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

NCT06603363 | Recruiting DMC

• 2 other identifiers: BM/17433-1/20242025-521367-12-00
• Study Type: interventional
• Target: 140
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

coronary artery disease; stable chest pain; intermediate pretest probability; explanatory randomised controlled trial; coronary computed tomography angiography; photon-counting detector CT; atherosclerotic plaque; statin therapy

Outcome Measures

Primary Outcomes (1)

• Change in non-calcified plaque volume during a 3-month follow-up period.

  Expressed as absolute change and as a percentage of baseline.

  12 weeks

Secondary Outcomes (18)

• Change in total plaque volume at 3-month follow-up period.

  12 weeks

• Change in low attenuation non-calcified plaque volume during a 3-month follow-up period.

  12 weeks

• Change in low attenuation non-calcified plaque volume during a 24-month follow-up period.

  24 months

• Change in total plaque volume during a 24-month follow-up period.

  24 months

• Change in total plaque volume between 3- and 24-month follow-up period.

  21 months

Other Outcomes (3)

• Changes in blood lipid profile

  Measured at baseline, at 3-month and 24-month

• Changes in inflammatory markers

  Measured at baseline, at 3-month and 24-month

• Changes in markers of glucose homeostasis

  Measured at baseline, at 3-month and 24-month

Study Arms (2)

Intensified Statin Arm

EXPERIMENTAL

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.

Drug: Rosuvastatin 40mg; Diagnostic Test: Coronary Computed Tomography Angiography (Coronary CTA); Diagnostic Test: Blood test

Placebo Arm

PLACEBO COMPARATOR

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.

Drug: Placebo; Diagnostic Test: Coronary Computed Tomography Angiography (Coronary CTA); Diagnostic Test: Blood test

Interventions

Rosuvastatin 40mg 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.

Also known as: Intensified Statin Therapy

Intensified Statin Arm

Placebo DRUG

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

Placebo Arm

Blood test DIAGNOSTIC_TEST

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

Also known as: Laboratory test

Intensified Statin Arm; Placebo Arm

Coronary Computed Tomography Angiography (Coronary CTA) 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.

Also known as: Coronary CTA

Intensified Statin Arm; Placebo Arm

Eligibility Criteria

• Age: 45 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Prof. Maurovich-Horvat Pál: lead
• National Research, Development and Innovation Office, Hungary: collaborator
• HeartFlow, Inc.: collaborator

Study Sites (1)

Semmelweis University, Medical Imaging Centre

Budapest, Budapest, 1082, Hungary

RECRUITING

MeSH Terms

Conditions

Coronary Artery Disease; Plaque, Atherosclerotic; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Vascular Diseases; Hyperlipidemias

Interventions

Rosuvastatin Calcium; Hematologic Tests; Clinical Laboratory Techniques

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Arterial Occlusive Diseases; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques

Study Officials

• Pál Maurovich-Horvat, Prof., Dr.

  Medical Imaging Centre, Budapest, Hungary

  PRINCIPAL INVESTIGATOR

• Marc Dewey, Prof., Dr.

  Charite University, Berlin, Germany

  STUDY CHAIR

• Béla Merkely, Prof., Dr.

  Heart and Vascular Centre, Budapest, Hungary

  STUDY CHAIR

Central Study Contacts

Pál Maurovich-Horvat, Prof., Dr.

CONTACT

+36206632485; maurovich-horvat.pal@semmelweis.hu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Head of Clinic for Medical Imaging

Study Record Dates

• First Submitted: September 3, 2024
• First Posted: September 19, 2024
• Study Start: May 28, 2025
• Primary Completion (Estimated): October 15, 2026
• Study Completion (Estimated): December 15, 2028
• Last Updated: May 13, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share
• Time Frame: Clinical and imaging data will be available after the results have been published.
• Access Criteria: Access request needs to be made directly to the PI.

Locations

HU (1)