Secondary outcomes (25)
The incidence of hs-TnT/NT-proBNP elevations at 6, 12, and 24 months.
Cumulative incidences and 95% confidence intervals, considering death as a competing event.
Measured: Through study completion, an average of 1 year
The incidence of hs-TnT/NT-proBNP elevations at baseline, 3, 6, 12, and 24 months.
Cumulative incidences and 95% confidence intervals, considering death as a competing event.
Measured: Preliminary analysis once 50 patients have reached their 3-month cardiac follow-up visit and through study completion, an average of 1 year
Evolution of hs-TnT/NT-proBNP in 24 months compared to baseline.
Linear mixed effects model with a random intercept per subject to account for the correlation measurements coming from the same individual.
Measured: Through study completion, an average of 1 year
Evolution of transthoracic 3D echocardiography parameters (dimensions, diastolic function, valvular abnormalities, LVEF, strain analysis) at baseline, 3, 6, 12, and 24 months.
Linear mixed effects model with a random intercept per subject to account for the correlation measurements coming from the same individual.
Measured: reliminary analysis once 50 patients have reached their 3-month cardiac follow-up visit and through study completion, an average of 1 year
Evolution of electrocardiography parameters (rhythm, heart axis, PQ interval, QRS duration, bundle branch block, QT interval, RR interval, pathological Q's, left ventricular hypertrophy and STT segments) at baseline, 3, 6, 12, and 24 months.
Linear mixed effects model with a random intercept per subject to account for the correlation measurements coming from the same individual.
Measured: reliminary analysis once 50 patients have reached their 3-month cardiac follow-up visit and through study completion, an average of 1 year
Association between the evolution of troponin/NT-proBNP and transthoracic echocardiography parameters at baseline, 3, 6, 12, and 24 months.
Linear mixed effects model with a random intercept per subject to account for the correlation measurements coming from the same individual.
Measured: reliminary analysis once 50 patients have reached their 3-month cardiac follow-up visit and through study completion, an average of 1 year
Association between the evolution of troponin/NT-proBNP and electrocardiography (rhythm, heart axis, PQ, QRS, bundle branch block, QT, RR, pathological Q's, left ventricular hypertrophy and STT segments) parameters at baseline, 3, 6, 12, and 24 months.
Linear mixed effects model with a random intercept per subject to account for the correlation measurements coming from the same individual.
Measured: reliminary analysis once 50 patients have reached their 3-month cardiac follow-up visit and through study completion, an average of 1 year
Cumulative incidence of cardiovascular (CV) abnormalities at 3, 6, 12, and 24 months based on the CARDIOTOX classification system of Sendón et al., with the inclusion of pericardial effusion and new arrhythmias.
Cumulative incidences and 95% confidence intervals, considering death as a competing event.
Measured: Through study completion, an average of 1 year
Association between the evolution of troponin/NT-proBNP and CV abnormalities (as classified based on the CARDIOTOX classification for myocardial injury including cardiac biomarkers, symptoms, LVEF, LA area, LVESV, GLS and diastolic function).
Joint model combining a linear mixed model for troponin and a sub-distributional proportional hazards model for the time-to-event taking into account death as a competing event for CV abnormality and MACE.
Measured: Through study completion, an average of 1 year
Cumulative incidence of MACEs at 3, 6, 12, and 24 months. MACEs were defined as the composite outcome of nonfatal stroke, nonfatal myocardial infarction, hospital admission for heart failure (HF) and cardiac revascularization, and CV death.
Cumulative incidences and 95% confidence intervals, considering death as a competing event.
Measured: Through study completion, an average of 1 year
Overall survival.
Cumulative incidences and 95% confidence intervals
Measured: reliminary analysis once 50 patients have reached their 3-month cardiac follow-up visit and through study completion, an average of 1 year
Association between the evolution of troponin/NT-proBNP and MACEs over a period of two years. Nonfatal stroke, nonfatal myocardial infarction, hospital admission for heart failure, cardiac revascularization and CV death will be combined to report MACEs.
Joint model combining a linear mixed model for troponin and a sub-distributional proportional hazards model for the time-to-event taking into account death as a competing event for CV abnormality and MACE.
