AtherosclerosisPhase 4SPIRALNCT06785974
Statins to Prevent Immune Checkpoint Inhibitor-induced PRogression of AtherosLerosis
A Phase 4 study testing Atorvastatin in people with Atherosclerosis and Melanoma, run by Erasmus Medical Center at 1 site in Netherlands.
Trial summary
The goal of this interventional study is to test whether atorvastatin prevents accelerated progression of atherosclerosis in melanoma patients who receive immune checkpoint inhibitor (ICI) therapy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Atherosclerosis, Melanoma, Immune-related Adverse Event
- What is being tested?
- Atorvastatin
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 140 participants
- Where
- 1 siteNetherlands
- Study dates
- Feb 2025to Feb 2030
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
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
- In order to be eligible to participate in this study, a subject must meet all of the following criteria:
- Age ≥ 18 years
- Able to understand the written information and able to give informed consent
- Melanoma diagnosis with planned ICI treatment according to standard of care (nivolumab, pembrolizumab, monotherapy or combination therapy with ipilimumab)
- Presence of atherosclerosis in the descending thoracic aorta at baseline.
Who cannot join
- Pregnancy or lactation
- Baseline statin use or previously reported statin intolerance
- Current or recent (≤1 year) history of alcohol or drug abuse
- Contra-indication for statin therapy, including:
- Active liver disease, including ALT/AST levels ≥ 3x ULN
- (History of) myopathy Congenital muscular disorder History of (drug-induced) rhabdomyolysis History of drug-induced myopathy with elevated creatine kinase (CK)
Show all 13Show fewer
- Severe kidney failure (creatinine clearance < 30 ml/min)
- Use of essential medication with (potential) interactions with atorvastatin, including:
- strong CYP3A4 inhibitors such as clarithromycin, ciclosporin, itraconazol, ketoconazole, voriconazol, posconazol, HCV agents, HIV protease inhibitors
- BCRP inhibitors such as elbasvir and grazoprevir
- Fibrates (including gemfibrozil)
- Life expectancy < 12 months
- High MESA-score at baseline
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Netherlands1 site
Erasmus Universitair Medisch Cetrum Rotterdam
Rotterdam, South Holland, 3015GD
Jorie Versmissen, MD, PhD, j.versmissen@erasmusmc.nl
Tom Uyl, MD, t.uyl@erasmusmc.nl
About this study
The goal of this interventional study is to test whether atorvastatin prevents accelerated progression of atherosclerosis in melanoma patients who receive immune checkpoint inhibitor (ICI) therapy. The main questions it aims to answer are:
- difference in percentage growth of total atherosclerotic plaque volume (+ calcified and non-calcified plaque volume) in the descending thoracic segment of the aorta
- difference in percentage growth of total atherosclerotic plaque volume (+ calcified and non-calcified plaque volume) in coronary arteries.
Researchers will compare patients that receive ICI-therapy and atorvastatin with patients that receive ICI-therapy + placebo to see if atorvastatin will prevent accelerated ICI induced plaque growth.
Read the detailed description
Rationale: Immune checkpoint inhibitors (ICIs) are often highly effective anti-cancer therapies but predispose patients receiving this treatment to cardiovascular disease and thrombotic events. One of the mechanisms by which ICIs increase cardiovascular risk is by stimulation of inflammation and atherosclerosis. Statins (e.g., atorvastatin) are frequently prescribed and effective anti-atherogenic agents, which could provide protective effects on the cardiovascular system in this patient population whilst and after receiving ICI, minimizing cardiovascular sequelae.
The objective of this study is to study if addition of atorvastatin prevents accelerated progression of atherosclerosis during ICI therapy. In addition, the investigators would like to study the effects of atorvastatin during ICI therapy on endothelial function, epicardial fat volume, and hemostatic and inflammatory parameters.
The main study endpoint is the difference in percentage growth of total atherosclerotic plaque volume in the descending thoracic segment of the aorta between intervention and control group, expressed in indexed percentage growth /year.
Secondary endpoints are differences in non-calcified and calcified plaque volume in the thoracic arteries and coronary arteries, epicardial fat volume, endothelial function, and quality of life. Exploratory endpoints include effect on hemostatic and inflammation markers, lipid levels, progression free survival, event free survival, and overall survival.
