THE ERASE TRIAL
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Objective
To study the effects of reconstituted HDL on atheromatous plaque volume as assessed by intravascular ultrasound (IVUS).
Timeline
Start Date
July 2006
End Date
October 2006
Methods
- Patients Enrolled: 183 patients
- Monitoring of adverse events, physical exam findings, ECG, and lab results were used to assess patient safety. Blood was withdrawn immediately before and 24 hours after infusion. If liver transaminases were > 5 times upper normal limit, patients withdrew blood after 3 days of infusion
Inclusion Criteria
- Age: 30-75 years
- Women with no child bearing potential
- Patients in need for coronary angiography with at least 1 stenosis of 20% or more on baseline coronary angiography.
Exclusion Criteria
- Patients with > 50% stenosis in left main coronary artery
- Renal insufficiency
- Liver or hepatic disease
- Uncontrolled diabetes mellitus
- Symptomatic heart failure of NYHA class III or IV
- Soybean allergy (component of CSL-111 infusion)
- History of alcohol or drug abuse
- Warfarin or heparin anticoagulation during infusion period
Study Arms
- 60 patients receiving placebo, defined as normal saline infusion
- 111 patients receiving CSL-111 infusion at a dose of 40 mg/kg
- 12 patients receiving CSL-111 infusion at a dose of 80 mg/kg
Therapy was required to take place within 2 weeks of an acute coronary syndrome. Before infusion, baseline IVUS of target coronary artery using 40-MHz catheters was performed and need to fulfill the following conditions:
- Proximal 4 cm needed to have a reference diameter of at least 2.5 mm
- No filling defects of thrombotic nature
- No reduced luminal diameter by 50% or more according to angiographic estimation at baseline
- No previous percutaneous coronary intervention (PCI)
- Not a previous candidate for intervention at time of the baseline characteristic.
Patients received 4 weekly volume-matched infusions; but infusions can be postponed for 1 week on a maximum of 2 consecutive occasions if liver transaminases were > 1.5 times the upper normal limit.
Follow-up IVUS at the same target artery segment occurred 2-3 weeks after last infusion:
- 47 patients of placebo group had baseline and follow-up IVUS
- 89 patients of CSL-111 40 mg/kg group had baseline and follow-up IVUS
- 9 patients of CSL-111 80 mg/kg group had baseline and follow-up IVUS
Outcomes
Primary Outcome
Percentage difference in volume of atheroma between follow-up and baseline on IVUS.
Secondary Outcome
Absolute change in coronary score, defined as the mean of minimal lumen diameter for all measured lesions on angiography, and change in plaque volume and characterization on IVUS
Results
After 4 weeks of infusion, plaque volume changes was not significantly different among the placebo and CSL-111 40 mg/kg groups (p=0.48). There was a significant change in atheroma volume in both groups when compared to baseline volume(-1.62% in placebo (p=0.07) and -3.41% in CSL-111 40 mg/kg (p<0.001), but the change was not significant when comparing different groups to each other (p=0.39).
There was a significant difference in plaque characterization index on IVUS where index showed -0.0097 for CSL-111 vs. 0.0128 for placebo(p=0.01). Similarly, mean differences of angiographic coronary scores were also significnat whereby mean score change was =0.039 mm for CSL-111 vs. -0.071 mm in placebo (p=0.03).
The safety of CSL-111 was well-studied. Generally, CSL-111 was well tolerated with mild-moderate adverse events only with no varying rates between CSL-111 treatment and placebo groups except in rates of hypotension (13.8% vs. 7.1%, respectively). Elevation in liver function tests, especially after 24 hours of infusion, were all subclinical events that later normalized with no intervention. Notably, there was also a self-limited increase in unconjugated bilirubin.
Conclusion
Short-term CSL-111 infusions showed significant improvement in plaque characterization index and coronary score on angiography, but did not yield significant changes in plaque or atheroma volume. Clinically, the importance of these findings is still poorly outlined.