Changes in plaque characteristics after short-term statin therapy assessed with coronary CT (INTENSE)

2025-522868-32-00 Protocol INTENSE Phase II and Phase III (Integrated) Authorised, recruitment pending

Status Authorised, recruitment pending · 1 EU/EEA countries · 1 sites · Protocol INTENSE

Overview

Sponsor-declared trial summary

Phase Phase II and Phase III (Integrated)
Status Authorised, recruitment pending
Participants planned 140
Countries 1
Sites 1

Coronary Artery Disease

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

Key facts

Sponsor
Semmelweis University
Participant type
Patients
Age range
18-64 years, 65+ years
Gender
Male and Female
Therapeutic area
Diseases [C] - Cardiovascular Diseases [C14]
Decision date (initial)
2025-09-26
Transition trial
No
Low-intervention
Yes
Rare-disease indication
No
Vulnerable population
No
Funding sources
National Research, Development and Innovation Office – Hungarian Scientific Research Fund

External identifiers

EU CT number
2025-522868-32-00
ClinicalTrials.gov
NCT06603363

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Diagnosis, Therapy, Dose response

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

Secondary objectives 20

  1. Change in total plaque volume at 3-month follow-up period.
  2. Change in total plaque volume during a 24-month follow-up period.
  3. Change in total plaque volume between 3- and 24-month follow-up period.
  4. Change in low attenuation non-calcified plaque volume during a 3-month follow-up period.
  5. Change in low attenuation non-calcified plaque volume during a 24-month follow-up period.
  6. Change in non-calcified plaque volume between 3- and 24-month follow-up period.
  7. Change in non-calcified plaque volume during a 24-month follow-up period.
  8. Change in plaque composition during a 3-month follow-up period.
  9. Change in plaque composition during a 24-month follow-up period.
  10. Change in per-vessel fractional flow reserve [FFRCT] during a 3-month follow-up period.
  11. Change in per-vessel fractional flow reserve [FFRCT] during a 24-month follow-up period.
  12. Change in the prevalence of high-risk plaque features during a 3-month follow-up period.
  13. Change in the prevalence of high-risk plaque features during a 24-month follow-up period.
  14. Change in radiomic features during a 24-month follow-up period.
  15. Change in radiomic features during a 3-month follow-up period.
  16. Prevalence of major adverse cardiac event
  17. Prevalence of clinical adverse event.
  18. Changes in blood lipid profile.
  19. Changes in inflammatory markers.
  20. Changes in markers of glucose homeostasis.

Conditions and MedDRA coding

Coronary Artery Disease

VersionLevelCodeTermSystem organ class
20.0 PT 10058108 Dyslipidaemia 100000004861
27.0 LLT 10090144 Nonobstructive coronary artery disease 100000004849
27.0 LLT 10090447 Coronary artery atherosclerotic heart disease 100000004849
20.0 PT 10011078 Coronary artery disease 100000004849

Study design 5 periods

#TitleAllocationBlindingRoles blindedArms
1 Screening Period
We will enroll statin-naive, consecutive patients referred to clinically indicated coronary CTA due to stable chest pain with at least one partially calcified or non-calcified plaque and with negative FFR-CT. Apart from the baseline CTA, laboratory tests will be performed.
 Not Applicable None
2 Randomization
In case all inclusion criteria are met, and no exclusion criteria are present, patients are 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 sample size calculation 70-70 patients will be needed to get randomized into each group.
 Randomised Controlled Double [{"id":132403,"code":5,"name":"Carer"},{"id":132401,"code":2,"name":"Investigator"},{"id":132402,"code":4,"name":"Analyst"},{"id":132400,"code":1,"name":"Subject"}]
3 Treatment
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. The treatment period will take 3 months.
 Randomised Controlled Double [{"id":132405,"code":1,"name":"Subject"},{"id":132407,"code":4,"name":"Analyst"},{"id":132408,"code":5,"name":"Carer"},{"id":132406,"code":2,"name":"Investigator"}]
4 Short term follow-up
All the included patients will undergo repeated coronary CTA and laboratory tests at 3 months. The 3-month control coronary CTA protocol and evaluations will be the same as the baseline CT scans. After the 3-month coronary CTA control, both groups will receive 20 mg of rosuvastatin statin therapy.
 Not Applicable None
5 Long term follow-up
All the included patients will undergo repeated coronary CTA and laboratory tests at 24 months. The 24-month control coronary CTA protocol and evaluations will be the same as the previous CTA scans.
 Not Applicable None

Regulatory references

Scientific advice from competent authorities
Nemzeti Nepegeszseguegyi Koezpont
Plan to share IPD
Yes
IPD plan description
GUIDE-IT platform (www.guide-it.org) will be used for sharing clinical and imaging data after results are published.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

  1. Clinically indicated coronary CT angiography
  2. 45-75 yo. females or min. 40-75 yo. males
  3. Statin naive patients
  4. There are no contraindications to CT angiography
  5. Understanding and signing the consent form
  6. At least one partially-calcified or non-calcified plaque
  7. FFRCT>0.75 distal to stenosis