Measured: Through study completion, an average of 1 year
The difference in the evolution of hs-TnT/NT-proBNP between combination therapy and monotherapy over a period of two years.
Linear mixed effects model with a random intercept per subject to account for the correlation measurements coming from the same individual. This model will be extended with patient and treatment characteristics and their interaction with time, to evaluate their impact on the evolution of these parameters.
Measured: Through study completion, an average of 1 year
The difference in the evolution of transthoracic echocardiography parameters (dimensions, diastolic function, valvular abnormalities, LVEF, strain analysis) between combination therapy and monotherapy over a period of two years.
Linear mixed effects model with a random intercept per subject to account for the correlation measurements coming from the same individual. This model will be extended with patient and treatment characteristics and their interaction with time, to evaluate their impact on the evolution of these parameters.
Measured: Through study completion, an average of 1 year
The difference in the evolution of electrocardiography parameters (rhythm, heart axis, PQ, QRS, bundle branch block, QT, RR, pathological Q's, left ventricular hypertrophy and STT segments) between combination therapy and monotherapy.
Linear mixed effects model with a random intercept per subject to account for the correlation measurements coming from the same individual. This model will be extended with patient and treatment characteristics and their interaction with time, to evaluate their impact on the evolution of these parameters.
Measured: Through study completion, an average of 1 year
Association between patient characteristics (demographics, medical history, current oncological disease, prior cancer history, prior/concomitant medication and other relevant parameters) and troponin.
Linear mixed effects model with a random intercept per subject to account for the correlation measurements coming from the same individual. This model will be extended with patient and treatment characteristics and their interaction with time, to evaluate their impact on the evolution of these parameters.
Measured: Through study completion, an average of 1 year
Association between patient characteristics (demographics, medical history, current oncological disease, prior cancer history, prior/concomitant medication and other relevant parameters) and NT-proBNP.
Linear mixed effects model with a random intercept per subject to account for the correlation measurements coming from the same individual. This model will be extended with patient and treatment characteristics and their interaction with time, to evaluate their impact on the evolution of these parameters.
Measured: Through study completion, an average of 1 year
Agreement between hs-TnT and hs-TnI levels at baseline, 3, 6, 12, and 24 months.
Bland-Altman curves and intraclass correlation coefficient (ICC) based on a two-way mixed effects model. The ICC and 95% confidence interval will be reported.
Measured: reliminary analysis once 50 patients have reached their 3-month cardiac follow-up visit and through study completion, an average of 1 year
The proportion of severe immune-related non-CV toxicities (grades 3-5).
Proportions and 95% confidence interval
Measured: Through study completion, an average of 1 year
Association between the evolution of troponin/NT-proBNP and severe immune-related non-CV toxicities (grades 3-5, e.g. pneumonitis, colitis, thyroiditis, etc. according to the CTCAE criteria).
Linear mixed effects model with a random intercept per subject to account for the correlation measurements coming from the same individual. This model will be extended with patient and treatment characteristics and their interaction with time, to evaluate their impact on the evolution of these parameters.
Measured: Through study completion, an average of 1 year
Association between the evolution of troponin/NT-proBNP and overall survival.
Joint model combining a linear mixed model for troponin and a sub-distributional proportional hazards model for the time-to-event taking into account death as a competing event for CV abnormality and MACE.
Measured: Through study completion, an average of 1 year
Association between the evolution of troponin and diastolic function (based on the recommendations listed in https://doi.org/10.1016/j.echo.2016.01.011, mitral inflow, tissue doppler imaging parameters).
Linear mixed effects model with a random intercept per subject to account for the correlation measurements coming from the same individual. This model will be extended with patient and treatment characteristics and their interaction with time, to evaluate their impact on the evolution of these parameters.
Measured: Through study completion, an average of 1 year
Calcium score at baseline, 12 months, and 24 months.
Proportions and 95% confidence interval
Measured: Through study completion, an average of 1 year
Peripheral vascular function at baseline, 3 months, 6 months, 12 months and 24 months.
Flow mediated dilatation: dilatation % from baseline to maximal post-occlusion diameter.
Peripheral arterial tonometry ratio: based on the response to reactive hyperemia using post and pre-occlusion values
Measured: Through study completion, an average of 1 year
Association between the evolution of troponin and calcium score.
