Open-Label, Safety Study Evaluating the Use of Dexmedetomidine in Pediatric Subjects Undergoing Procedure-Type Sedation

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hospira, Inc.
ClinicalTrials.gov Identifier:
NCT01519167
First received: January 24, 2012
Last updated: August 7, 2015
Last verified: August 2015
  Purpose

The objective of this study is to evaluate the safety of dexmedetomidine in a pediatric population requiring non-intubated, spontaneous breathing, moderate to deep sedation (NI-MDS) for elective diagnostic or therapeutic procedures, expected to take more than 30 minutes.


Condition Intervention Phase
Ultrasound
CT Scans
MRIs
Drug: Dexmedetomidine
Drug: Midazolam
Drug: Fentanyl
Phase 4

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase IV, Open-Label, Safety Study Evaluating the Use of Dexmedetomidine in Pediatric Subjects Undergoing Procedure-Type Sedation

Resource links provided by NLM:


Further study details as provided by Hospira, Inc.:

Primary Outcome Measures:
  • Number of Subjects Who Had Success in Sedation [ Time Frame: From baseline to end of post-treatment period (approximately 24 hours) ] [ Designated as safety issue: Yes ]

    Success in sedation was defined by a combined endpoint which was the combination of the following:

    1. Subject had adequate level of sedation (University of Michigan Sedation Scale [UMSS] score between 1 to 3 [minimally sedated to deeply sedated] or Neonatal Pain, Agitation and Sedation Scale [N-PASS] score between -5 to -2 [Light sedation]) at least 80% of the time the subject was given the study drug.
    2. Subject had successfully completed the procedure without a need for rescue sedation (Midazolam).
    3. Subject had undergone the procedure without artificial ventilation or intervention to restore baseline or normal hemodynamic status


Secondary Outcome Measures:
  • Number of Subjects Not Receiving Rescue Midazolam [ Time Frame: During the treatment period, up to approximately 24 hours ] [ Designated as safety issue: Yes ]
    Number of subjects who did not receive any rescue midazolam for sedation during the study drug infusion.

  • Number of Subjects Who Have Undergone Procedures Without Artificial Ventilation or Intervention [ Time Frame: During the treatment period, up to approximately 24 hours ] [ Designated as safety issue: Yes ]
  • Number of Subjects Who Were Adequately Sedated at Least 80% of Time [ Time Frame: During the treatment period, up to approximately 24 hours ] [ Designated as safety issue: Yes ]
    Subjects who are adequately sedated (UMSS score of 1 to 3 or NPASS score of -5 to -2) at least 80% of the time sedated with the study drug

  • Time to First Dose of Rescue Midazolam From Start of Dexmedetomidine Infusion [ Time Frame: During the treatment period, up to approximately 24 hours ] [ Designated as safety issue: Yes ]
    Kaplan-Meier estimates of time in minutes to first dose of rescue midazolam from onset of study drug infusion

  • Frequency of Midazolam Required for Sedation [ Time Frame: During the treatment period, up to approximately 24 hours ] [ Designated as safety issue: Yes ]
    Frequency of rescue sedation (midazolam) required to maintain a subject within the target sedation range (UMSS score greater than 1 or N-PASS score less than -2).

  • Frequency of Fentanyl Use for Analgesia [ Time Frame: During the treatment period, up to approximately 24 hours ] [ Designated as safety issue: Yes ]
    Frequency of rescue analgesia (fentanyl) required from the start of IV sedation to completion of the procedure.

  • Total Amount of Rescue Sedation (Midazolam) [ Time Frame: During the treatment period, up to approximately 24 hours ] [ Designated as safety issue: Yes ]
    Total amount of rescue sedation (midazolam) required from the start of IV sedation to completion of the procedure

  • Total Amount of Rescue Analgesia (Fentanyl) [ Time Frame: During the treatment period, up to approximately 24 hours ] [ Designated as safety issue: Yes ]
    Total amount of rescue analgesia (fentanyl) required from the start of IV sedation to completion of the procedure

  • Number of Subjects Converted to Alternative Sedation or Anesthetic Therapy Due to Failure of Treatment of Study Drug and Rescue Medication [ Time Frame: During the treatment period, up to approximately 24 hours ] [ Designated as safety issue: Yes ]

Enrollment: 91
Study Start Date: October 2012
Study Completion Date: January 2014
Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dexmedetomidine Drug: Dexmedetomidine
0.1 - 1.0 mcg/kg/hr IV
Drug: Midazolam
0.025 - 2 mg/kg IV
Drug: Fentanyl
0.5 - 3 mcg/kg IV

Detailed Description:

This study was designed to evaluate the safety of a continuous infusion of dexmedetomidine (1 mcg/kg loading dose with 0.6 mcg/kg/hr initial maintenance dose and titrated between 0.2-1.0 mcg/kg/hr) administered to subjects requiring non-intubated, spontaneous breathing, moderate to deep sedation (NI-MDS) for elective diagnostic or therapeutic procedures that are expected to take more than 30 minutes.

  Eligibility

Ages Eligible for Study:   28 Weeks to 16 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Subject is ≥28 weeks gestational age and <17 years of age.

    - Preterm subjects ≥28 weeks through <38 weeks, gestational age; (Note: Gestational age will be calculated as the time elapsed between the first day of the last menstrual period to the day of enrollment. If pregnancy was achieved using assisted reproductive technology, gestational age will be calculated by adding 2 weeks to the gestational age as calculated above.)

  2. Subject is American Society of Anesthesiologists (ASA) Physical Status I, II or III.
  3. Subject requires non-intubated, spontaneous breathing, moderate to deep sedation (NI-MDS) in an operating or procedure room with an an intensivist, anesthesiologist or dental anesthesiologist in attendance.
  4. Scheduled for an elective procedure that falls into one of the following three populations:

    • Non-invasive diagnostic/therapeutic procedures (NIDTP): including ultrasound (US), computed tomography (CT) scans, magnetic resonance imaging (MRI), cardiac catheterization, transthoracic echocardiogram (TTE);
    • Minimally invasive diagnostic/therapeutic procedures (MIDTP): including minimally invasive procedures performed under US or CT guidance (e.g. US or CT-guided solid organ biopsy), and routine myocardial biopsies in cardiac transplant recipients;
    • Surgical procedures: including small surgical procedures (e.g. excisions, biopsies) and dental procedures (e.g. extractions, pulpectomy, pediatric rehabilitation dental procedures, filings and crowns).
  5. Duration of the procedure is expected to take at least 30 minutes to complete.
  6. If female, subject is non-lactating and is either:

    1. Not of childbearing potential, defined as pre-menarche, or surgically sterile due to bilateral tubal ligation, bilateral oophorectomy or hysterectomy.
    2. Of childbearing potential but is not pregnant at time of baseline and is practicing one of the following methods of birth control: oral or parenteral contraceptives, double-barrier method, vasectomized partner, or abstinence from sexual intercourse.
  7. Subject's parent(s) or legally acceptable representative(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.

Exclusion Criteria:

