Clevidipine in the Treatment of Patients With Acute Hypertension and Intracerebral Hemorrhage (ACCELERATE)
The purpose of this study is to determine the efficacy and safety of clevidipine for treating acute hypertension (high blood pressure, defined as systolic blood pressure >160 mmHg) in patients with intracerebral hemorrhage (i.e., bleeding in the brain; stroke).
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||The Evaluation of Patients With Acute Hypertension and Intracerebral Hemorrhage With Intravenous Clevidipine Treatment|
- The Median Time to Achieve the Target BP (Systolic Blood Pressure ≤160 mmHg to ≥140 mmHg) Within 30 Minutes of the Initiation of Clevidipine Infusion. [ Time Frame: Within 30 minutes of the initiation of study drug infusion ] [ Designated as safety issue: No ]
- The Percentage of Patients Who Reach a Systolic Blood Pressure of ≤160 mmHg Within 30 Minutes of the Initiation of Clevidipine Infusion [ Time Frame: Within 30 minutes of the initiation of study drug infusion ] [ Designated as safety issue: No ]
- Percent Change From Baseline in Systolic Blood Pressure During the Initial 30 Minutes of Clevidipine Infusion [ Time Frame: Baseline through 30 minutes post initiation of clevidipine infusion ] [ Designated as safety issue: No ]Over the initial 30 minutes of the treatment period, the percent change was measured from SBP measurements collected every 3 minutes. Decreases in SBP from baseline were observed over the course of this time period. The outcome measure reported below represents the percent change at 30 minutes after the initiation of clevidipine infusion.
- Magnitude, Frequency and Duration of Systolic Blood Pressure Excursions (Calculated as Area Under the Curve) Outside the Target Range Normalized Per Hour for the Duration of the Clevidipine Monotherapy Infusion [ Time Frame: Duration of the study drug infusion (up to 96 hours) ] [ Designated as safety issue: No ]Total AUC-SBP captures the magnitude and duration of SBP either above the upper limit of the target SBP range at 160 mm Hg, or below the lower limit of 140 mm Hg, normalized per hour for the duration of clevidipine infusion. A larger value for AUC-SBP indicates greater SBP variability outside the target range.outside the range, or both.
- Percent Time Blood Pressures Were Maintained Within the Target Range (Systolic Blood Pressure ≤160 mmHg to ≥140 mmHg) Over Each 24 Hours During Monotherapy Infusion of Clevidipine [ Time Frame: 0-24 hours ] [ Designated as safety issue: No ]
Percent times that SBP was maintained in range were obtained for each 24-hour period of monotherapy clevidipine infusion through 96 hours. For purposes of this analysis, SBP data were available from all mITT patients for the overall infusion period and from 0 to ≤24 hours of infusion (Percent time SBP in or outside target range (≤160 mm Hg to ≥140 mm Hg). For the additional 24-hour timeframes through 96 hours, data was available for only 8 patients from 24 to ≤48 hours, 4 patients from 48 to ≤72 hours, and 1 patient from 72 to
≤96 hours due to the infusion durations across patients. The data presented below is for first 24 hours of monotherapy clevidipine infusion.
- Mean Dose of Clevidipine During the Treatment Period [ Time Frame: Up to 96 hours ] [ Designated as safety issue: No ]From clevidipine initiation to the end of clevidipine treatment
- Proportion of Patients Requiring an Additional or Alternative Antihypertensive Agent(s) With or Without Clevidipine [ Time Frame: Up to 96 hours ] [ Designated as safety issue: No ]Additional or alternative antihypertensive agent(s) comprise the use of other antihypertensive agent(s) either with clevidipine (additional) or in place of clevidipine (alternative) for the indication of hypertension from the time of clevidipine initiation to clevidipine termination. For purposes of this analysis, additional or alternative antihypertensive agents did not include oral antihypertensives that were administered in order to transition IV clevidipine-treated patients to oral therapy during the transition period of the study.
- Percent Change in Heart Rate at 30 Minutes of From Time of Clevidipine Infusion [ Time Frame: Change at 30 minutes from baseline ] [ Designated as safety issue: Yes ]Multiple timepoints were assessed(minutes 1, 2, 3, 4, 5, 10, 15, 20, 30)for analysis of percent change in heart rate during the initial 30 minutes. However, the data presented below represents the percent change in heart rate assessed at 30 minutes from baseline taken immediately prior to clevidipine administration.
