Intubated and Mechanically Ventilated Pediatric SubjectsPhase 2NCT00652028

Pharmacokinetics and Pharmacodynamics of Dexmedetomidine in Pediatrics Subjects

A Phase 2 study testing Dexmedetomidine, midazolam; fentanyl in people with Intubated and Mechanically Ventilated Pediatric Subjects, run by Hospira, now a wholly owned subsidiary of Pfizer at 9 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

The objective of this study is to characterize the pharmacokinetic and pharmacodynamic profile of dexmedetomidine administered as an intravenous loading dose followed by a continuous intravenous infusion in pediatric subjects ages ≥2 through <17 years old. Read more about this study

Who is it for?: Ages 2 to 16 years
Conditions the study is for: Intubated and Mechanically Ventilated Pediatric Subjects
What is being tested?: Dexmedetomidine, midazolam; fentanyl
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 69 participants
Where: 9 sitesin 2 countries
Study dates: Nov 2008to Apr 2010
Phase: Phase 2

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 2 to 16 years
All sexes
No healthy volunteers
Child

Who may be able to join

Initially intubated and mechanically ventilated pediatric subjects in an intensive care setting anticipated to require a minimum of 6 hours of continuous intravenous sedation.
Age: subjects must fit into one of the following age ranges at screening:
≥2 years old through <6 years old
≥6 years old through <17 years old
If female, subject is non-lactating and is either:
Not of childbearing potential, defined as pre-menarche, or surgically sterile due to bilateral tubal ligation, bilateral oophorectomy or hysterectomy.
Of childbearing potential but is not pregnant at time of baseline.
Subject's parent(s) or legal guardian(s) has/have voluntarily signed and dated the informed consent document approved by the Institutional Review Board. Assent will be obtained where age-appropriate and according to state regulations.

Who cannot join

Pediatric subjects with neurological conditions that prohibit an evaluation of sedation
Diminished consciousness from increased intracranial pressure.
Extensive brain surgery (surgery requiring intracranial pressure monitor).
Diminished cognitive function per PI's discretion.
Subjects with immobility from neuromuscular disease or continuous infusion of neuromuscular blocking agents.
Weight <10 kg.

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Subjects with second degree or third degree heart block unless subject has a pacemaker or pacing wires.
Hepatic impairment Serum glutamic pyruvic transaminase/Alanine aminotransferase (SGPT/ALT) >100 U/L
Hypotension based on repeat assessments prior to starting study drug:
Age ≥2 years old through ≤12 years old: systolic blood pressure (SBP) <80 mmHg
Age >12 years old through <17 years old: SBP <90 mmHg
Pre-existing bradycardia prior to starting study drug defined as:
Age ≥2 years old through ≤6 years old: ≤70 beats per minute (bpm)
Age >6 years old through ≤12 years old: ≤60 bpm
Age >12 years old through ≤16 years old: ≤50 bpm
Acute thermal burns involving more than 15 percent total body surface area.
Subjects who have a known allergy to dexmedetomidine, midazolam (MDZ) or fentanyl.
Subjects with a life expectancy that is <72 hours.
Subjects that are expected to have hemodialysis (continuous hemofiltration) or peritoneal dialysis within 48 hours.
Subjects who have been treated with α-2 agonists/antagonists within two weeks.
Subjects with a spinal cord injury above T5.
Subjects who have received another investigational drug within the past 30 days.
Subjects on nicotine replacement therapy.
Subjects who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of this clinical study.

Trial locations and contacts

9 sites in 2 countries.

Country

City, postcode or hospital

9 sites in 2 countries

United States8 sites

Women and Children's Hospital of Buffalo
Buffalo, New York, 14222
University Hospitals Medical Center
Cleveland, Ohio, 44106
Duke University Medical Center
Durham, North Carolina, 27710
University of Louisville/Kosair Children's Hospital
Louisville, Kentucky, 40202
Miami Children's Hospital
Miami, Florida, 33155
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, 15213
Virginia Commonwealth University
Richmond, Virginia, 23219

Other trials in United States

Guatemala1 site

Unidad Cirugia Cardiovascular de Guatemala
Guatemala City

Other trials in Guatemala

About this study

Official title: A Phase II, Open-Label, Multicenter, Escalating Dose, Study to Determine Pharmacokinetic and Pharmacodynamic Profile of Dexmedetomidine in Pediatric Subjects Ages ≥ 2 Through < 17 Years Old

Read the detailed description

This is a phase II, open-label, multicenter, escalating dose study evaluating the pharmacokinetics and pharmacodynamics of dexmedetomidine in pediatric subjects. The study population consists of initially intubated and mechanically ventilated pediatric subjects, ages ≥2 through <17 years old, that require sedation in an intensive care setting for a minimum of 6 hours. Subjects will be divided into two groups based on age: Group I will consist of subjects ages ≥2 through <6 years old and Group II subjects age ≥6 through <17 years old. Within each group there will be four escalating dosing levels. Both groups can enroll simultaneously; however within each group, the next dose level cannot begin to enroll until all subjects have completed the previous dose level and the Data Safety Monitoring Board (DSMB) has approved enrollment to the next level. The level of sedation will be assessed using the Ramsay Sedation Scale (RSS). Based on these scores, and clinical judgment, additional sedation with midazolam will be administered according to the label. Pain will be assessed using the Faces, Legs, Arms, Cry \& Consolability (FLACC) scale. Venous blood samples for pharmacokinetic analysis will be obtained at designated times. The pharmacodynamic and safety measures that will be monitored and the pharmacodynamic impact of dexmedetomidine on tracheal extubation will also be explored if subject is extubated within 24 hours.