Trial design Placebo controlled prospective randomised controlled trial.
Trial population Melanoma patients who are scheduled to receive ICI therapy (nivolumab, pembrolizumab, or a combination of anti-PD1/ipilimumab; (neo)adjuvant, irresectable or metastasized melanoma) according to standard-of-care who are also eligible to initiate statin therapy.
The intervention group receives atorvastatin 20mg daily together with ICI therapy. The control group receives placebo together with ICI therapy.
Both groups will undergo two coronary and thoracic CT-scans. In addition, blood withdrawal will take place fourthly during the study. Furthermore, endothelial function will be assessed by means of the EndoPAT device at baseline and after one year of follow-up.
Ethical considerations relating to the clinical trial including the expected benefit to the individual subject or group of patients represented by the trial subjects as well as the nature and extent of burden and risks: Patients in the intervention group will receive atorvastatin, of which safety and tolerability will be carefully monitored. Coronary atherosclerosis will be assessed via two coronary CT-scans, yielding a total limited extra radiation exposure of 4-10mSv. Blood withdrawal will be combined with regular blood withdrawal time points for standard care or will be withdrawn from the intravenous catheter for ICI administration. Vascular endothelial dysfunction will be assessed via Endothelial Peripheral Arterial Tonometry (EndoPAT) by recording finger arterial pulsatile volume change. This non-invasive method forms a minimal extra burden for participating patients. The investigators hypothesize that atorvastatin prevents accelerated progression of atherosclerosis and ameliorates ICI-induced vascular endothelial dysfunction.
- Conditions
- Atherosclerosis, Melanoma, Immune-related Adverse Event
- Being tested
- Atorvastatin, Placebo
- Keywords
- Statin, Immune Checkpoint Inhibitor
- Medical subject headings
- Atherosclerosis, Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AtorvastatinDrug
Also called Lipitor, Atorvastatin Mylan
Daily 20mg atorvastatin.
PlaceboDrug
Daily Placebo in combination with ICI-therapy
| Study group | Role | What they receive |
|---|---|---|
| Intervention/ Atorvastatin arm | Experimental | Patient will receive 20mg of atorvastatin daily together with ICI-therapy Receives: Drug: Atorvastatin |
| Placebo arm | Placebo comparator | Patient will receive placebo daily together with ICI-therapy Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentual annual growth of atherosclerotic plaques in the descending thoracic aorta
The percentage difference in atherosclerotic plaque volume in the descending part of the thoracic after 1 year of ICI-therapy will be compared to the atherosclerotic plaque volume at baseline.
Measured: 1 year
Secondary outcomes (7)
Difference in percentage increase in non-calcified and calcified atherosclerotic plaque volume in the descending thoracic aorta
Difference in percentage increase in non-calcified and calcified atherosclerotic plaque volume in the descending thoracic aorta 1 year after the start of ICI therapy in the intervention versus the control group
Measured: 1 year
Difference in percentage increase in total, non-calcified and calcified coronary artery atherosclerotic plaque volume
Difference in percentage increase in total, non-calcified and calcified coronary artery atherosclerotic plaque volume
Measured: 1 year
Difference in increase in coronary calcification score (Agatston score) and Multi-Ethnic Study of Atherosclerosis (MESA) score
Difference in increase in coronary calcification score (Agatston score) and MESA score. MESA score calculates the 10-year risk in percentage of developing coronary heart disease.
Measured: 1 year
Difference in change in epicardial fat volume
Difference in change in epicardial fat volume
Measured: 1 year
Difference in reactive hyperaemia in-dex
Difference in reactive hyperaemia in-dex as a marker of endothelial dysfunc-tion using peripheral arterial tonometry (EndoPAT) between intervention and control group.
Measured: 1 year
Difference in Quality of Life between intervention and control group using the FACT-M and EQ5D5L questionnaire.
Difference in QoL between intervention and control group using the FACT-M and the EQ5D5L questionnaires
Measured: Baseline, 3 months, 6 months and 1 year after the start of ICI therapy
Differences in the number of adverse events
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.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jan 2025
- Study startFeb 2025 (estimated)
- Primary completionFeb 2027 (estimated)
- Study completionFeb 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AtherosclerosisStudies of the same condition, open and under way.
