A Safety and Efficacy Study of Blood Pressure Control in Acute Aortic Emergencies - A Pilot Study (PROMPT)

• The primary objective of this pilot study is to evaluate the efficacy of an IV infusion of clevidipine as an antihypertensive for BP lowering in patients with AAE and elevated BP. [ Time Frame: 1 Hour ] [ Designated as safety issue: No ]
  

• The secondary objectives of the study are to evaluate the safety of an IV infusion of clevidipine as an antihypertensive for BP lowering in patients with AAE and elevated BP. [ Time Frame: 48 Hours ] [ Designated as safety issue: Yes ]
  

Drug: clevidipine.
For the purposes of this study, clevidipine is to be administered via IV infusion at a starting dose of 2 mg/h (4 mL/hr) for 3 minutes and thereafter titrated to the desired BP lowering effect to achieve the SBP goal of < 120 mmHg. At the discretion of the investigator, it is recommended that clevidipine be titrated, as tolerated by the patient, in doubling increments every 3 minutes in order to achieve the desired BP lowering effect. The maximum infusion rate may not exceed 32 mg/h (64 mL/hr). Clevidipine infusion may be titrated upwards and downwards, keeping in mind that it has a very rapid onset of effect on BP, i.e., 2-4 minutes. Although the clevidipine infusion rate may be decreased at the discretion of the investigator in order to achieve/maintain the SBP goal, the minimum infusion rate should not be lower than 1 mg/h (2 mL/hr). Clevidipine infusion may be terminated at any time for a safety reason or at the investigator's discretion.

This study will be a Phase IV, open label, non-randomized efficacy and safety pilot trial in patients with AAE and hypertension requiring parenteral antihypertensive therapy. For the purpose of this study hypertension is defined as SBP ≥120 mm Hg immediately prior to clevidipine administration.

Patients will be enrolled at the Methodist DeBakey Heart & Vascular Center in Houston, TX. Enrollment of approximately 30 patients is anticipated and enrollment will continue until this goal is met.

The study will include three separate periods: Screening Period, Treatment Period (up to 48 hours) and Follow-up Period (up to 7 days or hospital discharge, whichever occurs first) representing approximately a maximum of 7 days on study. Eligible patients will be enrolled to receive clevidipine IV antihypertensive treatment (study drug) in an open label manner.

Clevidipine will be infused at an initial rate of 2 mg/h (4 mL/hr) for the first 3 minutes. Thereafter, titration to higher infusion rates can be attempted as needed to obtain the target SBP goal < 120 mmHg. Titration to effect is to proceed by doubling the dose every 3 minutes, up to a maximum of 32 mg/h (64 mL/hr), until the SBP < 120 mmHg is attained.

If the desired BP lowering effect is not attained with study drug within 1 hour or not maintained thereafter, an alternative antihypertensive agent may be used, with or without stopping clevidipine IV antihypertensive infusion. The alternative agent should be used per institutional treatment practice. During the initial 1 hour of the treatment period, however, clevidipine IV antihypertensive treatment should be administered as monotherapy until 1 hour post initiation of study drug. The use of an alternative antihypertensive agent(s) is discouraged and limited to where medically necessary to maintain patient safety.

Clevidipine IV antihypertensive infusion may continue for a maximum of 48 hours. However, if medically warranted, clevidipine treatment may continue beyond 48 hours at the investigator's discretion.