Clinical trial NCT06603363: Changes in Plaque Characteristics After Short-term Statin Therapy As Assessed with Coronary CT
Official title: Changes in Plaque Characteristics After Short-term Statin Therapy As Assessed with Coronary CT
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Coronary Artery Disease
Atherosclerotic Plaque
Coronary Computed Tomography Angiography
Statin Therapy
Multidetector Computed Tomography
Heart Diseases
Cardiovascular Diseases
Arteriosclerosis
Vascular Diseases
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
Lead sponsor: Semmelweis University
Sponsor class: OTHER
Collaborators: name: National Research, Development and Innovation Office, Hungary
First posted: 2024-09-19
Enrollment: 140
Sex: ALL
Minimum age (years): 30
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: Inclusion Criteria:

* Clinically indicated coronary CT angiography
* Min. 35 yo. females or min. 30 yo. males
* Statin naive patients
* There are no contraindications to CT angiography
* Understanding and signing the consent form
* At least one partially-calcified or non-calcified plaque
* FFRCT\>0.75 distal to stenosis

Exclusion Criteria:

* History of statin treatment
* \<35 yo. females or \<30 yo. males
* Diabetes mellitus (Type I. and II.)
* Coronary artery stent or bypass graft
* Previous myocardial infarction
* Elevated alanine aminotransferase levels (\>3x upper limit of normal)
* Elevated creatine kinase (\>3x upper limit of normal)
* Elevated low density lipoprotein (\>5 mmol/L)
* Pregnancy or breastfeeding
* Chronic renal failure (eGFR \<30 ml/m2)
* Active oncological treatment
* ≥70% luminal stenosis in proximal LAD or ≥50% luminal stenosis in left main coronary artery

Primary outcomes:
measure: Change in non-calcified plaque volume during a 3-month follow-up period.
timeFrame: 12 weeks
measure: Change in total plaque volume at 3-month follow-up period.
timeFrame: 12 weeks
Secondary outcomes:
measure: Change in low attenuation non-calcified plaque volume during a 3-month follow-up period.
timeFrame: 12 weeks
measure: Change in low attenuation non-calcified plaque volume during a 24-month follow-up period.
timeFrame: 24 months
measure: Change in total plaque volume during a 24-month follow-up period.
timeFrame: 24 months
measure: Change in total plaque volume between 3- and 24-month follow-up period.
timeFrame: 21 months
measure: Total plaque volume at 3-month follow-up period.
timeFrame: 12 weeks
measure: Total plaque volume at 24-month follow-up period.
timeFrame: 24 months
measure: Change in non-calcified plaque volume between 3- and 24-month follow-up period.
timeFrame: 21 months
measure: Change in non-calcified plaque volume during a 24-month follow-up period.
timeFrame: 24 months
measure: Change in plaque composition during a 3-month follow-up period.
timeFrame: 12 weeks
measure: Change in plaque composition during a 24-month follow-up period.
timeFrame: 24 months
measure: Change in per-vessel fractional flow reserve [FFRCT] during a 3-month follow-up period.
timeFrame: 12 weeks
measure: Change in per-vessel fractional flow reserve [FFRCT] during a 24-month follow-up period.
timeFrame: 24 months
measure: Change in the prevalence of high-risk plaque features during a 3-month follow-up period.
timeFrame: 12 weeks
measure: Change in the prevalence of high-risk plaque features during a 24-month follow-up period.
timeFrame: 24 months
measure: Change in radiomic features during a 24-month follow-up period.
timeFrame: 24 months
measure: Change in radiomic features during a 3-month follow-up period.
timeFrame: 12 weeks
measure: Prevalence of major adverse cardiac event
timeFrame: From inclusion up to a maximum follow-up period of 4 years
measure: Prevalence of clinical adverse event
timeFrame: From inclusion up to a maximum follow-up period of 4 years
Other outcomes:
measure: Changes in blood lipid profile
timeFrame: Measured at baseline, at 3-month and 24-month
measure: Changes in inflammatory markers
timeFrame: Measured at baseline, at 3-month and 24-month
measure: Changes in markers of glucose homeostasis
timeFrame: Measured at baseline, at 3-month and 24-month
Locations:
city: Budapest
country: Hungary
facility: Semmelweis University, Medical Imaging Centre
Study officials:
affiliation: Medical Imaging Centre, Budapest, Hungary
name: Pál Maurovich-Horvat, Prof., Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: Charite University, Berlin, Germany
name: Marc Dewey, Prof., Dr.
role: STUDY_CHAIR
affiliation: Heart and Vascular Centre, Budapest, Hungary
name: Béla Merkely, Prof., Dr.
role: STUDY_CHAIR
References: