A Safety and Efficacy Study of Blood Pressure Control in Acute Heart Failure - A Pilot Study (PRONTO)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 117
- 试验地点
- 13
- 主要终点
- Time to First Achieve Initial Prespecified SBP Target Range and 15% Reduction From Baseline Within First 30 Minutes
研究概览
简要总结
The purpose of this study was to evaluate the efficacy and safety of intravenous (IV) clevidipine as compared with standard of care IV antihypertensive agents for blood pressure (BP) lowering in patients with acute heart failure and elevated BP.
详细描述
This study was an open-label randomized efficacy and safety pilot trial in patients with acute heart failure (AHF) and hypertension (systolic blood pressure [SBP] ≥160 mm Hg) requiring parenteral antihypertensive therapy. Eligible patients were randomized to receive clevidipine or standard of care (SOC) intravenous antihypertensive treatment in an open-label manner in a ratio of 1:1. At the time of randomization, a patient-specific, prespecified SBP target range was determined and be recorded, prior to study drug treatment. Information on the dosing regimen, use of additional or alternative agents and transition to oral therapy if needed is detailed in the study 'ARM' and 'INTERVENTION' sections.
A Data Safety Monitoring Board was utilized periodically throughout the study to monitor the safety of patients. Adverse events were assessed for 7 days post-study randomization or hospital discharge, whichever occured first. Serious adverse events (SAEs) were assessed for 30 days following study randomization. Subjects were contacted by telephone or in person up to 5 days after their 30-day time point to determine if any SAEs occurred following study drug treatment and to follow up on the Heath Economic assessments.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- •Age 18 years or older
- •Presentation consistent with acute heart failure and pulmonary congestion on physical examination as evidenced by rales
- •Baseline systolic blood pressure (immediately prior to initiation of study drug) of ≥160 mm Hg
- •Dyspnea score (sitting) of at least 5 on a 10 cm visual analog scale (VAS)
- •Required IV antihypertensive therapy to lower blood pressure
- •Written informed consent
排除标准
- •Administration of an agent (IV or oral) for the treatment of elevated BP within the previous 2 hours of randomization. (Previous short-acting non-IV nitrates, continuous positive airway pressure (CPAP), and bi-level positive airway pressure (BiPAP) were permitted)
- •Chest pain and/or electrocardiogram with ST segment changes consistent with acute coronary syndrome
- •Known or suspected aortic dissection
- •Acute myocardial infarction within the prior 14 days
- •Dialysis-dependant renal failure
- •Requirement for immediate endotracheal intubation
- •Positive pregnancy test, known pregnancy or breast feeding female
- •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
Clevidipine (0.5 mg/mL in 20% lipid emulsion) was administered intravenously via a single dedicated line to all patients randomized to the clevidipine arm. Clevidipine was infused at an initial rate of 2 mg/h for the first 3 minutes. If blood pressure was not in the target range at 3 minutes, clevidipine was titrated to effect thereafter by doubling the dose every 3 min, per physician discretion and as tolerated by the patient until the desired effect until the SBP target range was attained. Once target range was achieved, the infusion rate could be increased or decreased as needed to maintain blood pressure for minimum of 30 minutes and a maximum duration of 96 hours. The minimum infusion rate was 1 mg/h and maximum infusion rate was 32 mg/h.
干预措施: Clevidipine (Drug)
Standard of Care IV antihypertensive
For patients randomized to standard of care (SOC) IV antihypertensive treatment, a continuous infusion of an intravenous antihypertensive agent represented standard of care. The selection of treatment was at the discretion of the investigator. The infusion was to be administered according to the institution's treatment practice.
干预措施: Standard of Care IV antihypertensive (Drug)
结局指标
主要结局
Time to First Achieve Initial Prespecified SBP Target Range and 15% Reduction From Baseline Within First 30 Minutes
时间窗: Initiation of study drug through the initial 30-minutes
Time to first achieve the initial pre-specified systolic blood pressure (SBP) target range and a 15% SBP reduction from baseline is the time in minutes between the initiation of study medication and the time the patient first achieved both components. Median time was estimated using Kaplan Meier method. 95% two-sided confidence interval of the median time is from 'Simon and Lee, 1982'. If patients did not reach both components within 30 minutes from the initial treatment with study medication, or another antihypertensive agent was administered, the patient was censored at 30 minutes or the time when another antihypertensive agent is given, whichever came first.
Percentage to First Achieve Initial Prespecified SBP Target Range [≥20 mm Hg and ≤40 mm Hg Apart] and 15% Reduction From Baseline Within First 30 Minutes
时间窗: Initiation of study drug through the initial 30-minutes
Analysis of the percentage of patients achieving both components of this composite endpoint (attainment of the initial prespecified SBP target range and a 15% reduction in SBP from baseline) was calculated within each treatment group using the number of mITT patients achieving the SBP reduction goal divided by the number of mITT patients, and multiplied by 100.
次要结局
- Percentage Reaching Prespecified Target Range Without Falling Below Lower Limit of Target Range Within First 30 Minutes(Initiation of study drug through the initial 30-minutes)
- SBP Area Under the Curve (AUC) Outside Prespecified Target Range(Initiation of study drug through end of monotherapy (up to 96 hours))
- Percentage Falling Below Lower Limit of SBP Target Range Within First 30 Minutes(Initiation of study drug through the initial 30-minutes)
- Percentage Falling Below Lower Limit of SBP Target Range at Any Time During Study(Initiation through termination of study drug (up to 96 hours))
- Change From Baseline in Dyspnea (Measured By VAS) at Each Time Point(Baseline (immediately prior to study drug administration) through 1 hour after study drug termination)
- Time to Use Other IV Antihypertensives During the Study Drug Administration(Initiation of study drug through any other concomitant IV antihypertensive agent administered, up to 96 hours)
- Percentage of Patients Who Received Any Alternative IV Antihypertensive Drug at Any Time During Study Drug Treatment(Initiation through termination of study drug (up to 96 hours))
- Percentage of Patients With at Least One Episode of SBP < 90 mm Hg During Study Drug Administration (up to 96 Hours)(Initiation through termination of study drug (up to 96 hours))
- Number of Patients That Require Intubation During Study Drug Administration up to 96 Hours(Initiation through termination of study drug (up to 96 hours))