Assessment of Efficacy, Safety and Dosing of Clevidipine in Pediatric Participants Undergoing Surgery (PIONEER) (PIONEER)

Open Label Study to Assess the Efficacy, Safety and Dosing of Clevidipine in Pediatric Patients Undergoing Surgery

To evaluate the efficacy, safety and dosing of an intravenous (IV) infusion of clevidipine for blood pressure (BP) management in pediatric participants in the perioperative setting.

Study Overview

• Status: Withdrawn
• Conditions: Pediatric Perioperative Blood Pressure Management
• Intervention / Treatment: Drug: clevidipine

Detailed Description

This is an open label study to assess, in a stepwise approach across 4 age cohorts from oldest to youngest (birth to <age 18), the efficacy and safety of clevidipine exposure for a minimum of 30 minutes and up to a maximum of 96 hours in pediatric participants undergoing a surgical procedure with anesthesia for greater than or equal to 1 hour and for whom parenteral intravenous antihypertensive therapy for the management of blood pressure is expected.

• Study Type: Interventional
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford Medical Center
  • Ohio
    • Columbus, Ohio, United States, 43205
      • Nationwide Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 17 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Less than 18 years of age
• Written informed consent obtained before initiation of any study-related procedures
• The enrolling physician determines that the participant will likely require a 15% reduction in BP during the perioperative course
• Intra-arterial line is available for blood pressure monitoring
• Surgical procedure requiring a minimum of 1 hour of anesthesia, in which IV antihypertensive therapy to control BP for at least 30 minutes is anticipated

Exclusion Criteria:

• Administration of an IV or oral antihypertensive agent within 2 hours prior to study drug administration
• Congenital heart disease described as single ventricle
• Evidence of liver failure, severe liver disease, pulmonary disease (e.g. uncontrolled asthma), hyperlipidemia, lipoid nephrosis, lipid dysfunction or acute pancreatitis
• Allergy to soya bean oil or egg lecithin
• Known to be intolerant to calcium channel blockers
• Hemophilia or blood coagulation disorders
• Any serious medical condition which, in the opinion of the investigator, is likely to interfere with study procedures
• Clinically significant abnormal physical findings at the screening evaluation
• Any serious surgical or medical condition which, in the opinion of the investigator, is likely to interfere with study procedures or with the pharmacokinetics or pharmacodynamics of the study drug
• Participant is terminally ill (death likely to occur within 48 hours)
• Use of Methylphenidate, calcium channel blockers, Aripiprazole and other atypical anti- psychotics and antihypertensives used for BP control within 2 hours prior to study drug initiation
• Positive serum or urine pregnancy test for any female of child bearing potential
• Participation in other clinical research studies involving the evaluation of other investigational drugs or devices within 30 days of enrollment
• Participants who, for any reason, are deemed by the Investigator to be inappropriate for this study
• Participant is a relative of the Investigator or his/her deputy, research assistant, pharmacist, study coordinator, other staff directly involved in the conduct of the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: clevidipine; An initial clevidipine IV infusion dose for the adolescent cohort has been specified per protocol. The initial dose for each of the subsequent age cohorts will be modified if necessary, based on the recommendation of the Data and Safety Monitoring Board (DSMB). Following the initial dose, clevidipine will be up-titrated every 1.5 minutes, according to participant need, to achieve a systolic blood pressure (SBP) within the pre-specified SBP target range. Doses may be increased by less than doubling, and the time between dose adjustments may be lengthened, as the target blood pressure is approached. The infusion rate may be maintained for up to 96 hours, once the participant's SBP is within the target range, and titrated as necessary to maintain blood pressure within the range.

Drug: clevidipine; Other Names: Cleviprex; clevidipine butyrate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Efficacy: Median time to attain the initial pre-specified target SBP range (≥20 mm Hg and ≤ 40 mm Hg apart)	During the first 30 minutes of clevidipine infusion
Efficacy: Dose to attain the initial pre-specified target SBP range (≥20 mm Hg and ≤ 40 mm Hg apart)	During the first 30 minutes of clevidipine infusion
Efficacy: Percentage of participants achieving the initial pre-specified target SBP range	During the first 30 minutes of clevidipine infusion
Pharmacology: Pharmacokinetic variables [half-life, Area Under the Curve (AUC), volume of distribution, clearance] established by noncompartmental analysis or sparse population methodology	Through 8 hours post-termination of clevidipine infusion (minimum of 9 hours up to a maximum of approximately 4 1/2 days)
Pharmacology: Pharmacodynamic variables (relationship between change from baseline in SBP versus blood concentration and infusion rate)	Duration of clevidipine infusion (minimum of 30 minutes up to a maximum 96 hours)
Safety: Safety of a prolonged infusion of clevidipine assessed through clinical laboratory parameters, adverse events and serious adverse events (SAEs)	Through 7 days post-termination of clevidipine infusion (minimum of approximately 7 1/2 days up to a maximum of approximately 11 1/2 days)

Secondary Outcome Measures

Outcome Measure	Time Frame
Efficacy: The percentage of participants who reach the initial pre-specified target SBP range without falling below the lower limit of the pre-specified target range	During the first 30 minutes of clevidipine infusion
Efficacy: The percentage of participants in whom the SBP falls below the lower limit of the pre-specified target range at any time	During the first 30 minutes of clevidipine infusion
Efficacy: The percentage of participants in whom the SBP falls below the lower limit of the pre-specified target range at any time during the entire study drug treatment period	Minimum of 30 minutes up to a maximum of 96 hours
Efficacy: The percentage of participants in whom the SBP is within target range at each hour after the first 30 minutes of clevidipine infusion	30 minutes post-clevidipine infusion through termination of clevidipine infusion (minimum of <1 minute up to a maximum of 95 1/2 hours)
Efficacy: The percentage of participants who require rescue therapy (i.e. receive any alternative IV antihypertensive drug) at any time during the study drug treatment period	Minimum of 30 minutes up to a maximum of 96 hours
Efficacy: Percent change in SBP from baseline at each time point	Every 1.5 minutes during the first 30 minutes of clevidipine infusion (approximately 20 measurements)
Efficacy: Percent change from baseline in SBP	At each hour after 30 minutes post-clevidipine infusion through termination of clevidipine infusion (up to a maximum of 96 measurements)
Efficacy: Percent change from baseline in SBP over the first 8 hours post-study drug termination	During the first 8 hours after termination of clevidipine infusion
Efficacy: Percent change from baseline in heart rate	During the first 30 minutes of clevidipine infusion
Efficacy: Percent change from baseline in heart rate	30 minutes post-clevidipine infusion through termination of clevidipine infusion (minimum of <1 minute up to a maximum of 95 1/2 hours)

Collaborators and Investigators

• Sponsor: Chiesi Farmaceutici S.p.A.
• Investigators: Principal Investigator: Joseph D Tobias, MD, Nationwide Children's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2014
• Primary Completion (Actual): February 20, 2024
• Study Completion (Actual): February 20, 2024

Study Registration Dates

• First Submitted: August 30, 2013
• First Submitted That Met QC Criteria: September 4, 2013
• First Posted (Estimated): September 10, 2013

Study Record Updates

• Last Update Posted (Actual): April 5, 2024
• Last Update Submitted That Met QC Criteria: April 4, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: pediatrics; blood pressure; pediatric surgery; perioperative
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Membrane Transport Modulators; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Clevidipine
• Other Study ID Numbers: MDCO-CLV-12-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No