March 29, 2007 - Favorable findings of the investigational drug Cleviprex (clevidipine) compared to current intravenous antihypertensive agents in controlling perioperative hypertension - a potentially harmful elevation in blood pressure just before, during and/or after surgery - were presented for the first time at a late-breaking session at the 56th Annual Scientific Session of the American College of Cardiology. The findings were from ECLIPSE, the largest safety program to date comparing intravenous antihypertensive therapies.
"This analysis from ECLIPSE showed tight perioperative blood pressure control with Cleviprex," said lead author of the presentation, Solomon Aronson, MD, Duke University Medical Center. "If approved, Cleviprex may provide a potentially important new treatment option for acute hypertension, a condition which affects nearly 3 million people in the U.S. each year."
"We are extremely pleased with the favorable findings of Cleviprex in the ECLIPSE program," said John Kelley, President and Chief Operating Officer of The Medicines Company. "Given the trial successfully met all of its primary endpoints, this marks the completion of our Phase III efforts for Cleviprex. The Medicines Company remains committed and on track to expeditiously move forward with an NDA submission before the end of June."
Study and Findings
The ECLIPSE program included a total of 1,964 cardiac surgery patients each enrolled in one of three randomized, open-label trials comparing Cleviprex to current intravenous antihypertensive agents: nitroglycerin, sodium nitroprusside or nicardipine (ECLIPSE-NTG, ECLIPSE-SNP and ECLIPSE-NIC trials, respectively). Beginning just before surgery, investigators monitored patients' blood pressure (BP) and administered the assigned antihypertensive agent, at their discretion, if BP became too high. Based on each patient's BP response for 24 hours after initiating the therapy, investigators determined "BP excursions" - how much and how long systolic BP went above or below predefined, acceptable perioperative BP ranges.
The ECLIPSE analysis evaluated BP excursions from data pooled from all three studies and from the individual studies. In the pooled analysis, for the widest predefined acceptable perioperative BP range of 75-145 mm Hg pre- and post-operatively and 65-135 mm Hg during surgery, Cleviprex resulted in approximately half the BP excursion compared to the other agents (3.8 vs. 7.8 mm Hg x min/h, p = 0.0004). Results for the narrowest BP range of 105-145 mm Hg pre- and post-operatively and 95-135 mm Hg during surgery also favored Cleviprex (87.7 vs. 111.5 mm Hg x min/h, p = 0.0002).
In the individual ECLIPSE-NTG and ECLIPSE-SNP studies, for the widest BP range, Cleviprex resulted in approximately half the BP excursion compared to nitroglycerin (4.14 vs. 8.87 mm Hg x min/h, p = 0.0006) and sodium nitroprusside (4.37 vs. 10.50 mm Hg x min/h, p = 0.0027), respectively. At this BP range, there was no significant difference in BP excursions for Cleviprex vs. nicardipine (1.76 vs. 1.79 mm Hg x min/h, p = 0.8508), however that comparison was restricted to the post-operative period only, since nicardipine is not generally used before or during surgery due to its relatively slow onset and offset of action. Other standard intravenous BP control agents were administered, as deemed appropriate, just before or during surgery in the ECLIPSE-NIC trial.
For the narrowest BP range, Cleviprex also resulted in less BP excursion compared to sodium nitroprusside (100.17 vs. 127.87 mm Hg x min/h, p = 0.0068), nicardipine (76.5 vs. 101.59 mm Hg x min/h, p = 0.0231), and nitroglycerin (83.74 vs. 108.57 mm Hg x min/h, p = 0.0556).
The ECLIPSE-SNP trial also showed that the rate of death was significantly lower with Cleviprex than with sodium nitroprusside (1.7% vs. 4.7%, p = 0.045). Other than this difference, the primary endpoints - rates of death, stroke, heart attack and kidney dysfunction - were similar for Cleviprex compared to the other three agents.