Rosuvastatin Effect on Atherosclerotic Plaque Metabolism

NCT03233243 | Completed Phase 4

• 1 other identifier: ICNAS-2016-01
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Atherosclerotic plaque uptake of 18F-sodium fluoride (NaF) in positron emission tomography with computed tomography (PET-CT) was recently shown to correlate with clinical instability in patients with CV disease. We hypothesize that rosuvastatin reduces 18F-NaF plaque uptake. Our group will scan coronary, aortic and carotid arteries of high-risk CV subjects with 18F- NaF-PET-CT. Individuals with 18F-NaF-positive plaques will be treated with rosuvastatin for six months, followed by 18F-NaF-PET-CT re-evaluation.

Conditions

Cardiovascular Diseases; Atherosclerosis; Molecular Imaging

Keywords

Rosuvastatin; Sodium fluoride; Positron-emission tomography

Outcome Measures

Primary Outcomes (1)

• Variation in 18F-NaF uptake in coronary, aortic and carotid plaques (tissue to background ratio - TBR)

  * Whole body 18F-NaF-PET-CT for identification of coronary, carotid, thoracic and abdominal aorta arteries plaques: * administration of 125 MBq 18F-NaF intravenously, followed by an attenuation correction CT scan and PET imaging after 60 min. Coronary images will be reconstructed according with the usual protocol of PET-CT. Two-dimensional regions of interest will be drawn around all major epicardial coronary vessels and around the major vessels on three millimetres axial slices. * Quantification of 18F-NaF uptake at baseline and after optimal treatment including statins: * ratio of the maximum standard uptake value (SUV) in the region of interest (the decay corrected tissue concentration of the tracer divided by the injected dose per bodyweight) and blood pool activity in the superior vena cava: tissue-to-background ratio (TBR). * Primary outcome: variation in maximum TBR at any vascular territory (coronary, carotid or aortic)

  6 months

Secondary Outcomes (1)

• Variation in 18F-NaF uptake in coronary, aortic and carotid plaques (corrected uptake per lesion - CUL)

  6 months

Other Outcomes (1)

• Safety outcome

  6 months

Study Arms (2)

Patients with positive 18F-NaF plaques

EXPERIMENTAL

Patients with 18F-NaF-positive plaques (coronary, aortic or carotid) with TBR \> 1.5

Drug: Rosuvastatin Oral Tablet

Patients without 18F-NaF-positive plaques

NO INTERVENTION

Subjects without 18F-NaF- positive plaques will be excluded from the pharmacological intervention study

Interventions

Rosuvastatin Oral Tablet DRUG

Patients with 18F-NaF-positive plaques will be treated with 20 mg of rosuvastatin daily for six months, except in patients who need a 55% LDL reduction to achieve recommended targets (rosuvastatin 40 mg). A second visit (visit 2) will take place eight weeks after therapy initiation to monitor for compliance and adverse events report: therapy will be discontinued if there is an elevation of creatine kinase over five times the ULN with myalgia or alanine amino-transferase three times the ULN.

Patients with positive 18F-NaF plaques

Eligibility Criteria

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

You may qualify if:

• Older than 40 years;
• Written informed consent;
• Considered to be at high or very high CV risk according to the European Society of Cardiology guidelines, fulfilling any of the following criteria:
• predicted fatal CV event at 10 years ≥5% (SCORE tables for low-risk countries);
• chronic kidney disease with glomerular filtration rate (GFR) under 60 mL/min (Modification of Diet in Renal Disease equation - MDRD);
• diabetes mellitus (type 1 or 2);
• markedly elevated single risk factors.

You may not qualify if:

• Previous CV events;
• GFR under 30 mL/min;
• Known hepatic dysfunction or alanine amino-transferase level more than twice the upper limit of the normal (ULN) range;
• Creatine kinase level more than three times the ULN;
• Known myopathy;
• Statin hypersensivity;
• Hormone replacement therapy;
• Malignant neoplasms in the past five years (excluding basal-cell skin carcinoma);
• Uncontrolled hypothyroidism;
• Chronic inflammatory disease (such as rheumatoid arthritis, inflammatory bowel disease);
• Pregnancy or women in child bearing age without contraceptive;

Sponsors & Collaborators

• University of Coimbra: lead
• AstraZeneca: collaborator

Study Sites (1)

Centro Hospitalar e Universitário de Coimbra

Coimbra, 3000-075, Portugal

Location

Related Publications (5)

• Dweck MR, Chow MW, Joshi NV, Williams MC, Jones C, Fletcher AM, Richardson H, White A, McKillop G, van Beek EJ, Boon NA, Rudd JH, Newby DE. Coronary arterial 18F-sodium fluoride uptake: a novel marker of plaque biology. J Am Coll Cardiol. 2012 Apr 24;59(17):1539-48. doi: 10.1016/j.jacc.2011.12.037.

  PMID: 22516444 BACKGROUND

• Joshi NV, Vesey AT, Williams MC, Shah AS, Calvert PA, Craighead FH, Yeoh SE, Wallace W, Salter D, Fletcher AM, van Beek EJ, Flapan AD, Uren NG, Behan MW, Cruden NL, Mills NL, Fox KA, Rudd JH, Dweck MR, Newby DE. 18F-fluoride positron emission tomography for identification of ruptured and high-risk coronary atherosclerotic plaques: a prospective clinical trial. Lancet. 2014 Feb 22;383(9918):705-13. doi: 10.1016/S0140-6736(13)61754-7. Epub 2013 Nov 11.

  PMID: 24224999 BACKGROUND

• Blomberg BA, Thomassen A, de Jong PA, Simonsen JA, Lam MG, Nielsen AL, Mickley H, Mali WP, Alavi A, Hoilund-Carlsen PF. Impact of Personal Characteristics and Technical Factors on Quantification of Sodium 18F-Fluoride Uptake in Human Arteries: Prospective Evaluation of Healthy Subjects. J Nucl Med. 2015 Oct;56(10):1534-40. doi: 10.2967/jnumed.115.159798. Epub 2015 Jul 23.

  PMID: 26205304 BACKGROUND

• Oliveira-Santos M, Castelo-Branco M, Silva R, Gomes A, Chichorro N, Abrunhosa A, Donato P, Pedroso de Lima J, Pego M, Goncalves L, Ferreira MJ. Atherosclerotic plaque metabolism in high cardiovascular risk subjects - A subclinical atherosclerosis imaging study with 18F-NaF PET-CT. Atherosclerosis. 2017 May;260:41-46. doi: 10.1016/j.atherosclerosis.2017.03.014. Epub 2017 Mar 10.

  PMID: 28349887 BACKGROUND

• Ferreira MJV, Oliveira-Santos M, Silva R, Gomes A, Ferreira N, Abrunhosa A, Lima J, Pego M, Goncalves L, Castelo-Branco M. Assessment of atherosclerotic plaque calcification using F18-NaF PET-CT. J Nucl Cardiol. 2018 Oct;25(5):1733-1741. doi: 10.1007/s12350-016-0776-9. Epub 2017 Jan 9.

  PMID: 28070735 BACKGROUND

MeSH Terms

Conditions

Cardiovascular Diseases; Atherosclerosis

Interventions

Rosuvastatin Calcium

Condition Hierarchy (Ancestors)

Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Miguel Castelo-Branco, PhD

  Coimbra's University - Faculty of Medicine

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: DOUBLE
• Who Masked: CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: July 25, 2017
• First Posted: July 28, 2017
• Study Start: July 27, 2020
• Primary Completion: June 20, 2022
• Study Completion: October 27, 2022
• Last Updated: October 28, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

PT (1)