Flow mediated dilatation: dilatation % from baseline to maximal post-occlusion diameter.
Peripheral arterial tonometry ratio: based on the response to reactive hyperemia using post and pre-occlusion values
Measured: Through study completion, an average of 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jan 2023
- Study start7 Jan 2022
- Primary completion12 Jul 2024
- Study completion12 Jul 2024
Why it stopped: Study was stopped due to negative preliminary analysis, slow recruitment (105 patients over 2,5 years), lack of funding, need for more centers, and the changing treatment landscape (approval of ICIs in combination with other cancer treatments).
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for CancerStudies 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 105 participants (actual)
Sponsor and investigators
- Lead sponsor
- Algemeen Ziekenhuis Maria Middelares
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Prof. Dr. Christof Vulsteke, Algemeen Ziekenhuis Maria Middelares
- Investigators
- Christof Vulsteke, Prof, Principal investigator, Algemeen Ziekenhuis Maria Middelares
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05699915
- Sponsor's protocol ID
- MMS.2021.058
- Acronym
- CAVACI
- Status last verified
- Jan 2025
- First submitted
- 9 Dec 2022
- Last updated
- 30 Jan 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Delombaerde D, De Sutter J, Croes L, Vervloet D, Moerman V, Van de Veire N, Willems AM, Wouters K, Peeters M, Prenen H, Vulsteke C. Extensive CArdioVAscular Characterization and Follow-Up of Patients Receiving Immune Checkpoint Inhibitors: A Prospective Multicenter Study. Pharmaceuticals (Basel). 2023 Apr 20;16(4):625. doi: 10.3390/ph16040625.
PubMed 37111382
Study at a glance
From the registry record, last updated by the sponsor on 30 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Extensive CArdioVAscular Characterization and Follow-up of Patients Receiving Immune Checkpoint Inhibitors: a Prospective Multicentre Study
- ClinicalTrials.gov ID
- NCT05699915
- Acronym / sponsor ID
- CAVACI / MMS.2021.058
- Conditions
- Cancer, Immune-related Adverse Event, Cardiac Abnormalities, Variable, Immune Checkpoint Inhibitor-Related Myocarditis, Diastolic Dysfunction, Atherosclerosis
- Keywords
- Cardio-oncology, Immune-related adverse event, Immune checkpoint inhibitor, Myocarditis, Troponin
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study was stopped due to negative preliminary analysis, slow recruitment (105 patients over 2,5 years), lack of funding, need for more centers, and the changing treatment landscape (approval of ICIs in combination with other cancer treatments).
- Enrolment
- 105 participants (actual)
- Lead sponsor
- Algemeen Ziekenhuis Maria MiddelaresUniversity, hospital or other
- Study start
- 7 Jan 2022 (actual)
- Primary completion
- 12 Jul 2024 (actual)
- Study completion
- 12 Jul 2024 (actual)
- First posted
- 26 Jan 2023 (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.
The goal of this prospective, multicentre study is to investigate short- and long-term cardiovascular effects in cancer patients treated with immune checkpoint inhibitors (ICIs).
The main question[s] it aims to answer are:
- To investigate troponin and NT-proBNP values in patients receiving ICIs and their association with ICI-induced CV abnormalities and MACEs.
- Study the calcium score, systolic, and diastolic (dys)function.
- Evaluate associations between patient/disease characteristics / transthoracic echocardiography parameters / electrocardiography parameters and troponin / NT-proBNP levels.
Participants will be closely monitored by performing the following additional visits and testing:
- Chest CT scan prior to treatment start, after 12 and 24 months.
- Consultation with a cardiologist at baseline, 3, 6, 12 and 24 months, who will perform an electrocardiogram and echocardiogram.
- One additional blood sample prior to treatment start, after 3, 6, 12 and 24 months. An extra blood sample could be taken in case of sudden heart problems.
- Non-invasive endothelial function tests prior to treatment start, after 12 and 24 months.
