Virtual Histology Findings and Effects of Varying Doses of Atorvastatin Treatment

Coronary Disease Clinical Trial

— VENUS  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01200056
• Other study ID #: UW 07-266 (IRB HKU)
• Secondary ID: HKCTR-517
• Status: Completed
• Phase: Phase 4
• First received: September 9, 2010
• Last updated: February 27, 2013
• Start date: August 2007
• Est. completion date: June 2010

Study information

• Verified date: February 2013
• Source: The University of Hong Kong
• Contact: n/a
• Is FDA regulated: No
• Health authority: Hong Kong: Ethics Committee
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: June 2010
• Est. primary completion date: November 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 85 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Hydroxymethylglutaryl-CoA Reductase Inhibitors
• Ultrasonography, Interventional

Intervention

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.

Locations

Country	Name	City	State
China	Department of Medicine, the University of Hong Kong, Queen Mary Hospital, Hospital Authority	Hong Kong SAR	Hong Kong

Sponsors (3)

Lead Sponsor	Collaborator
Prof. Stephen Lee	Pfizer, Queen Mary Hospital, Hong Kong

Country where clinical trial is conducted

China, 

References & Publications (31)

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* Note: There are 31 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The primary endpoint would be the 6-month angiographic and VH-IVUS restudy findings.	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.	6 months	No
Secondary	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.	As described in the "Title" above.	Throughout the 6 months study period.	No