- More trials run by Erasmus Medical CenterThe sponsor's other registered studies.
- 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 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 140 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Erasmus Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Amphia Hospital
- Responsible party
- Principal investigator, Jorie Versmissen, Erasmus Medical Center
- Investigators
- Jorie Versmissen, MD,PhD, Principal investigator, Department Internal Medicine, Hospital Pharmacy, Erasmus MC Rotterdam
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06785974
- Sponsor's protocol ID
- 11670
- Acronym
- SPIRAL
- Status last verified
- Dec 2024
- First submitted
- 16 Dec 2024
- Last updated
- 22 Jan 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The data will only become available after the study has been completed for at least 1 year. Only the IPD that have given informed consent to use the anonymous data will be available. After completion of the study, the Erasmus MC policy for requesting data will be applied. Furthermore, the General Data Protection Regulation must be complied with at all times.
Study at a glance
From the registry record, last updated by the sponsor on 22 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Statins to Prevent Immune Checkpoint Inhibitor-induced PRogression of AtherosLerosis
- ClinicalTrials.gov ID
- NCT06785974
- Acronym / sponsor ID
- SPIRAL / 11670
- Conditions
- Atherosclerosis, Melanoma, Immune-related Adverse Event
- Keywords
- Statin, Immune Checkpoint Inhibitor
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 140 participants (estimated)
- Lead sponsor
- Erasmus Medical CenterUniversity, hospital or other
- Collaborators
- Amphia Hospital
- Study start
- Feb 2025 (estimated)
- Primary completion
- Feb 2027 (estimated)
- Study completion
- Feb 2030 (estimated)
- First posted
- 22 Jan 2025 (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 interventional study is to test whether atorvastatin prevents accelerated progression of atherosclerosis in melanoma patients who receive immune checkpoint inhibitor (ICI) therapy. The main questions it aims to answer are:
- difference in percentage growth of total atherosclerotic plaque volume (+ calcified and non-calcified plaque volume) in the descending thoracic segment of the aorta
- difference in percentage growth of total atherosclerotic plaque volume (+ calcified and non-calcified plaque volume) in coronary arteries.
Researchers will compare patients that receive ICI-therapy and atorvastatin with patients that receive ICI-therapy + placebo to see if atorvastatin will prevent accelerated ICI induced plaque growth.
Detailed description
Rationale: Immune checkpoint inhibitors (ICIs) are often highly effective anti-cancer therapies but predispose patients receiving this treatment to cardiovascular disease and thrombotic events. One of the mechanisms by which ICIs increase cardiovascular risk is by stimulation of inflammation and atherosclerosis. Statins (e.g., atorvastatin) are frequently prescribed and effective anti-atherogenic agents, which could provide protective effects on the cardiovascular system in this patient population whilst and after receiving ICI, minimizing cardiovascular sequelae.
The objective of this study is to study if addition of atorvastatin prevents accelerated progression of atherosclerosis during ICI therapy. In addition, the investigators would like to study the effects of atorvastatin during ICI therapy on endothelial function, epicardial fat volume, and hemostatic and inflammatory parameters.
The main study endpoint is the difference in percentage growth of total atherosclerotic plaque volume in the descending thoracic segment of the aorta between intervention and control group, expressed in indexed percentage growth /year.
Secondary endpoints are differences in non-calcified and calcified plaque volume in the thoracic arteries and coronary arteries, epicardial fat volume, endothelial function, and quality of life. Exploratory endpoints include effect on hemostatic and inflammation markers, lipid levels, progression free survival, event free survival, and overall survival.
Trial design Placebo controlled prospective randomised controlled trial.
Trial population Melanoma patients who are scheduled to receive ICI therapy (nivolumab, pembrolizumab, or a combination of anti-PD1/ipilimumab; (neo)adjuvant, irresectable or metastasized melanoma) according to standard-of-care who are also eligible to initiate statin therapy.
The intervention group receives atorvastatin 20mg daily together with ICI therapy. The control group receives placebo together with ICI therapy.
