Adverse Myocardial and Vascular Side Effects of Immune Checkpoint Inhibitors

Completed

• Conditions: Cancer; Cardiovascular Abnormalities; Immune Defect
• Interventions: Diagnostic Test: Cardiac MRI; Device: Smart cloth; Other: Biobanking

• Registration Number: NCT04586894
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

Brief Summary

Our knowledge on cardiovascular side effects of immune checkpoint inhibitors (ICIs) is restricted to this date to observational retrospective data (mainly case series and pharamcovigilance analysis). We aim at assessing the incidence of cardiovascular adverse side effects of ICIs by means of a prospective interventional single centre study using multiple biomarkers.

Detailed Description

Immune checkpoint inhibitors (ICIs) are drastically improving cancer prognosis. Cardiovascular adverse side effects of ICIs are though to be rare but may be responsible for \~50% death rates.

Prospective screening for cardiovascular and muscular immune related side effects has not been undertaken independently from the industry.

The aim is to describe the incidence of these side effects by means of serial assessment in patients undergoing ICI therapy for cancer. Biomarkers as ECG, echocardiography, cardiac magnetic resonance imaging and long-term ECG monitoring will be undertaken at inclusion (before ICI therapy is started), and during the first cycle treatments and at 6 months follow-up.

Mean endpoint encompasses cardiovascular and muscular adverse side effects between the 2nd and the 3rd ICI cycle. Secondary endpoints include cardiovascular and muscular adverse side effects at 6 months follow-up, and the incidence of individual side effects.

4 ancillary studies based on patients' blood biobanking are also planned. Their objectives are:

* to assess sensitivity of heart failure biomarkers in predicting cardiovascular events under ICI,

* to assess sensitivity of cytokine biomarkers in predicting cardiovascular events under ICI,

* to bank cells to induce cardiomyocytes from stem cells

* to bank DNA to identify genetic factors related to occurrence of cardiovascular events under ICI

Study Timeline

• Study First Submitted: 2020-10-07
• Study First Submitted QC: 2020-10-07
• Study First Posted: 2020-10-14
• Study Start: 2020-11-06
• Primary Completion: 2022-02-01
• Study Completion: 2022-07-01
• Status Verified: 2023-06
• Last Update Submitted: 2023-06-07
• Last Update Posted: 2023-06-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

• prescribed treatment by immune checkpoint inhibitors (ICI) for cancer

Exclusion Criteria

• previous treatment by any ICI
• any contraindication to cardiac resonance magnetic imaging
• contraindication to gadoteric acid, meglumin or any gadolinium-based contrast agent
• pace maker or automated implantable defibrilator
• pregnancy, breastfeeding
• women of childbearing potential who do not use one of the following methods of birth control: hormonal contraception or intrauterine device or bilateral tubal occlusion
• patient under legal protection
• renal failure defined by creatinine clearance <30ml/min/m² (CKD-EPI)
• current participation or exclusion period of another interventional clinical study

Exclusion Criteria for ancillary studies:

• hemoglobinemia < 9 g/dl

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Patients	Smart cloth	-
Patients	Biobanking	-
Patients	Cardiac MRI	-

Primary Outcome Measures

Name	Time	Method
Number of patients with major cardiovascular advserse drug reactions	6 weeks	Incidence of a composite endpoint including myocarditis, pericarditis, acute coronary syndrome, acute heart failure, subclinial cardio-toxicity, high degree conduction abormalities or ventricular sustained arrythmias, cardiovascular death.

Secondary Outcome Measures

Name	Time	Method
Number of patients with major cardiovascular advserse drug reactions	6 months	Incidence of a composite endpoint including myocarditis, pericarditis, acute coronary syndrome, acute heart failure, subclinial cardio-toxicity, high degree conduction abormalities or ventricular sustained arrythmias, cardiovascular death.
Number of patients with other cardiovascular advserse drug reactions	6 weeks and 6 months	Incidence of a composite endpoint including vasculitis or myositis.
Number of patients with isolated CMR abnormalities	6 weeks and 6 months	Serial assessment
Number of patients with rhythm abnormalities that do not fullfill major advsere event criteria	6 weeks and 6 months	Burden of extrasystole, low degree conduction disorders
Risk factors for cardiovascular adverse drug event	6 weeks and 6 months	Characterization of risk predictors for occurrence of cardiovascular adverse drug event, among the following: socio-demographic characteristics, oncologic characteristics, previous treatments, serum biomarkers, patient assessment on ESC-SCORE and ACC/AHA ASCVD risk scoring systems, immune status, cardiac characteristics on imaging.

Trial Locations

Locations (1)

AP-HP - Hôpital européen Georges-Pompidou; 🇫🇷 Paris, France