Detailed description
The increasing use of immune checkpoint inhibitors (ICIs) in the treatment of both advanced and early stages of various malignancies has resulted in a substantial increase in the incidence of cardiovascular immune related adverse events (irAEs). The current guidelines are based on anecdotal evidence and expert opinions due to the lack of solid data and prospective studies. Therefore, cardiac monitoring, in patients receiving ICIs, is often not implemented by oncologists as many questions remain unanswered. Hence, the urgent need to investigate the possible short and long term cardiovascular effects of ICIs.
The investigators developed a multicentre, prospective study in which patients with a solid tumour eligible for ICI treatment will be enrolled. The study exists of routine investigations of blood parameters (troponin and (N-terminal) brain-type natriuretic peptide levels in particular) and a thorough cardiovascular follow-up on fixed time points during a period of two years. The cardiovascular follow-up consists of continuous remote patient monitoring, routine cardiology consultations including electrocardiograms, transthoracic echocardiograms, CT-scans for calcium scoring and non-invasive endothelial function tests. Associations between these blood parameters and short and long term cardiovascular irAEs will be statistically analysed.
This project will allow for a better estimate of the incidence of both short and long-term cardiovascular irAEs in a 'real world' patient population receiving ICIs. If the investigators are able to accurately predict and detect short- and long-term cardiovascular irAEs in an early (and subclinical) stage by correct implementation and interpretation of existing cardiac markers, they could be managed early on in a more effective manner.
Study design
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Cancer patients with a solid tumour eligible for treatment with immune checkpoint inhibitors | Other | Procedure: Cardiology consultation, Diagnostic Test: Chest Computed Tomography (CT) without contrast, Procedure: Non-invasive endothelial function tests, Procedure: Electrocardiogram, Diagnostic Test: Extra serum sample (7.5 mL)Patients are treated as standard of care |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Have a solid tumour and will receive one of the following therapies based on current evidence based clinical guidelines: anti-programmed cell death protein-1 (PD-1), anti-programmed cell death ligand-1 (PD-L1) and/or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) therapy
- Be literate in Dutch or English
Key exclusion criteria (5 listed)
- Prior treatment with immunotherapy (immune checkpoint inhibitors, T-cell transfer therapy, cancer treatment vaccines or immune system modulators).
- Patients who will receive ICIs in combination with an additional systemic anti-cancer regimen (chemotherapy, tyrosine kinase inhibitors,…).
- Having a known history of human immunodeficiency virus (HIV) infection.
- Having a known history of hepatitis B (defined as hepatitis B surface antigen [HBsAg] reactive) or known active hepatitis C virus (defined as detectable RNA via qualitative nucleic acid testing) infection.
- Having a diagnosis of immunodeficiency or is receiving chronic/active systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent)
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 |
|---|---|---|
| Cardiology consultation* Electrocardiogram (ECG). * Echocardiogram: A comprehensive evaluation of systolic and diastolic function, ventricular and atrial geometry will be performed. Special attention will be given to acquire a 3D measurement of left ventricular ejection fraction (LVEF) and to perform deformation imaging of left ventricle (global longitudinal strain (GLS)). The right ventricular function will be evaluated by tricuspid annular plane systolic excursion (TAPSE) and peak systolic velocity S' derived from color coded tissue Doppler imaging (TDI). Diastolic dysfunction will be based on average E/e' ratio > 15 and left atrial (LA) area > 30 cm2. | Procedure or surgery | Cancer patients with a solid tumour eligible for treatment with immune checkpoint inhibitors |
| Chest Computed Tomography (CT) without contrastAlso: Cardiac CTCalcium score. This will be performed at baseline, 12 and 24 months. The scans at 12 and 24 months will be combined, if possible, with standard of care scans for cancer treatment. | Diagnostic test | Cancer patients with a solid tumour eligible for treatment with immune checkpoint inhibitors |
| Non-invasive endothelial function testsAlso: Flow mediated dilatation (FMD), Peripheral arterial tonometry (PAT)* FMD * PAT This aspect of the study will only be performed in the patients included by the Antwerp University Hospital due to organizational/practical issues. | Procedure or surgery | Cancer patients with a solid tumour eligible for treatment with immune checkpoint inhibitors |
| ElectrocardiogramAlso: ECGAn ECG will be taken prior to each ICI cycle during the first three months of treatment. | Procedure or surgery | Cancer patients with a solid tumour eligible for treatment with immune checkpoint inhibitors |
| Extra serum sample (7.5 mL)An extra serum sample will be taken at baseline, 3, 6, 12, 24 months and in case of sudden cardiac problems. This will subsequently be analysed to determine high-sensitivity troponin I, high-sensitivity troponin T and NT-proBNP. | Diagnostic test | Cancer patients with a solid tumour eligible for treatment with immune checkpoint inhibitors |
Primary outcome
The incidence of an elevated hs-TnT above the ULN if the baseline value was normal; or 1.5 ≥ times baseline if the baseline value was above the ULN within the first three months of treatment. The maximum measured value will be taken into account.