Both groups will undergo two coronary and thoracic CT-scans. In addition, blood withdrawal will take place fourthly during the study. Furthermore, endothelial function will be assessed by means of the EndoPAT device at baseline and after one year of follow-up.
Ethical considerations relating to the clinical trial including the expected benefit to the individual subject or group of patients represented by the trial subjects as well as the nature and extent of burden and risks: Patients in the intervention group will receive atorvastatin, of which safety and tolerability will be carefully monitored. Coronary atherosclerosis will be assessed via two coronary CT-scans, yielding a total limited extra radiation exposure of 4-10mSv. Blood withdrawal will be combined with regular blood withdrawal time points for standard care or will be withdrawn from the intravenous catheter for ICI administration. Vascular endothelial dysfunction will be assessed via Endothelial Peripheral Arterial Tonometry (EndoPAT) by recording finger arterial pulsatile volume change. This non-invasive method forms a minimal extra burden for participating patients. The investigators hypothesize that atorvastatin prevents accelerated progression of atherosclerosis and ameliorates ICI-induced vascular endothelial dysfunction.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intervention/ Atorvastatin arm | Experimental | Drug: AtorvastatinPatient will receive 20mg of atorvastatin daily together with ICI-therapy |
| Placebo arm | Placebo comparator | Drug: PlaceboPatient will receive placebo daily together with ICI-therapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- In order to be eligible to participate in this study, a subject must meet all of the following criteria:
- Age ≥ 18 years
- Able to understand the written information and able to give informed consent
- Melanoma diagnosis with planned ICI treatment according to standard of care (nivolumab, pembrolizumab, monotherapy or combination therapy with ipilimumab)
- Presence of atherosclerosis in the descending thoracic aorta at baseline.
Key exclusion criteria (13 listed)
- Pregnancy or lactation
- Baseline statin use or previously reported statin intolerance
- Current or recent (≤1 year) history of alcohol or drug abuse
- Contra-indication for statin therapy, including:
- Use of essential medication with (potential) interactions with atorvastatin, including:
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 |
|---|---|---|
| AtorvastatinAlso: Lipitor, Atorvastatin MylanDaily 20mg atorvastatin. | Drug | Intervention/ Atorvastatin arm |
| PlaceboDaily Placebo in combination with ICI-therapy | Drug | Placebo arm |
Primary outcome
Percentual annual growth of atherosclerotic plaques in the descending thoracic aorta
Time frame: 1 year
The percentage difference in atherosclerotic plaque volume in the descending part of the thoracic after 1 year of ICI-therapy will be compared to the atherosclerotic plaque volume at baseline.
7 secondary outcomes
Difference in percentage increase in non-calcified and calcified atherosclerotic plaque volume in the descending thoracic aorta
Time frame: 1 year
Difference in percentage increase in total, non-calcified and calcified coronary artery atherosclerotic plaque volume
Time frame: 1 year
Difference in increase in coronary calcification score (Agatston score) and Multi-Ethnic Study of Atherosclerosis (MESA) score
Time frame: 1 year
Difference in change in epicardial fat volume
Time frame: 1 year
Difference in reactive hyperaemia in-dex
Time frame: 1 year
Difference in Quality of Life between intervention and control group using the FACT-M and EQ5D5L questionnaire.
Time frame: Baseline, 3 months, 6 months and 1 year after the start of ICI therapy
Differences in the number of adverse events
Time frame: 1 year
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jan 2025.
- Maarten van der Weijden FoundationLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. The data will only become available after the study has been completed for at least 1 year. Only the IPD that have given informed consent to use the anonymous data will be available. After completion of the study, the Erasmus MC policy for requesting data will be applied. Furthermore, the General Data Protection Regulation must be complied with at all times.
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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.
Jorie Versmissen, MD,PhD principal investigator
Department Internal Medicine, Hospital Pharmacy, Erasmus MC Rotterdam
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Atorvastatin in people with Atherosclerosis and Melanoma, run by Erasmus Medical Center at 1 site in Netherlands.
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 5 inclusion and 13 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: opening soon, as of the sponsor's last update on 22 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 1 site in Netherlands. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Tom Uyl, MD (010-7033202, t.uyl@erasmusmc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentual annual growth of atherosclerotic plaques in the descending thoracic aorta (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 22 Jan 2025.