  1. Subjects weight at the time of screening is less than 1000 g.
  2. Subject has received general anesthesia within 7 days prior to study drug administration.
  3. Subject has participated in an experimental/investigational drug study within 30 days prior to study drug administration.
  4. Subject has been exposed to dexmedetomidine within 48 hours prior to study drug administration.
  5. Subject that has been previously enrolled in this study (DEX-10-16).
  6. Subject requires endotracheal intubation or laryngeal mask airway (LMA).
  7. Subject is with neurological conditions that in the opinion of the Investigator will preclude reliable assessment of sedation scoring. Examples include, but are not limited to the following: cerebral palsy, autism, severe mental retardation, etc.
  8. Subject has central nervous system (CNS) disease with an anticipated potential for increased intracranial pressure, an uncontrolled seizure disorder and/or known psychiatric illness that could confound a normal response to sedative treatment.
  9. Subject requires epidural or spinal anesthesia.
  10. Subject has received treatment with an alpha-2 agonist or antagonist within 14 days prior to study drug administration.
  11. Subject has a known allergy to dexmedetomidine, midazolam or fentanyl.
  12. Subject is requiring cardiac catheterization for the purpose of conducting an electrophysiology (EP) evaluation or percutaneous intervention (i.e. angioplasty).
  13. Subject for whom opiates, benzodiazepines, dexmedetomidine or other alpha-2 agonists are contraindicated.
  14. Subject has received an IV opioid within one hour, or oral/intramuscular (PO/IM) opioid within four hours, prior to the start of study drug administration.
  15. Subject has received any pre-induction medication (ie, ketamine, chloral hydrate, benzodiazepines) within 4 hours prior to the start of study drug administration.
  16. Subject has acute myocardial infarction recently diagnosed by confirmatory laboratory findings within 6 weeks of screening.
  17. Subject has moderate to severe sleep apnea syndrome.
  18. Subject has oxygen saturation (SpO2) ≤90% at screening or baseline, except for patients with known cyanotic heart disease undergoing cardiac catheterization.
  19. Subject has bradycardia immediately before dosing, according to respective age group.

    • ≥28 weeks to <1 month: Heart Rate (HR) <120 beats per minute (bpm)
    • 1 month to <3 months: HR <100 bpm
    • 3 months to <6 months: HR <90 bpm
    • 6 months to <1 year: HR <80 bpm
    • 1 year to <2 years: HR <70 bpm
    • 2 years to <6 years: HR <60 bpm
    • 6 years to <12 years: HR <55 bpm
    • 12 years to 17 years: HR <50 bpm;

    Note: Subject can be reassessed after 5 minutes

  20. Subject has hypotension immediately before dosing, according to respective age group.

    • ≥28 weeks to <1 month: <60 mmHg (systolic blood pressure [SBP])
    • 1 month to <12 months: <70 mmHg (SBP)
    • 1 year to <10 years: <70 + (2 X age in years) mmHg (SBP)
    • 10 years to 17 years: <90 mmHg (SBP);

    Note: Subject can be reassessed after 5 minutes

  21. Subject has a presence of second-degree or third-degree heart block at screening or baseline. The presence of a temporary or permanent pacemaker will waive this exclusion criterion.
  22. Subject has acute febrile illness, with a temperature (core or tympanic) ≥38.0°C.
  23. Subject has any other condition or factor which, in the Investigator's opinion, might increase the risk to the subject.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01519167

Locations
United States, Arkansas
Little Rock, Arkansas, United States, 72202
United States, California
Anaheim, California, United States, 92801
Stanford, California, United States, 94305
United States, Florida
Miami, Florida, United States, 33136
United States, North Carolina
Durham, North Carolina, United States, 27710
United States, Pennsylvania
Pittsburgh, Pennsylvania, United States, 15224
United States, Tennessee
Nashville, Tennessee, United States, 37232-9070
United States, Texas
Dallas, Texas, United States, 75235
United States, Utah
Sandy, Utah, United States, 84096
Puerto Rico
San Juan, Puerto Rico, 00936-5067
San Juan, Puerto Rico, 00936
Sponsors and Collaborators
Hospira, Inc.
  More Information

No publications provided

Responsible Party: Hospira, Inc.
ClinicalTrials.gov Identifier: NCT01519167     History of Changes
Other Study ID Numbers: DEX-10-16
Study First Received: January 24, 2012
Results First Received: May 5, 2015
Last Updated: August 7, 2015
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Dexmedetomidine
Adrenergic Agents
Adrenergic Agonists
Adrenergic alpha-2 Receptor Agonists
Adrenergic alpha-Agonists
Analgesics
Analgesics, Non-Narcotic
Central Nervous System Agents
Central Nervous System Depressants
Hypnotics and Sedatives
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Sensory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 27, 2015