Changes in Plaque Characteristics After Short-term Statin Therapy as Assessed With Coronary CT

NCT ID: NCT06603363

Last Updated: 2025-09-04

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 140 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-05-28
• Study Completion Date: 2028-12-15

Brief Summary

INTENSE Trial is a prospective, double-blind, randomized, placebo-controlled, single-center study with two arms (40 mg intensified statin therapy vs matching placebo for rosuvastatin) among statin-naive patients referred to coronary CT angiography due to stable chest pain, followed for 24 months by using a photon-counting detector CT (PCD-CT).

INTENSE Trial aims 1) to assess the effect of short-term intensified statin therapy on coronary anatomy and physiology using PCD-CT and 2) to determine the impact of short-term, intensified statin therapy on coronary plaque morphology and hemodynamics to identify statin responder and non-responder patients in addition to testing the hypothesis of "plaque memory" after the 24-month follow-up period.

Detailed Description

The extent to which short-term intensified statin treatment may modulate plaque lipid content, alter plaque structure, and change flow physiology as assessed by non-invasive imaging remains unknown. Furthermore, no data is available regarding the effects of short-term intensified statin therapy on coronary plaques as assessed by Photon-Counting Detector CT (PCD-CT). In addition, no data is available regarding the long-term effects of short, intensified statin therapy on plaque morphology (i.e., plaque memory). Therefore, in this randomized, controlled, prospective, double-blind, single-center clinical trial, we aimed 1) to assess the effect of short-term intensified statin therapy on coronary anatomy and physiology using PCD-CT and 2) to assess the effect of short, intensified statin treatment on long term changes in plaque characteristics. In other words, to test our "plaque memory" hypothesis. Our analyses include a detailed evaluation of plaques by combining anatomic (quantitative and qualitative plaque assessment, radiomics) and hemodynamic (Fractional Flow Reserve-CT, FFR-CT) information.

In this randomized, controlled, prospective double-blinded single-center clinical trial, we aim to enroll statin naive patients (patients with no previous or current statin treatment) who underwent PCD-CT (NAEOTOM Alpha, Siemens Healthineers, Erlangen, Germany) exam due to stable chest pain and suspected coronary artery disease (CAD) at the Medical Imaging Centre of Semmelweis University, Budapest, Hungary. Coronary CT Angiography (Coronary CTA) examinations will be performed in accordance with the current guidelines of the Society of Cardiovascular Computed Tomography.

We will enroll patients aged 30-65 years, with at least one partially calcified or non-calcified plaque and with negative FFR-CT (FFR-CT>0.75 distal to stenosis).

Patients with contraindications to coronary CTA and patients post-revascularisation will be excluded from the study. Additional exclusion criteria: patients receiving lipid-lowering therapy before coronary CTA exam; alanine aminotransferase (ALT) levels >3× upper limit of normal (ULN); unexplained serum creatine kinase (CK) level >3× ULN; serum creatinine >2 mg/dL (177 umol/l), elevated low-density lipoprotein (LDL) level >5 mmol/L.

Patients will be randomized into 'high-dose statin' and 'placebo' groups, considering the age and sex of the patients to achieve equal representation of age groups and genders in both arms. Based on the sample size calculation, 70-70 patients must be randomized into each group. For those who will be randomized to the 'high-dose statin' group, 40 mg rosuvastatin therapy will be initiated. For those who will be randomized to the 'placebo' group, a placebo therapy will be started with medications that look the same as 40 mg rosuvastatin pills.

All the included patients will undergo repeated coronary CTA at 3 months and 24 months after the baseline CT. After the 3-month coronary CTA control, rosuvastatin dose per standard of care will be initiated. The 3-month and 24-month control coronary CTA evaluations will be the same as the baseline CT scans. All coronary CTA exams will be performed using a low radiation dose protocol utilizing the advanced imaging capabilities of PCD-CT.

All the included patients will undergo repeated coronary CTA at 3 months and 24 months after the baseline CT with a standardized acquisition protocol.

Proposed scan parameters for all patients are as follows: tube voltage = 120 kVp (due to improved spectral data), automatic tube current modulation with image quality level (IQ-level) = 80, detector configuration = 144 mm × 0.4 mm, rotation time = 0.25 s. All coronary CTA exams will be performed by using a low radiation dose protocol utilizing the advanced imaging capabilities of PCD-CT.

Patients may receive intravenous or oral beta blockers if their heart rate (HR) is > 65 beats/minute before the examination. All patients will receive a nitroglycerine transdermal patch before CTA scanning if systolic blood pressure is > 100 Hgmm. Prospectively triggered acquisition mode is preferred in case of regular HR > 70 beats/min, and helical scan mode if HR is irregular. Images will be acquired in diastole (65-85% of the R-R interval) or systole (200-400 ms), depending on the HR (< or > 75 beats/minute). A four-phasic contrast injection protocol with 70-80 mL contrast agent at a flow rate of 4.5-5.0 mL/s is recommended.

Special attention will be given to ensure that the baseline CT scan parameters are consistent with the follow-up scans for each patient. Images and coronary segments with severe motion, breathing, beam-hardening, or misalignment artifacts will be excluded from the analysis. Coronary segments matched to the segment with artifacts will also be excluded in all scans.

The primary endpoint will be evaluated at 3 months, while "plaque memory" will be assessed at 24 months of follow-up.

Conditions

Coronary Artery Disease; Atherosclerotic Plaque; Coronary Computed Tomography Angiography; Statin Therapy; Multidetector Computed Tomography; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Vascular Diseases; Hyperlipidemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Intensified Statin Arm

Participants will receive one capsule (40 mg of rosuvastatin), taken once daily for 3 months, orally with or without food. After the 3-month visit, the dose will be reduced to a dose per standard of care.