- The Percentage of Patients Whose Systolic Blood Pressure is <90 mmHg Within 30 Minutes of the Initiation of Clevidipine Infusion [ Time Frame: Within 30 minutes of the initiation of study drug infusion ] [ Designated as safety issue: Yes ]
|Study Start Date:||April 2008|
|Study Completion Date:||April 2010|
|Primary Completion Date:||April 2010 (Final data collection date for primary outcome measure)|
This will be a single-arm study with no reference therapy.
Clevidipine butyrate injectable emulsion(0.5 mg/mL in 20% lipid emulsion; 100 mL bottles) will be administered intravenously to all patients via a single dedicated line.
Clevidipine will be infused at an initial rate of 2.0 mg/h for the first 1.5 minutes. Thereafter, titration to higher infusion rates can be attempted as needed to obtain the target systolic blood pressure (SBP) range (SBP ≤160 mmHg to ≥140 mmHg). Titration to effect is to proceed by doubling the dose every 1.5 minutes, up to a maximum of 32.0 mg/h, until the desired effect (SBP within the target range) is attained. The clevidipine infusion rate may increased or decreased to maintain systolic blood pressure for up to a maximum of 96 hours.
Other Name: Cleviprex, clevidipine butyrate injectable emulsion
This is a multicenter, single-arm, non-blinded dose titration efficacy and safety trial evaluating the ability of clevidipine, a vascular-selective L-type calcium channel antagonist, to rapidly control acute hypertension in patients with intracerebral hemorrhage. Informed consent will be obtained from patients meeting the inclusion criteria before the initiation of any study-specific procedures. At screening a clinical and neurological examination will be carried out. For the purposes of this study, acute hypertension will be defined as SBP >160 mmHg immediately prior to initiation of study drug. Approximately 30 to 40 patients with acute ICH will be enrolled with approximately 10 patients requiring ICP monitoring. Infusion of study drug will be initiated within 12 hours of ICH symptom onset. All eligible patients will be enrolled to receive clevidipine in an open label manner. Clevidipine will be infused at an initial rate of 2.0 mg/h for the first 1.5 minutes. Thereafter, titration to higher infusion rates can be attempted as needed to obtain the target SBP range (SBP ≤160 mmHg to ≥140 mmHg). Titration to effect is to proceed by doubling the dose every 1.5 minutes, up to a maximum of 32.0 mg/h, until the desired effect (SBP within the target range) is attained. During the first 30 minutes, if the desired blood pressure lowering effect is not attained or maintained, an alternative IV antihypertensive agent(s), advised to be a different class other than calcium channel blockers, may be used with or without stopping the clevidipine infusion. The clevidipine infusion may continue for up to a maximum of 96 hours. Twenty-four hour follow-up CT scan results will be recorded, including measurement of intracerebral hematoma volumes. Assessment of safety will be performed throughout the treatment period and until 6 hours after termination of study drug. Patients will be followed for 7 days following termination of the clevidipine infusion.
|United States, District of Columbia|
|Washington Hospital Center|
|Washington, District of Columbia, United States, 20010-2975|
|United States, Hawaii|
|The Queens Medical Center|
|Honolulu, Hawaii, United States, 96813|
|United States, Maryland|
|The John Hopkins Hospital|
|Baltimore, Maryland, United States, 21287|
|United States, Michigan|
|Henry Ford Hospital|
|Detroit, Michigan, United States, 48202|
|United States, New York|
|Columbia University Medical Center|
|New York, New York, United States, 10032|
|United States, North Carolina|
|Duke University Medical Center|
|Durham, North Carolina, United States, 27710|
|Guilford Neurologic - Moses H Cone Health System|
|Greensboro, North Carolina, United States, 27405|
|United States, Ohio|
|Cleveland Clinic Hospitals|
|Cleveland, Ohio, United States, 44195|
|The Ohio State University|
|Columbus, Ohio, United States, 43210|
|United States, Pennsylvania|
|Thomas jefferson University Stroke Research|
|Philadelphia, Pennsylvania, United States, 19107|
|United States, South Carolina|
|Main Medical Center|
|Charleston, South Carolina, United States, 29425|
|Medical University of South Carolina|
|Charleston, South Carolina, United States, 29425|
|United States, Texas|
|The University Health Science Center at S.A.|
|San Antonio, Texas, United States, 78229-3900|
|United States, Utah|
|Intermountain Medical Center|
|Murray, Utah, United States, 84157|
|Liebigstraße 22a, Leipzig, Germany, D-04103|
|Erlangen, Germany, D91054|
|Heidelberg, Germany, D69120|
|Principal Investigator:||Carmelo Graffagnino, MD||Duke University|