Statins to Prevent Immune checkpoint inhibitor-induced pRogression of AtheroscLerosis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14], Diseases [C] - Neoplasms [C04]

Decision date (initial)

2025-05-12

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-511127-33-00

ClinicalTrials.gov

NCT06785974

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

The main objective of this trial is to study whether atorvastatin prevents accelerated progression of atherosclerosis during ICI therapy, as measured in the descending thoracic aorta between the intervention and control group.

Secondary objectives 6

1. To investigate whether atorvastatin can prevent ICI-induced increase in total and calcified plaque volume in the thoracic aorta after ICI treatment initiation.
2. To investigate whether atorvastatin can prevent progression of total, non-calcified and calcified plaque volume in the coronary arteries after starting ICI therapy
3. To investigate whether atorvastatin can prevent ICI-induced increase in epicardial fat volume
4. To investigate whether atorvastatin can prevent ICI-induced vascular endo-thelial dysfunction
5. To assess the quality of life in patients receiving ICI + statins vs. ICI + placebo
6. To investigate the difference in adverse events in patients receiving ICI + statins vs. ICI + placebo.

Conditions and MedDRA coding

Atherosclerosis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Patients with melanoma who are scheduled to receive ICI therapy (nivolumab, pembrolizumab, ipilimumab or combination therapy) according to standard-of-care.
2. Age ≥ 18 years
3. Able to understand the written information and able to give informed consent
4. Presence of thoracic aortic atherosclerosis at baseline, defined as: presence of vessel wall calcifications in the thoracic aorta, and/or vessel wall irregularity of the thoracic aorta, and/or presence of an apparent thickening of the vessel wall with a hypodense aspect in the thoracic aorta

Exclusion criteria 7

1. Baseline statins use or previously reported statin intolerance
2. Pregnancy or lactation
3. Current or recent (≤1 year) history of alcohol (≥3 consumptions/day) or drug abuse
4. Contra-indication for statin therapy, including: active liver disease, including ALT/AST levels ≥ 3x ULN, and/or (History of) myopathy, and/or congenital muscular disorder, and/or history of (drug-induced) rhabdomyolysis, and/or history of drug-induced myopathy with elevated creatine kinase (CK)
5. Use of essential medication with (potential) interactions with atorvastatin, including: Strong CYP3A4 inhibitors (such as clarithromycin, ciclosporin, itraconazole, ketoconazole, voriconazole, posaconazole, HCV agents, HIV protease inhibitors), and/or BCRP inhibitors (such as elbasvir and grazoprevir), and/or Fibrates (including gemfibrozil)
6. Indication for statin treatment according to the 2024 Dutch multi-disciplinary CVRM guidelines
7. Significant obstructive coronary artery disease (>50% LM stenosis or >70% of proximal LAD, Cx or RCA segment, or multivessel significant more distal disease)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Annualized percentage change in non-calcified atherosclerotic plaque volume in the descending thoracic aorta in the intervention versus the control group.

Secondary endpoints 7

1. Annualized percentage change in total and calcified atherosclerotic plaque volume in the thoracic aorta in the intervention versus the control group
2. Annualized percentage change in total, non-calcified and calcified coronary artery atherosclerotic plaque volume in the intervention versus the control group.
3. Annualized change in coronary calcification score (Agatston score) and MESA score in the intervention versus the control group.
4. Annualized change in epicardial fat volume in the intervention versus the control group p
5. Difference in reactive hyperaemia index as a marker of endothelial dysfunction using peripheral arterial tonometry (EndoPAT) between intervention and control group.
6. Difference in quality of life between intervention and control group at baseline, 3 months, 6 months and 1 year after the start of ICI therapy
7. Differences in the number of adverse events between intervention and control group during the first year after start of ICI therapy, graded according to CTCAE criteria, version 5.0.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

Sponsor organisation

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

Address

Dr. Molewaterplein 40

City

Rotterdam

Postcode

3015 GD

Country

Netherlands

Scientific contact point

Organisation

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

Contact name

Jorie Versmissen

Public contact point

Organisation

Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)

Contact name

Tom Uyl

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 8 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications