Trial Outcomes & Findings for Open-Label, Safety Study Evaluating the Use of Dexmedetomidine in Pediatric Subjects Undergoing Procedure-Type Sedation (NCT NCT01519167)

NCT ID: NCT01519167

Last Updated: 2017-03-20

Results Overview

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

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 91 participants
• Primary outcome timeframe: From baseline to end of post-treatment period (approximately 24 hours)
• Results posted on: 2017-03-20

Participant Flow

The number of subjects enrolled was 91, of that 90 subjects received study drug. The remaining 1 subject not treated due to subject being a screen failure.

Participant milestones

Measure	Dose Level 1 Dexmedetomidine Loading dose 0.1 mcg/kg and Maintenance dose 0.1 mcg/kg/hr	Dose Level 2 Dexmedetomidine Loading dose 1 mcg/kg and Maintenance dose 0.6 mcg/kg/hr
Overall Study STARTED	1	89
Overall Study COMPLETED	1	81
Overall Study NOT COMPLETED	0	8

Reasons for withdrawal

Measure	Dose Level 1 Dexmedetomidine Loading dose 0.1 mcg/kg and Maintenance dose 0.1 mcg/kg/hr	Dose Level 2 Dexmedetomidine Loading dose 1 mcg/kg and Maintenance dose 0.6 mcg/kg/hr
Overall Study Diagnostic/TherapeuticProcedureCompleted	0	3
Overall Study Adverse Event	0	1
Overall Study Lack of Efficacy	0	1
Overall Study Medical condition changes&deep sedation	0	2
Overall Study Physician Decision	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Dose Level 1 n=1 Participants Dexmedetomidine Loading dose 0.1 mcg/kg and Maintenance dose 0.1 mcg/kg/hr	Dose Level 2 n=89 Participants Dexmedetomidine Loading dose 1 mcg/kg and Maintenance dose 0.6 mcg/kg/hr	Total n=90 Participants Total of all reporting groups
Age, Continuous	0.1 years n=5 Participants	7.97 years n=7 Participants	7.89 years n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	41 Participants n=7 Participants	41 Participants n=5 Participants
Sex: Female, Male Male	1 Participants n=5 Participants	48 Participants n=7 Participants	49 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	23 Participants n=7 Participants	23 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	1 Participants n=5 Participants	66 Participants n=7 Participants	67 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	22 Participants n=7 Participants	23 Participants n=5 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants	60 Participants n=7 Participants	60 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	6 Participants n=7 Participants	6 Participants n=5 Participants

PRIMARY outcome

Timeframe: From baseline to end of post-treatment period (approximately 24 hours)

Population: Efficacy Evaluable Population (Participants who received study drug infusion for at least 30 minutes and had no major protocol deviations)

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

Outcome measures

Measure	Dose Level 1 n=1 Participants Dexmedetomidine Loading dose 0.1 mcg/kg and Maintenance dose 0.1 mcg/kg/hr	Dose Level 2 n=77 Participants Dexmedetomidine Loading dose 1 mcg/kg and Maintenance dose 0.6 mcg/kg/hr
Number of Subjects Who Had Success in Sedation NIDTP (n=1, 40)	0 participants	2 participants
Number of Subjects Who Had Success in Sedation MIDTP (n=0, 25)	0 participants	0 participants
Number of Subjects Who Had Success in Sedation Surgical procedures (n=0, 12)	0 participants	0 participants

SECONDARY outcome

Timeframe: During the treatment period, up to approximately 24 hours

Population: Efficacy Evaluable Population (Participants who received study drug infusion for at least 30 minutes and had no major protocol deviations)

Number of subjects who did not receive any rescue midazolam for sedation during the study drug infusion.

Outcome measures

Measure	Dose Level 1 n=1 Participants Dexmedetomidine Loading dose 0.1 mcg/kg and Maintenance dose 0.1 mcg/kg/hr	Dose Level 2 n=77 Participants Dexmedetomidine Loading dose 1 mcg/kg and Maintenance dose 0.6 mcg/kg/hr
Number of Subjects Not Receiving Rescue Midazolam Surgical procedures (n=0, 12)	0 participants	1 participants
Number of Subjects Not Receiving Rescue Midazolam NIDTP (n=1, 40)	1 participants	12 participants
Number of Subjects Not Receiving Rescue Midazolam MIDTP (n=0, 25)	0 participants	5 participants

SECONDARY outcome

Timeframe: During the treatment period, up to approximately 24 hours

Population: Efficacy Evaluable Population (Participants who received study drug infusion for at least 30 minutes and had no major protocol deviations)

