Extensive CArdioVAscular Characterization and Follow-up of Patients Receiving Immune Checkpoint Inhibitors (CAVACI)

Algemeen Ziekenhuis Maria Middelares

Status

Terminated

Conditions

Cardiotoxicity

Immune Checkpoint Inhibitor-Related Myocarditis

Diastolic Dysfunction

Cardiac Abnormalities, Variable

Immune-related Adverse Event

Cancer

Atherosclerosis

Treatments

Procedure: Non-invasive endothelial function tests

Diagnostic Test: Extra serum sample (7.5 mL)

Procedure: Cardiology consultation

Procedure: Electrocardiogram

Diagnostic Test: Chest Computed Tomography (CT) without contrast

Study type

Interventional

Funder types

Other

Identifiers

NCT05699915

MMS.2021.058

Details and patient eligibility

About

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.

Full 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.

Enrollment

105 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

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

Exclusion criteria

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)