Exclusion criteria 19

  1. History of statin or other lipid lowering (ezetimibe) treatment
  2. Elevated alanine aminotransferase levels (>3x upper limit of normal)
  3. Elevated creatine kinase (>3x upper limit of normal)
  4. Elevated low density lipoprotein (>5 mmol/L)
  5. Pregnancy or breastfeeding
  6. >75 yo. patients (both genders)
  7. Chronic renal failure or decreased renal function (eGFR <30 ml/m2)
  8. Active oncological treatment
  9. ≥70% luminal stenosis in proximal LAD or ≥50% luminal stenosis in left main coronary artery
  10. FFRCT<0.75 distal to stenosis
  11. females below 45 yo. or males below 40 yo.
  12. Diabetes mellitus (Type I. and II.)
  13. Coronary artery stent or bypass graft
  14. Previous myocardial infarction
  15. Acute liver disease
  16. Hypersensitivity to any of the excipients of the investigational medicinal product
  17. Concomitant treatment with the sofosbuvir/velpatasvir/voxilaprevir combination.
  18. Concomitant treatment with cyclosporine.
  19. Women of childbearing potential who are not using an adequate method of contraception.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

  1. Non-calcified plaque volume at 3 months follow-up (expressed as mm3).

Secondary endpoints 16

  1. Plaque composition measured during the 3-month visit: each component expressed in mm³ – low attenuation: −100 to 30 HU; non-calcified: 30 to 350 HU; calcified: >350 HU.
  2. Major adverse events (death, cardiovascular death, fatal and nonfatal myocardial infarction, fatal and nonfatal stroke/TIA, unstable angina, hospitalization))
  3. Minor adverse events (muscle pain, constipation, abdominal pain or meteorismus, nausea, headache, vertigo, fatigue, skin rash, pruritus)
  4. Laboratory parameters (total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, LP(a), apoA1, apoB, hs-CRP, ferritin and hemoglobin A1c.
  5. Total plaque volume (mm3) during the 3-month follow up
  6. Low-attenuation non-calcified plaque volume during the 24-month follow-up period (mm³)
  7. CT-based Fractional Flow Reserve (FFR-CT) during the 3 months follow-up
  8. CT-based Fractional Flow Reserve (FFR-CT) during the 24 months follow-up
  9. Plaque composition measured during the 24-month visit: each component expressed in mm³ – low attenuation: −100 to 30 HU; non-calcified: 30 to 350 HU; calcified: >350 HU.
  10. Low-attenuation non-calcified plaque volume during the 3-month follow-up period (expressed in mm³)
  11. Total plaque volume (mm3) during the 24-month follow up
  12. Visual presence of high risk plaque features during the 3-month follow up: low attenuation plaque, positive remodeling, napkin-ring sign, spotty calcification, minimal luminal area or plaque burden ≥70%
  13. Radiomic features during the 3-month follow up
  14. Radiomic features during the 24-month follow-up
  15. Non-calcified plaque volume at 24 months follow-up (expressed as mm3).
  16. Visual presence of high risk plaque features during the 24-month follow up: low attenuation plaque, positive remodeling, napkin-ring sign, spotty calcification, minimal luminal area or plaque burden ≥70%

Investigational products

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

Test 1

Xeter 10 mg filmtabletta

PRD671566 · Product

Active substance
Rosuvastatin
Pharmaceutical form
FILM-COATED TABLET
Route of administration
ORAL
Max daily dose
40 mg milligram(s)
Max total dose
3600 mg milligram(s)
Max treatment duration
12 Week(s)
Authorisation status
Authorised
ATC code
C10AA07 — ROSUVASTATIN
Marketing authorisation
OGYI-T-21173/03
MA holder
GEDEON RICHTER PLC.
MA country
Hungary
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Placebo 1

Tabletta placebo 0,2 g fehér, laktózmentes (4x) tartalmú kapszula

N/A · Product

Other product name
N/A
Pharmaceutical form
N/A
ATC code
N/A — N/A
Marketing authorisation
N/A
MA holder
N/A
MA country
Iceland
Paediatric formulation
No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Semmelweis University

13 Total trials 3 Recruiting 1 Ended
Commercial
Sponsor organisation
Semmelweis University
Address
Ulloi Ut 78/a
City
Budapest
Postcode
1082
Country
Hungary

Scientific contact point

Organisation
Semmelweis University
Contact name
Barnabas Baksa

Public contact point

Organisation
Semmelweis University
Contact name
Barnabas Baksa

Locations

1 EU/EEA country · 1 investigational sites

By country

CountryMS statusPlanned subjectsSites
Hungary Authorised, recruitment pending 140 1
Rest of world — 0 —

Investigational sites

Hungary

1 site · Authorised, recruitment pending
Semmelweis University
Radiology, Koranyi Sandor Utca 2/a, Kerulet, Budapest VIII

Results and documents

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

Documents 7 files

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

TypeTitleVersion
Protocol (for publication) D1_Protocol_HU_2025-521367-12-00 2
Recruitment arrangements (for publication) Betegkartya 1
Recruitment arrangements (for publication) K1_Recruitment_Arrangements_HU_2025-521367-12-00 2
Subject information and informed consent form (for publication) L1_SIS_and_ICF_Adults_HU_2025-521367-12-00 1
Summary of Product Characteristics (SmPC) (for publication) G2_SmPC_Rosuvastatin 1
Synopsis of the protocol (for publication) D1_Protocol_Synopsis_ENG_2025-52-1367-12-00 1
Synopsis of the protocol (for publication) D1_Protocol_Synopsis_HU_2025-52-1367-12-00 1

Application history

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

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2025-06-27 Hungary Acceptable
2025-09-08
 2025-09-26

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