Outcome measures

Measure	Dose Level 1 n=1 Participants Dexmedetomidine Loading dose 0.1 mcg/kg and Maintenance dose 0.1 mcg/kg/hr	Dose Level 2 n=77 Participants Dexmedetomidine Loading dose 1 mcg/kg and Maintenance dose 0.6 mcg/kg/hr
Number of Subjects Who Have Undergone Procedures Without Artificial Ventilation or Intervention NIDTP (n=1, 40)	1 participants	37 participants
Number of Subjects Who Have Undergone Procedures Without Artificial Ventilation or Intervention MIDTP (n=0, 25)	0 participants	19 participants
Number of Subjects Who Have Undergone Procedures Without Artificial Ventilation or Intervention Surgical procedures (n=0, 12)	0 participants	12 participants

SECONDARY outcome

Timeframe: During the treatment period, up to approximately 24 hours

Population: Efficacy Evaluable Population (Participants who received study drug infusion for at least 30 minutes and had no major protocol deviations)

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

Outcome measures

Measure	Dose Level 1 n=1 Participants Dexmedetomidine Loading dose 0.1 mcg/kg and Maintenance dose 0.1 mcg/kg/hr	Dose Level 2 n=77 Participants Dexmedetomidine Loading dose 1 mcg/kg and Maintenance dose 0.6 mcg/kg/hr
Number of Subjects Who Were Adequately Sedated at Least 80% of Time NIDTP (n=1, 40)	0 participants	21 participants
Number of Subjects Who Were Adequately Sedated at Least 80% of Time MIDTP (n=0, 25)	0 participants	7 participants
Number of Subjects Who Were Adequately Sedated at Least 80% of Time Surgical procedures (n=0, 12)	0 participants	2 participants

SECONDARY outcome

Timeframe: During the treatment period, up to approximately 24 hours

Population: Efficacy Evaluable Population (Participants who received study drug infusion for at least 30 minutes and had no major protocol deviations)

Kaplan-Meier estimates of time in minutes to first dose of rescue midazolam from onset of study drug infusion

Outcome measures

Measure	Dose Level 1 n=1 Participants Dexmedetomidine Loading dose 0.1 mcg/kg and Maintenance dose 0.1 mcg/kg/hr	Dose Level 2 n=77 Participants Dexmedetomidine Loading dose 1 mcg/kg and Maintenance dose 0.6 mcg/kg/hr
Time to First Dose of Rescue Midazolam From Start of Dexmedetomidine Infusion NIDTP (n=1, 40)	NA Hours There was one subject in this group (n=1) and the subject did not receive rescue midazolam.	23.5 Hours Interval 16.0 to 28.0
Time to First Dose of Rescue Midazolam From Start of Dexmedetomidine Infusion MIDTP (n=0, 25)	NA Hours No subjects were in the MIDTP group	20.00 Hours Interval 17.0 to 34.0
Time to First Dose of Rescue Midazolam From Start of Dexmedetomidine Infusion Surgical procedures (n=0, 12)	NA Hours No subjects were in the surgical procedures group	20.00 Hours Interval 15.0 to 25.0

SECONDARY outcome

Timeframe: During the treatment period, up to approximately 24 hours

Population: Number of subjects who received any amount (mg) of rescue midazolam for sedation in efficacy evaluable population.

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).

Outcome measures

Measure	Dose Level 1 Dexmedetomidine Loading dose 0.1 mcg/kg and Maintenance dose 0.1 mcg/kg/hr	Dose Level 2 n=59 Participants Dexmedetomidine Loading dose 1 mcg/kg and Maintenance dose 0.6 mcg/kg/hr
Frequency of Midazolam Required for Sedation NIDTP (n=0, 28)	—	2 Occurrence Interval 1.0 to 4.0
Frequency of Midazolam Required for Sedation MIDTP (n=0, 20)	—	1 Occurrence Interval 1.0 to 2.0
Frequency of Midazolam Required for Sedation Surgical procedures (n=0, 11)	—	1 Occurrence Interval 1.0 to 2.0

SECONDARY outcome

Timeframe: During the treatment period, up to approximately 24 hours

Population: Number of subjects who received any amount (mg) of rescue fentanyl for analgesia in efficacy evaluable population.

Frequency of rescue analgesia (fentanyl) required from the start of IV sedation to completion of the procedure.

Outcome measures

Measure	Dose Level 1 Dexmedetomidine Loading dose 0.1 mcg/kg and Maintenance dose 0.1 mcg/kg/hr	Dose Level 2 n=40 Participants Dexmedetomidine Loading dose 1 mcg/kg and Maintenance dose 0.6 mcg/kg/hr
Frequency of Fentanyl Use for Analgesia NIDTP (n=0, 6)	—	1 Occurrence Interval 1.0 to 3.0
Frequency of Fentanyl Use for Analgesia MIDTP (n=0, 22)	—	1 Occurrence Interval 1.0 to 5.0
Frequency of Fentanyl Use for Analgesia Surgical procedures (n=0, 12)	—	2.50 Occurrence Interval 1.0 to 5.0

SECONDARY outcome

Timeframe: During the treatment period, up to approximately 24 hours

Population: Number of subjects who received any amount (mg) of rescue midazolam for sedation in efficacy evaluable population.

Total amount of rescue sedation (midazolam) required from the start of IV sedation to completion of the procedure

Outcome measures

Measure	Dose Level 1 Dexmedetomidine Loading dose 0.1 mcg/kg and Maintenance dose 0.1 mcg/kg/hr	Dose Level 2 n=59 Participants Dexmedetomidine Loading dose 1 mcg/kg and Maintenance dose 0.6 mcg/kg/hr
Total Amount of Rescue Sedation (Midazolam) NIDTP (n=0, 28)	—	2.62 milligram Standard Deviation 1.611
Total Amount of Rescue Sedation (Midazolam) MIDTP (n=0, 20)	—	1.70 milligram Standard Deviation 0.767
Total Amount of Rescue Sedation (Midazolam) Surgical procedures (n=0, 11)	—	2.45 milligram Standard Deviation 0.907

SECONDARY outcome

Timeframe: During the treatment period, up to approximately 24 hours

Population: Number of subjects who received any amount (mg) of rescue fentanyl for analgesia in efficacy evaluable population.

Total amount of rescue analgesia (fentanyl) required from the start of IV sedation to completion of the procedure

Outcome measures

Measure	Dose Level 1 Dexmedetomidine Loading dose 0.1 mcg/kg and Maintenance dose 0.1 mcg/kg/hr	Dose Level 2 n=40 Participants Dexmedetomidine Loading dose 1 mcg/kg and Maintenance dose 0.6 mcg/kg/hr
Total Amount of Rescue Analgesia (Fentanyl) NIDTP (n=0, 6)	—	10.83 microgram Standard Deviation 8.010
Total Amount of Rescue Analgesia (Fentanyl) MIDTP (n=0, 22)	—	61.86 microgram Standard Deviation 65.740
Total Amount of Rescue Analgesia (Fentanyl) Surgical procedures (n=0, 12)	—	104.83 microgram Standard Deviation 72.007

SECONDARY outcome

Timeframe: During the treatment period, up to approximately 24 hours

Population: Efficacy Evaluable Population (Participants who received study drug infusion for at least 30 minutes and had no major protocol deviations)

Outcome measures

Measure	Dose Level 1 n=1 Participants Dexmedetomidine Loading dose 0.1 mcg/kg and Maintenance dose 0.1 mcg/kg/hr	Dose Level 2 n=77 Participants Dexmedetomidine Loading dose 1 mcg/kg and Maintenance dose 0.6 mcg/kg/hr
Number of Subjects Converted to Alternative Sedation or Anesthetic Therapy Due to Failure of Treatment of Study Drug and Rescue Medication MIDTP (n=0, 25)	0 Participants	0 Participants
Number of Subjects Converted to Alternative Sedation or Anesthetic Therapy Due to Failure of Treatment of Study Drug and Rescue Medication NIDTP (n=1, 40)	0 Participants	0 Participants
Number of Subjects Converted to Alternative Sedation or Anesthetic Therapy Due to Failure of Treatment of Study Drug and Rescue Medication Surgical procedures (n=0, 12)	0 Participants	2 Participants

Adverse Events

Dose Level 1

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Dose Level 2

Serious events: 1 serious events

Other events: 66 other events

Deaths: 0 deaths

Serious adverse events

Measure	Dose Level 1 n=1 participants at risk Dexmedetomidine Loading dose 0.1 mcg/kg and Maintenance dose 0.1 mcg/kg/hr	Dose Level 2 n=89 participants at risk Dexmedetomidine Loading dose 1 mcg/kg and Maintenance dose 0.6 mcg/kg/hr
Nervous system disorders Syncope	0.00% 0/1 • Non-serious adverse events from start of study drug administration until 24(±12) hours following study drug discontinuation. Reported serious adverse events from the time the subject signed informed consent until 30 days after study drug discontinuation.	1.1% 1/89 • Number of events 1 • Non-serious adverse events from start of study drug administration until 24(±12) hours following study drug discontinuation. Reported serious adverse events from the time the subject signed informed consent until 30 days after study drug discontinuation.