Group Type: EXPERIMENTAL

Rosuvastatin 40mg

Intervention Type: DRUG

Participants will receive 40 mg of rosuvastatin once a day for 3 months. After the 3-month visit, the dose will be reduced to a dose per standard of care.

Coronary Computed Tomography Angiography (Coronary CTA)

Intervention Type: DIAGNOSTIC_TEST

Computed Tomography Angiography including coronary calcium scoring and coronary computed tomography angiography at baseline, 3-month, and 24-month visits with a PCD-CT scanner.

Blood test

Intervention Type: DIAGNOSTIC_TEST

Blood test at baseline, 3-month, and 24-month visits.

Placebo Arm

Participants will receive one capsule (a placebo for rosuvastatin), taken once daily for 3 months, orally with or without food. After the 3-month visit standard rosuvastatin therapy will be initiated.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Participants will receive a placebo for rosuvastatin once a day for 3 months. After the 3-month visit, standard rosuvastatin will be initiated.

Coronary Computed Tomography Angiography (Coronary CTA)

Intervention Type: DIAGNOSTIC_TEST

Computed Tomography Angiography including coronary calcium scoring and coronary computed tomography angiography at baseline, 3-month, and 24-month visits with a PCD-CT scanner.

Blood test

Intervention Type: DIAGNOSTIC_TEST

Blood test at baseline, 3-month, and 24-month visits.

Interventions

Rosuvastatin 40mg

Participants will receive 40 mg of rosuvastatin once a day for 3 months. After the 3-month visit, the dose will be reduced to a dose per standard of care.

Intervention Type: DRUG

Placebo

Participants will receive a placebo for rosuvastatin once a day for 3 months. After the 3-month visit, standard rosuvastatin will be initiated.

Intervention Type: DRUG

Coronary Computed Tomography Angiography (Coronary CTA)

Computed Tomography Angiography including coronary calcium scoring and coronary computed tomography angiography at baseline, 3-month, and 24-month visits with a PCD-CT scanner.

Intervention Type: DIAGNOSTIC_TEST

Blood test

Blood test at baseline, 3-month, and 24-month visits.

Intervention Type: DIAGNOSTIC_TEST

Other Intervention Names

Intensified Statin Therapy; Coronary CTA; Laboratory test

Eligibility Criteria

Inclusion Criteria

• patients referred for coronary computed tomography angiography (CTA)
• females aged 45-75 years and males aged 40-75 years
• presence of at least mild coronary atherosclerosis (luminal stenosis >25%, with at least one partially calcified or non-calcified plaque)
• statin-naive patients
• ability to understand and provide written informed consent
• FFR-CT value ≥0.75, indicating the absence of hemodynamically significant stenosis

Exclusion Criteria

• contraindications to coronary CTA
• current or prior treatment with statins or other lipid-lowering agents (e.g., ezetimibe)
• age below 45 years in females or below 40 years in males
• age above 75 years in both sexes
• pregnancy or breastfeeding
• type 1 or type 2 diabetes mellitus
• history of coronary stent implantation or coronary artery bypass grafting
• history of myocardial infarction
• ≥70% luminal stenosis in the proximal left anterior descending artery (LAD), or ≥50% stenosis in the left main (LM) coronary artery
• FFR-CT value <0.75 in any coronary artery
• elevated serum alanine aminotransferase (ALT) levels (>3× the upper limit of normal)
• elevated serum creatine kinase (CK) levels (>3× the upper limit of normal)
• LDL cholesterol level >5 mmol/L
• renal failure or significantly impaired renal function (eGFR <30 mL/min/1.73 m²)
• ongoing oncological treatment
• active liver disease
• known hypersensitivity to any excipients of the investigational product
• concomitant treatment with the combination of sofosbuvir/velpatasvir/voxilaprevir
• concomitant treatment with cyclosporine
• women of childbearing potential not using adequate contraception
• presence of myopathy

• Minimum Eligible Age: 45 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Research, Development and Innovation Office, Hungary

UNKNOWN

Sponsor Role: collaborator

HeartFlow, Inc.

INDUSTRY

Sponsor Role: collaborator

Prof. Maurovich-Horvat Pál

OTHER

Sponsor Role: lead

Responsible Party

Prof. Maurovich-Horvat Pál

Head of Clinic for Medical Imaging

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Pál Maurovich-Horvat, Prof., Dr.

Role: PRINCIPAL_INVESTIGATOR

Medical Imaging Centre, Budapest, Hungary

Marc Dewey, Prof., Dr.

Role: STUDY_CHAIR

Charite University, Berlin, Germany

Béla Merkely, Prof., Dr.

Role: STUDY_CHAIR

Heart and Vascular Centre, Budapest, Hungary

Locations

Semmelweis University, Medical Imaging Centre

Budapest, Budapest, Hungary

Site Status: RECRUITING

Countries

Hungary

Central Contacts

Pál Maurovich-Horvat, Prof., Dr.

Role: CONTACT

maurovich-horvat.pal@semmelweis.hu

+36206632485

Facility Contacts

Pál Maurovich-Horvat, MD, PhD, DSc

Role: primary

maurovich-horvat.pal@semmelweis.hu

+36206632485

Other Identifiers

2025-521367-12-00

Identifier Type: CTIS

Identifier Source: secondary_id

BM/17433-1/2024

Identifier Type: -

Identifier Source: org_study_id