Conditions: Intubated and Mechanically Ventilated Pediatric Subjects
Being tested: Dexmedetomidine, midazolam; fentanyl
Keywords: Pharmacokinetics, Pharmacodynamics, Escalating dose, Dexmedotimidine, Intubated, Mechanically ventilated, Pediatrics

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Dexmedetomidine, midazolam; fentanylDrug
Dexmedetomidine for sedation; midazolam for rescue sedation according to label; fentanyl for rescue pain according to the label

Study groups in NCT00652028
Study group	Role	What they receive
Group 1	Other	Dose level 1 Receives: Drug: Dexmedetomidine, midazolam; fentanyl
Group 2	Other	Dose level 2 Receives: Drug: Dexmedetomidine, midazolam; fentanyl
Group 3	Other	Dose level 3 Receives: Drug: Dexmedetomidine, midazolam; fentanyl
Group 4	Other	Dose level 4 Receives: Drug: Dexmedetomidine, midazolam; fentanyl

What is being measured

The primary outcome is the main question the study is designed to answer.

Area Under the Concentration-time Curve From Time Zero to the Time of the Last Measurable Concentration (AUC0-t)
Area under the concentration-time curve from time zero to the time of the last measurable concentration (AUC0-t) for Dexmedetomidine
Measured: ≤30 min prior to start of loading dose (LD); 5 min before finishing LD; 0.5,1,2 & 4-6 hrs after start of maintenance infusion (MI); 30 min prior to end of MI (within 24 hrs of start of MI); 10 min after end of MI and 0.5,1,2,4 & 10 hrs after end of MI.
Area Under the Concentration-time Curve From Time Zero to the Time Infinity (AUC0-∞)
Area under the concentration-time curve from time zero to the time infinity (AUC0-∞) for Dexmedetomidine
Measured: ≤30 min prior to start of the loading dose (LD); 5 min before finishing the LD; 0.5,1,2&4 to 6 hrs after start of maintenance infusion (MI); 30 min prior to end of MI (24 hrs of start of MI); 10 min after end of MI and 0.5,1,2,4&10 hrs after end of MI.
Observed Peak Plasma Concentration
Observed peak plasma concentration (Cmax) for Dexmedetomidine
Measured: ≤30 min prior to start of the loading dose (LD); 5 min before finishing the LD; 0.5,1,2&4 to 6 hrs after start of maintenance infusion (MI); 30 min prior to end of MI (24 hrs of start of MI); 10 min after end of MI and 0.5,1,2,4&10 hrs after end of MI.
Terminal Elimination Half-life (t1/2)
Terminal elimination half-life (t1/2) for Dexmedetomidine
Measured: ≤30 min prior to start of loading dose (LD); 5 min before finishing LD; 0.5,1,2 & 4-6 hrs after start of maintenance infusion (MI); 30 min prior to end of MI (within 24 hrs of start of MI); 10 min after end of MI and 0.5,1,2,4 & 10 hrs after end of MI.
Plasma Concentration at Steady State (Css)
Plasma concentration at steady state (Css) for Dexmedetomidine
Measured: ≤30 min prior to start of loading dose (LD); 5 min before finishing LD; 0.5,1,2 & 4-6 hrs after start of maintenance infusion (MI); 30 min prior to end of MI (within 24 hrs of start of MI); 10 min after end of MI and 0.5,1,2,4 & 10 hrs after end of MI.
Volume of Steady State Distribution (Vss)
Volume of steady state distribution (Vss) for Dexmedetomidine
Measured: ≤30 min prior to start of loading dose (LD); 5 min before finishing LD; 0.5,1,2 & 4-6 hrs after start of maintenance infusion (MI); 30 min prior to end of MI (within 24 hrs of start of MI); 10 min after end of MI and 0.5,1,2,4 & 10 hrs after end of MI.
Clearance (CL)
Clearance (CL) for Dexmedetomidine
Measured: ≤30 min prior to start of loading dose (LD); 5 min before finishing LD; 0.5,1,2 & 4-6 hrs after start of maintenance infusion (MI); 30 min prior to end of MI (within 24 hrs of start of MI); 10 min after end of MI and 0.5,1,2,4 & 10 hrs after end of MI.
Level of Sedation Based on Average Ramsay Sedation Scale (RSS) Score
RSS Score range from 1 to 6:
1. Patient is anxious and agitated or restless, or both.
2. Patient is cooperative, orientated and tranquil.
3. Patient responds to command only.
4. Patient exhibits brisk response to light glabellar (between the eyebrows) tap or loud auditory stimulus.
5. Patient exhibits a sluggish response to light glabellar tap or loud auditory stimulus.
6. Patient exhibits no response to stimulus.
Measured: Prior to loading (Baseline), 5 and 10 min during the load, at start of maintenance infusion and every 15 min for 1 hour, hourly during the maintenance period, before and within 5 min after midazolam or fentanyl dose during the dexmedetomidine infusion.
Number of Subjects Who Received Rescue Medication for Sedation (Midazolam) and Analgesics (Fentanyl)
Number of subjects who received rescue medication for Sedation (Midazolam) and analgesics (Fentanyl) while intubated during Treatment Period
Measured: During the treatment period (Approximately 24 hours)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Nov 2008Apr 2010

First posted3 Apr 2008 (estimated)
Study startNov 2008
Primary completionApr 2010
Study completionApr 2010

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Intubated and Mechanically Ventilated Pediatric SubjectsStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)
Enrolment: 69 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00652028
Sponsor's protocol ID: DEX-08-01
Status last verified: Aug 2015
First submitted: 1 Apr 2008
Last updated: 13 Apr 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes