The Evaluation of Patients With Acute Hypertension and Intracerebral Hemorrhage With Intravenous Clevidipine Treatment (ACCELERATE)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 37
- 试验地点
- 17
- 主要终点
- Median Time to Achieve Target SBP Range (≤160 mmHg to ≥140 mmHg) Within 30 Minutes of Initiation of Clevidipine
研究概览
简要总结
The purpose of this study was 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).
详细描述
This was 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 was obtained from patients meeting the inclusion criteria before the initiation of any study-specific procedures. At screening, a clinical and neurological examination was carried out. For the purposes of this study, acute hypertension was defined as SBP >160 mmHg immediately prior to initiation of study drug. Approximately 30 to 40 patients with acute intracerebral hemorrhage (ICH) were planned to be enrolled with approximately 10 patients requiring monitoring of intracranial pressure (ICP). Infusion of study drug was initiated within 12 hours of ICH symptom onset. All eligible patients enrolled received clevidipine in an open label manner. Clevidipine was to be infused at an initial rate of 2.0 mg/h for the first 1.5 minutes. Thereafter, titration to higher infusion rates were to be attempted as needed, to obtain the target SBP range (SBP ≤160 mmHg to ≥140 mmHg). Titration to effect was 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) was attained. During the first 30 minutes, if the desired blood pressure lowering effect was not attained or maintained, an alternative intravenous (IV) antihypertensive agent(s), advised to be a different class other than calcium channel blockers, could be used with or without stopping the clevidipine infusion. The clevidipine infusion could continue for up to a maximum of 96 hours. Twenty-four hour follow-up computerized tomography (CT) scan results were recorded, including measurement of intracerebral hematoma volumes. Assessment of safety was performed throughout the treatment period and until 6 hours after termination of study drug. Patients were followed for 7 days following termination of the clevidipine infusion.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •CT evidence of intracerebral hemorrhage (diagnosis and treatment within 12 hours of symptom onset)
- •Age 18 years or older
- •Baseline systolic blood pressure (immediately prior to initiation of clevidipine) >160 mmHg measured using an arterial line. ICP-monitored patients enrolled in the sub-study were enrolled if SBP at the time of enrollment was ≤160 mmHg
- •Required antihypertensive therapy to achieve systolic blood pressure ≤160 mmHg
- •Written informed consent obtained
排除标准
- •Decision for early surgical evacuation prior to 30 minutes of clevidipine
- •Receipt of an oral antihypertensive within 2 hours prior to initiation of clevidipine
- •Treatment with a continuous infusion of an IV antihypertension agent prior to initiation of clevidipine. Bolus treatment with urapidil (Germany only), labetalol or hydralazine was permitted. ICP-monitored patients enrolled in the sub-study could be enrolled with a continuous infusion of an IV antihypertensive agent prior to the initiation of clevidipine.
- •Intracerebral hematoma considered to be related to trauma by the neurologist or neurosurgeon
- •Aneurysmal sub-arachnoid hemorrhage
- •Glasgow coma score of <5 and fixed dilated pupils
- •Expectation that the patient would not tolerate or require intravenous antihypertensive therapy for a minimum of 30 minutes
- •Known or suspected aortic dissection
- •Acute myocardial infarction on presentation
- •Positive pregnancy test or known pregnancy
- •Intolerance or allergy to calcium channel blockers
- •Allergy to soybean oil or egg lecithin
- •Known liver failure, cirrhosis or pancreatitis
- •Prior directives against advanced life support
- •Participation in other clinical research studies involving the evaluation of other investigational drugs or devices within 30 days of enrollment
研究组 & 干预措施
clevidipine
This will be a single-arm study with no reference therapy.
干预措施: clevidipine (Drug)
结局指标
主要结局
Median Time to Achieve Target SBP Range (≤160 mmHg to ≥140 mmHg) Within 30 Minutes of Initiation of Clevidipine
时间窗: Within 30 minutes of study drug initiation
The median time, in minutes, was estimated with its two-tailed 95% confidence interval from the time of the initiation of clevidipine infusion until the first observed SBP was achieved in the target range of ≤160 mmHg to ≥140 mmHg within the first 30 minutes of clevidipine treatment. If patients did not reach the blood pressure target range within the first 30 minutes, their data was considered censored at 30 minutes. If another IV and/or oral antihypertensive agent indicated for hypertension was administered less than 30 minutes prior to achieving the endpoint, the data was considered censored at the time when the additional or alternative antihypertensive agent was given.
次要结局
- Percentage of Participants Achieving a SBP of ≤160 mmHg Within 30 Minutes of Initiation of Clevidipine(Within 30 minutes of study drug initiation)
- Percent Time Blood Pressures Were Maintained Within the Target Range (Systolic Blood Pressure ≤160 mmHg to ≥140 mmHg) Over Each 24 Hour Period During Monotherapy Infusion of Clevidipine(From study drug initiation through termination (up to 96 h))
- Mean Dose of Clevidipine During the Treatment Period(Up to 96 hours)
- Proportion of Patients Requiring an Additional or Alternative Antihypertensive Agent(s) With or Without Clevidipine(Up to 96 hours)
- Percent Change From Baseline in Systolic Blood Pressure During the Initial 30 Minutes of Clevidipine Infusion(Baseline through 30 minutes post initiation of clevidipine infusion)
- Magnitude, Frequency and Duration of Systolic Blood Pressure Excursions (Calculated as Area Under the Curve [AUC]) Outside the Target Range Normalized Per Hour for the Duration of the Clevidipine Monotherapy Infusion(Duration of the study drug infusion (up to 96 hours))
- Median Dose of Clevidipine During the Treatment Period(Up to 96 hours)
- Percent Change in Heart Rate During 30 of Initiation of Clevidipine(From study drug initiation through each specified timepoint)
- The Percentage of Patients Whose Systolic Blood Pressure is <90 mmHg Within 30 Minutes of the Initiation of Clevidipine Infusion(Within 30 minutes of the initiation of study drug infusion)