Time frame: Preliminary analysis once 50 patients have reached their 3-month cardiac follow-up visit and 3 months after last patient is included.
For the primary endpoint, the cumulative incidence of troponin elevation will be calculated with death as a competing risk. Cumulative incidences and corresponding 95% confidence intervals will be reported and a cumulative incidence plot will be used to visualize the results.
25 secondary outcomes
The incidence of hs-TnT/NT-proBNP elevations at 6, 12, and 24 months.
Time frame: Through study completion, an average of 1 year
The incidence of hs-TnT/NT-proBNP elevations at baseline, 3, 6, 12, and 24 months.
Time frame: Preliminary analysis once 50 patients have reached their 3-month cardiac follow-up visit and through study completion, an average of 1 year
Evolution of hs-TnT/NT-proBNP in 24 months compared to baseline.
Time frame: Through study completion, an average of 1 year
Evolution of transthoracic 3D echocardiography parameters (dimensions, diastolic function, valvular abnormalities, LVEF, strain analysis) at baseline, 3, 6, 12, and 24 months.
Time frame: reliminary analysis once 50 patients have reached their 3-month cardiac follow-up visit and through study completion, an average of 1 year
Evolution of electrocardiography parameters (rhythm, heart axis, PQ interval, QRS duration, bundle branch block, QT interval, RR interval, pathological Q's, left ventricular hypertrophy and STT segments) at baseline, 3, 6, 12, and 24 months.
Time frame: reliminary analysis once 50 patients have reached their 3-month cardiac follow-up visit and through study completion, an average of 1 year
Association between the evolution of troponin/NT-proBNP and transthoracic echocardiography parameters at baseline, 3, 6, 12, and 24 months.
Time frame: reliminary analysis once 50 patients have reached their 3-month cardiac follow-up visit and through study completion, an average of 1 year
Association between the evolution of troponin/NT-proBNP and electrocardiography (rhythm, heart axis, PQ, QRS, bundle branch block, QT, RR, pathological Q's, left ventricular hypertrophy and STT segments) parameters at baseline, 3, 6, 12, and 24 months.
Time frame: reliminary analysis once 50 patients have reached their 3-month cardiac follow-up visit and through study completion, an average of 1 year
Cumulative incidence of cardiovascular (CV) abnormalities at 3, 6, 12, and 24 months based on the CARDIOTOX classification system of Sendón et al., with the inclusion of pericardial effusion and new arrhythmias.
Time frame: Through study completion, an average of 1 year
Association between the evolution of troponin/NT-proBNP and CV abnormalities (as classified based on the CARDIOTOX classification for myocardial injury including cardiac biomarkers, symptoms, LVEF, LA area, LVESV, GLS and diastolic function).
Time frame: Through study completion, an average of 1 year
Cumulative incidence of MACEs at 3, 6, 12, and 24 months. MACEs were defined as the composite outcome of nonfatal stroke, nonfatal myocardial infarction, hospital admission for heart failure (HF) and cardiac revascularization, and CV death.
Time frame: Through study completion, an average of 1 year
Overall survival.
Time frame: reliminary analysis once 50 patients have reached their 3-month cardiac follow-up visit and through study completion, an average of 1 year
Association between the evolution of troponin/NT-proBNP and MACEs over a period of two years. Nonfatal stroke, nonfatal myocardial infarction, hospital admission for heart failure, cardiac revascularization and CV death will be combined to report MACEs.
Time frame: Through study completion, an average of 1 year
The difference in the evolution of hs-TnT/NT-proBNP between combination therapy and monotherapy over a period of two years.
