Clinical trial NCT01938547: Assessment of Efficacy, Safety and Dosing of Clevidipine in Pediatric Participants Undergoing Surgery (PIONEER)
Official title: Open Label Study to Assess the Efficacy, Safety and Dosing of Clevidipine in Pediatric Patients Undergoing Surgery
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Pediatric Perioperative Blood Pressure Management
Keywords: perioperative
blood pressure
pediatrics
pediatric surgery
Lead sponsor: Chiesi Farmaceutici S.p.A.
Sponsor class: INDUSTRY
First posted: 2013-09-10
Enrollment: 22
Sex: ALL
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Evaluate the efficacy, safety, and dosing of clevidipine as an intravenous (IV) infusion for blood pressure (BP) management in paediatric participants in the perioperative setting.

Detailed description: This was 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 IV infusion of antihypertensive therapy for the management of blood pressure was expected.

The reason for initiating clevidipine administration was to keep blood pressure within a pre-specified range during surgery.

After the study completion for Cohort 1 (adolescent patients 12 to less than 18 years), the PIONEER study was placed on partial clinical hold by the FDA; later, the study was terminated by the sponsor. Enrolment of the subsequent cohorts did not take place; results are presented for Cohort 1 only.

Eligibility criteria: 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

Primary outcomes:
measure: Efficacy: Median Time to Attain the Initial Pre-specified Target SBP Range
timeFrame: During the first 30 minutes of clevidipine infusion start (baseline).
measure: Efficacy: Number and Percentage of Participants Achieving the Initial Pre-specified Target SBP Range -- During First 30 Min of Clevidipine Infusion
timeFrame: During the first 30 minutes of clevidipine infusion start (baseline).
measure: Efficacy: Total Dose to Attain the Initial Pre-specified Target SBP Range
timeFrame: During the first 30 minutes of clevidipine infusion start (baseline).
measure: Pharmacology: Pharmacodynamic Variable -- Infusion Rate
timeFrame: Duration of clevidipine infusion (minimum of 30 minutes up to a maximum 96 hours).
measure: Pharmacology: Clevidipine -- Tmax
timeFrame: From 30 minutes before start of infusion up to termination of infusion (minimum of 9 hours up to a maximum of 96 hours).
measure: Pharmacology: Clevidipine -- Cmax
timeFrame: From 30 minutes before start of infusion up to termination of infusion (minimum of 9 hours up to a maximum of 96 hours).
measure: Pharmacology: Clevidipine -- Area Under the Concentration Curve (AUCall)
timeFrame: From 30 minutes before start of infusion up to termination of infusion (minimum of 9 hours up to a maximum of 96 hours).
measure: Pharmacology: Clevidipine -- Area Under the Concentration Curve Infinity (AUCinf)
timeFrame: From 30 minutes before start of infusion up to termination of infusion (minimum of 9 hours up to a maximum of 96 hours).
measure: Pharmacology: Clevidipine -- Volume of Distribution (Vd)
timeFrame: From 30 minutes before start of infusion up to termination of infusion (minimum of 9 hours up to a maximum of 96 hours).
measure: Pharmacology: Clevidipine -- Total Clearance (CL)
timeFrame: From 30 minutes before start of infusion up to termination of infusion (minimum of 9 hours up to a maximum of 96 hours).
measure: Pharmacology: Clevidipine -- Half-Life (T1/2)
timeFrame: From 30 minutes before start of infusion up to termination of infusion (minimum of 9 hours up to a maximum of 96 hours).
Secondary outcomes:
measure: Efficacy: Percent Change in SBP From Baseline at Each Time Point -- During First 30 Min of Infusion Start (Baseline)
timeFrame: From infusion start (baseline) to 30 minutes post baseline.
measure: Efficacy: Percent Change From Baseline in SBP -- Hourly Measurements -- From 30 Min to 6 Hours of Infusion Start (Baseline)
timeFrame: At each hour from 30 minutes post-clevidipine infusion start (baseline) to 6 hours from baseline.
measure: Efficacy: Percent Change in SBP From Baseline at Each Time Point -- From Cessation of Study Drug Infusion up to 12 Hours
timeFrame: During the first 12 hours (measured at each hour) after cessation of clevidipine infusion.
measure: Efficacy: Number and Percentage of Patients Falling Below the Target Systolic Blood Pressure Range Lower Limit -- During the First 30 Minutes and During the Entire Drug Treatment Period of Clevidipine Infusion
timeFrame: During the first 30 minutes and during the entire drug treatment period (up to a maximum of 96 hours of clevidipine infusion).
measure: Efficacy: Number and Percentage of Participants in Whom the SBP Was Within Target Range at Each Hour After the First 30 Minutes of Clevidipine Infusion (up to 6 Hours)
timeFrame: From 30 minutes after infusion start (baseline) and up to 6 hours post-clevidipine infusion.
measure: Efficacy: Percent Change From Baseline in Heart Rate (HR) -- During First 30 Min of Infusion
timeFrame: From infusion start (baseline) to 30 minutes post baseline.
measure: Efficacy: Percent Change From Baseline in Heart Rate (HR).
timeFrame: At each hour after 30 minutes post-clevidipine infusion start (baseline) and up to 6 hours.
measure: Efficacy: Percent Change From Baseline in Heart Rate (HR) -- From Cessation of Study Drug Infusion up to 12 Hours
timeFrame: At each hour after cessation of clevidipine infusion (up to 12 hours).
measure: Efficacy: Number and Percentage of Participants Requiring Rescue Therapy
timeFrame: Minimum of 30 minutes up to a maximum of 96 hours post infusion start (baseline).
measure: Efficacy: Number and Percentage of Participants Discontinuing Due to Adverse Events
timeFrame: Minimum of 30 minutes up to a maximum of 96 hours post infusion start (baseline).
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford Medical Center
state: California
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
Study officials:
affiliation: Nationwide Children's Hospital
name: Joseph D Tobias, MD
role: PRINCIPAL_INVESTIGATOR
References: