Clevidipine in the Treatment of Blood Pressure in Patients With Acute Heart Failure (PRONTO)

The Medicines Company

Status and phase: Completed; Phase 3

Conditions: Hypertension; Heart Failure

Treatments: Drug: Standard of Care IV antihypertensive; Drug: Clevidipine

Study type: Interventional

Funder types: Industry

Identifiers

NCT00803634

TMC-CLV-08-01 (Other Identifier)

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 117 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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

Exclusion criteria

• 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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117 participants in 2 patient groups

Clevidipine

Experimental group

Description:

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.

Treatment:

Drug: Clevidipine

Standard of Care IV antihypertensive

Active Comparator group

Description:

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.

Treatment:

Drug: Standard of Care IV antihypertensive