Time frame: Through study completion, an average of 1 year
The difference in the evolution of transthoracic echocardiography parameters (dimensions, diastolic function, valvular abnormalities, LVEF, strain analysis) between combination therapy and monotherapy over a period of two years.
Time frame: Through study completion, an average of 1 year
The difference in the evolution of electrocardiography parameters (rhythm, heart axis, PQ, QRS, bundle branch block, QT, RR, pathological Q's, left ventricular hypertrophy and STT segments) between combination therapy and monotherapy.
Time frame: Through study completion, an average of 1 year
Association between patient characteristics (demographics, medical history, current oncological disease, prior cancer history, prior/concomitant medication and other relevant parameters) and troponin.
Time frame: Through study completion, an average of 1 year
Association between patient characteristics (demographics, medical history, current oncological disease, prior cancer history, prior/concomitant medication and other relevant parameters) and NT-proBNP.
Time frame: Through study completion, an average of 1 year
Agreement between hs-TnT and hs-TnI levels at baseline, 3, 6, 12, and 24 months.
Time frame: reliminary analysis once 50 patients have reached their 3-month cardiac follow-up visit and through study completion, an average of 1 year
The proportion of severe immune-related non-CV toxicities (grades 3-5).
Time frame: Through study completion, an average of 1 year
Association between the evolution of troponin/NT-proBNP and severe immune-related non-CV toxicities (grades 3-5, e.g. pneumonitis, colitis, thyroiditis, etc. according to the CTCAE criteria).
Time frame: Through study completion, an average of 1 year
Association between the evolution of troponin/NT-proBNP and overall survival.
Time frame: Through study completion, an average of 1 year
Association between the evolution of troponin and diastolic function (based on the recommendations listed in https://doi.org/10.1016/j.echo.2016.01.011, mitral inflow, tissue doppler imaging parameters).
Time frame: Through study completion, an average of 1 year
Calcium score at baseline, 12 months, and 24 months.
Time frame: Through study completion, an average of 1 year
Peripheral vascular function at baseline, 3 months, 6 months, 12 months and 24 months.
Time frame: Through study completion, an average of 1 year
Association between the evolution of troponin and calcium score.
Time frame: Through study completion, an average of 1 year
Results and safety
The study was stopped early (reason given: Study was stopped due to negative preliminary analysis, slow recruitment (105 patients over 2,5 years), lack of funding, need for more centers, and the changing treatment landscape (approval of ICIs in combination with other cancer treatments).). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jan 2025.
- Derived from this study: PubMed 37111382Delombaerde D, De Sutter J, Croes L, Vervloet D, Moerman V, Van de Veire N, Willems AM, Wouters K, Peeters M, Prenen H, Vulsteke C. Extensive CArdioVAscular Characterization and Follow-Up of Patients Receiving Immune Checkpoint Inhibitors: A Prospective Multicenter Study. Pharmaceuticals (Basel). 2023 Apr 20;16(4):625. doi: 10.3390/ph16040625.
- Individual participant dataSharing planned: No
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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. This study is not recruiting at the moment.
Christof Vulsteke, Prof principal investigator
Algemeen Ziekenhuis Maria Middelares
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Cardiology consultation, Chest Computed Tomography (CT) without contrast and Non-invasive endothelial function tests in people with Cancer and Immune-related Adverse Event, run by Algemeen Ziekenhuis Maria Middelares at 4 sites in Belgium.
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 2 inclusion and 5 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: stopped early, as of the sponsor's last update on 30 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Belgium. 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?
The study was stopped early (reason given: Study was stopped due to negative preliminary analysis, slow recruitment (105 patients over 2,5 years), lack of funding, need for more centers, and the changing treatment landscape (approval of ICIs in combination with other cancer treatments).). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The incidence of an elevated hs-TnT above the ULN if the baseline value was normal; or 1.5 ≥ times baseline if the baseline value was above the ULN within the first three months of treatment. The maximum measured value will be taken into account. (time frame: Preliminary analysis once 50 patients have reached their 3-month cardiac follow-up visit and 3 months after last patient is included.). 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 NCT05699915, which also lists 1 linked publication.
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 30 Jan 2025.