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Prospective Exploration of Vascular Complications Associated With the Use of Immune Checkpoint Inhibitors

NCT07535944 · Status: NOT_YET_RECRUITING · Type: OBSERVATIONAL · Enrollment: 200

Last updated 2026-04-17

No results posted yet for this study

Summary

The development of immune checkpoint inhibitors (ICIs) has revolutionized the management of many oncological diseases, and their use continues to increase. ICIs are monoclonal antibodies that target immune checkpoints such as PD-1 (programmed cell death protein 1, as seen in nivolumab, pembrolizumab, and cemiplimab), PD-L1 (programmed cell death protein 1 ligand, as seen in atezolizumab, avelumab, and durvalumab), CTLA-4 (cytotoxic T-lymphocyte antigen 4, as seen in ipilimumab and tremelimumab), or LAG-3 (lymphocyte-activating gene 3, as seen in relatlimab), which play a crucial role in immune tolerance to cancer cells.

However, the surge in ICI prescriptions has been accompanied by the occurrence of numerous side effects, some of which are severe or even fatal. ICIs have a different toxicity spectrum than conventional chemotherapy, and most toxicities result from excessive immunity against different organs.

This immune-mediated toxicity can affect various organ systems, including the heart and blood vessels. Pharmacovigilance data from clinical trials conducted by Bristol-Myers Squibb, which marketed ipilimumab (anti-CTLA-4) and nivolumab (anti-PD1), revealed 18 cases (0.09%) of myocarditis among 20,594 subjects.

While cardiac complications induced by immune checkpoint inhibitors (ICIs), particularly autoimmune myocarditis, are widely described, the impact of these treatments on the vascular system remains poorly understood. However, a variety of vascular complications have been reported, ranging from vasculitis of large, medium, and small vessels to a possible increase in arterial thrombotic events, ischemic strokes, and acute coronary syndromes.

The incidence of vasculitis appears to be between 1% and 2% of patients treated with immune checkpoint inhibitors (ICIs). This is emerging as a significant signal in various pharmacovigilance studies, suggesting the involvement of immune checkpoint derepression in the pathophysiology of vasculitis. A translational study demonstrated the major role of CTLA-4 in the pathophysiology of giant cell arteritis (GCA), although the precise mechanisms involved remain to be determined. Therefore, a specific immune environment could promote the development of vasculitis, a phenomenon reproduced by ICI administration.

The increase in arterial thrombotic vascular events was primarily observed in a matched cohort study, which showed a threefold increased risk of arterial thrombotic vascular events following the initiation of ICI therapy. These thrombotic events would coincide with the acceleration of atherosclerosis in patients treated with ICIs. This "accelerated" atherosclerosis could be linked to inflammatory changes within the plaques, causing plaque destabilization or rupture. It is also unreasonable to rule out the possibility that the accelerated atherosclerosis is related to the development of vasculitis in these patients.

Conditions

  • Vascular Complications

Interventions

OTHER

Evaluation of the vascular impact of ICIs (Immune Checkpoint Inhibitors)

A multidisciplinary clinical-biological approach to research involving the clinical pharmacology department for the creation of the popmeter (population pharmacokinetic/pharmacodynamic analysis tool), the CIC-CRB1404 for the management of biological samples, the dermatology oncology department (Dr. Raphael Janela) for the recruitment and monitoring of volunteers, and the Inserm U1096 EnVI laboratory for the measurement of lymphocyte and monocyte activation markers.

Sponsors & Collaborators

  • University Hospital, Rouen

    lead OTHER

Principal Investigators

  • Jérémy JB BELLIEN, Professor · Univerity Rouen Hospital

Eligibility

Min Age
18 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2026-06-01
Primary Completion
2028-08-01
Completion
2031-06-01

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Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT07535944 on ClinicalTrials.gov