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Virtual Histology Findings and Effects of Varying Doses of Atorvastatin Treatment (VENUS)

This study has been completed.
Sponsor:
Collaborators:
Queen Mary Hospital, Hong Kong
Pfizer
Information provided by (Responsible Party):
Prof. Stephen Lee, The University of Hong Kong
ClinicalTrials.gov Identifier:
NCT01200056
First received: September 9, 2010
Last updated: February 27, 2013
Last verified: February 2013
  Purpose

While statin treatment may induce plaque regression, the effect of statin on plaque composition with varying doses is unknown. This study assessed such effects by volumetric virtual histology intravascular ultrasound (VH-IVUS).

In this prospective, randomized, double-blinded pilot study, statin-naïve patients with stable angina requiring percutaneous coronary intervention (PCI) were randomized to receive 6 months of either atorvastatin 10mg or 40 mg daily. VH-IVUS was performed in all non-PCI lesions at baseline and 6 months; all analyses were performed by core laboratory.


Condition Intervention Phase
Coronary Disease
Ultrasonography, Interventional
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Drug: Atorvastatin 10mg versus 40mg.
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Prospective, Double-blinded, Randomised Study to Evaluate the Effects of Different Doses of Statin Treatment on Plaque Volume and Composition in Coronary Disease Determined by Virtual Histology Using Intravascular Ultrasound

Resource links provided by NLM:


Further study details as provided by The University of Hong Kong:

Primary Outcome Measures:
  • The primary endpoint would be the 6-month angiographic and VH-IVUS restudy findings. [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Our hypothesis was plaque regression and virtual histology intravascular ultrasound (VH-IVUS) plaque modification with statin therapy could be statin dose dependent, and may affect clinical outcomes. 2 clinically realistic doses of atorvastatin 10mg and 40mg were chosen in statin-naïve patients without previous myocardial infarction. The primary endpoint of this study would therefore be the 6 months angiographic and IVUS follow-up, looking at the volumetric gray-scale IVUS and VH-IVUS findings at 6 months for the whole cohort as well as the differences between the 2 groups.


Secondary Outcome Measures:
  • The secondary endpoint would be the occurrence of any major adverse cardiac events at 6 months (including any death, myocardial infarction or need for revascularization) as routinely monitored after all percutaneous interventional procedures. [ Time Frame: Throughout the 6 months study period. ] [ Designated as safety issue: No ]
    As described in the "Title" above.


Enrollment: 40
Study Start Date: August 2007
Study Completion Date: June 2010
Primary Completion Date: November 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Atorvastatin 10mg low dose
Atorvastatin 10mg daily for 6 months and compared to atorvastatin 40mg daily in the other arm. The primary endpoint of 6 months VH-IVUS findings and clinical outcomes would be monitored and compared.
Drug: Atorvastatin 10mg versus 40mg.
2 arms comparing atorvastatin 10mg daily for 6 months to atorvastatin 40mg daily for 6 months. The primary endpoint would be the 6 months VH-IVUS findings and clinical outcomes.
Other Name: Lipitor 10mg versus 40mg daily for 6 months.
Active Comparator: Atorvastatin 40mg moderate dose
Atorvastatin 40mg daily for 6 months and compared to atorvastatin 10mg daily in the other arm. The primary endpoint of 6 months VH-IVUS findings and clinical outcomes would be monitored and compared.
Drug: Atorvastatin 10mg versus 40mg.
2 arms comparing atorvastatin 10mg daily for 6 months to atorvastatin 40mg daily for 6 months. The primary endpoint would be the 6 months VH-IVUS findings and clinical outcomes.
Other Name: Lipitor 10mg versus 40mg daily for 6 months.

Detailed Description:

Statin therapy, especially at intensive doses, is beneficial in atherosclerotic coronary disease. Detecting subtle plaque regression after statin therapy is difficult by coronary angiogram; intravascular ultrasound (IVUS) is a far better method. Volumetric IVUS has been used in statin trials to evaluate plaque regression. Intensive statin therapy in the REVERSAL Trial and ASTEROID Trial appeared to achieve better regression outcomes. Stable fibrous plaque is likely to be responsible for stable ischemia, while unstable plaque (large lipid core, calcified nodule and necrotic core), thin-cap fibroatheroma, plaque erosion and plaque rupture may be responsible for acute coronary syndrome (ACS). In vivo tissue characterization of plaque composition is therefore important, yet in this regard grayscale IVUS is insufficient. The development of Virtual Histology (VH) utilizing IVUS generated radiofrequency backscattering signals to virtually separate plaque composition into 4 components corresponding to histopathology has made possible in vivo assessment of plaque composition and stability. We believed plaque regression and VH-IVUS plaque modification with statin therapy could be statin dose dependent, and may affect clinical outcomes. This study was designed to prove our hypothesis, utilizing VH-IVUS.

This study is the first prospective, randomised, double-blinded pilot study designed to investigate the varying statin dose effects on plaque regression and VH composition modulation. For ethical reasons, a placebo arm was not designed. Based on available data, clinically realistic doses of atorvastatin 10mg (low dose) and 40mg (moderate dose) were chosen. Only statin-naïve patients without previous history of myocardial infarction (MI) would be selected, aiming to show the "pure" effects of varying doses of statin and to better reveal the subtle differences in the changes.

  Eligibility

Ages Eligible for Study:   18 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patient aged 18 to 85 (not pregnant) requiring percutaneous intervention to coronary stenosis.
  • Statin naive patient.
  • No history of myocardial infarction. Angina free for at least 8 weeks.

Exclusion Criteria:

  • Any history of previous statin treatment and myocardial infarction
  • Current acute coronary syndrome or in cardiogenic shock
  • Surgical bypass candidate
  • Chronic total occlusion and very tortuous calcified arteries precluding safe IVUS examination.
  • Patient refused to give written informed consent.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01200056

Locations
China, Hong Kong
Department of Medicine, the University of Hong Kong, Queen Mary Hospital, Hospital Authority
Hong Kong SAR, Hong Kong, China
Sponsors and Collaborators
Prof. Stephen Lee
Queen Mary Hospital, Hong Kong
Pfizer
Investigators
Principal Investigator: Prof. Stephen WL LEE, MD FRCP FACC Department of Medicine, the University of Hong Kong, Queen Mary Hospital, Hospital Authority
  More Information

Publications:

Responsible Party: Prof. Stephen Lee, Professor and Chief, The University of Hong Kong
ClinicalTrials.gov Identifier: NCT01200056     History of Changes
Other Study ID Numbers: UW 07-266 (IRB HKU), HKCTR-517
Study First Received: September 9, 2010
Last Updated: February 27, 2013
Health Authority: Hong Kong: Ethics Committee

Keywords provided by The University of Hong Kong:
Volumetric virtual histology intravascular ultrasound.
Statin-naive patient.
Varying doses atorvastatin.
Clinical outcomes.

Additional relevant MeSH terms:
Coronary Artery Disease
Coronary Disease
Arterial Occlusive Diseases
Arteriosclerosis
Cardiovascular Diseases
Heart Diseases
Myocardial Ischemia
Vascular Diseases
Atorvastatin
Anticholesteremic Agents
Antimetabolites
Enzyme Inhibitors
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Hypolipidemic Agents
Lipid Regulating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 27, 2014