Other adverse events

Measure	Dose Level 1 n=1 participants at risk Dexmedetomidine Loading dose 0.1 mcg/kg and Maintenance dose 0.1 mcg/kg/hr	Dose Level 2 n=89 participants at risk Dexmedetomidine Loading dose 1 mcg/kg and Maintenance dose 0.6 mcg/kg/hr
Cardiac disorders Bradycardia	0.00% 0/1 • Non-serious adverse events from start of study drug administration until 24(±12) hours following study drug discontinuation. Reported serious adverse events from the time the subject signed informed consent until 30 days after study drug discontinuation.	4.5% 4/89 • Non-serious adverse events from start of study drug administration until 24(±12) hours following study drug discontinuation. Reported serious adverse events from the time the subject signed informed consent until 30 days after study drug discontinuation.
Cardiac disorders Tachycardia	0.00% 0/1 • Non-serious adverse events from start of study drug administration until 24(±12) hours following study drug discontinuation. Reported serious adverse events from the time the subject signed informed consent until 30 days after study drug discontinuation.	1.1% 1/89 • Non-serious adverse events from start of study drug administration until 24(±12) hours following study drug discontinuation. Reported serious adverse events from the time the subject signed informed consent until 30 days after study drug discontinuation.
Gastrointestinal disorders Diarrhoea	0.00% 0/1 • Non-serious adverse events from start of study drug administration until 24(±12) hours following study drug discontinuation. Reported serious adverse events from the time the subject signed informed consent until 30 days after study drug discontinuation.	1.1% 1/89 • Non-serious adverse events from start of study drug administration until 24(±12) hours following study drug discontinuation. Reported serious adverse events from the time the subject signed informed consent until 30 days after study drug discontinuation.
Gastrointestinal disorders Nausea	0.00% 0/1 • Non-serious adverse events from start of study drug administration until 24(±12) hours following study drug discontinuation. Reported serious adverse events from the time the subject signed informed consent until 30 days after study drug discontinuation.	2.2% 2/89 • Non-serious adverse events from start of study drug administration until 24(±12) hours following study drug discontinuation. Reported serious adverse events from the time the subject signed informed consent until 30 days after study drug discontinuation.
Gastrointestinal disorders Vomiting	0.00% 0/1 • Non-serious adverse events from start of study drug administration until 24(±12) hours following study drug discontinuation. Reported serious adverse events from the time the subject signed informed consent until 30 days after study drug discontinuation.	2.2% 2/89 • Non-serious adverse events from start of study drug administration until 24(±12) hours following study drug discontinuation. Reported serious adverse events from the time the subject signed informed consent until 30 days after study drug discontinuation.
Investigations Blood pressure diastolic decreased	0.00% 0/1 • Non-serious adverse events from start of study drug administration until 24(±12) hours following study drug discontinuation. Reported serious adverse events from the time the subject signed informed consent until 30 days after study drug discontinuation.	2.2% 2/89 • Non-serious adverse events from start of study drug administration until 24(±12) hours following study drug discontinuation. Reported serious adverse events from the time the subject signed informed consent until 30 days after study drug discontinuation.
Investigations Blood pressure systolic decreased	0.00% 0/1 • Non-serious adverse events from start of study drug administration until 24(±12) hours following study drug discontinuation. Reported serious adverse events from the time the subject signed informed consent until 30 days after study drug discontinuation.	3.4% 3/89 • Non-serious adverse events from start of study drug administration until 24(±12) hours following study drug discontinuation. Reported serious adverse events from the time the subject signed informed consent until 30 days after study drug discontinuation.
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/1 • Non-serious adverse events from start of study drug administration until 24(±12) hours following study drug discontinuation. Reported serious adverse events from the time the subject signed informed consent until 30 days after study drug discontinuation.	1.1% 1/89 • Non-serious adverse events from start of study drug administration until 24(±12) hours following study drug discontinuation. Reported serious adverse events from the time the subject signed informed consent until 30 days after study drug discontinuation.
Metabolism and nutrition disorders Hyperkalaemia	0.00% 0/1 • Non-serious adverse events from start of study drug administration until 24(±12) hours following study drug discontinuation. Reported serious adverse events from the time the subject signed informed consent until 30 days after study drug discontinuation.	1.1% 1/89 • Non-serious adverse events from start of study drug administration until 24(±12) hours following study drug discontinuation. Reported serious adverse events from the time the subject signed informed consent until 30 days after study drug discontinuation.
Nervous system disorders Headache	0.00% 0/1 • Non-serious adverse events from start of study drug administration until 24(±12) hours following study drug discontinuation. Reported serious adverse events from the time the subject signed informed consent until 30 days after study drug discontinuation.	3.4% 3/89 • Non-serious adverse events from start of study drug administration until 24(±12) hours following study drug discontinuation. Reported serious adverse events from the time the subject signed informed consent until 30 days after study drug discontinuation.
Nervous system disorders Somnolence	0.00% 0/1 • Non-serious adverse events from start of study drug administration until 24(±12) hours following study drug discontinuation. Reported serious adverse events from the time the subject signed informed consent until 30 days after study drug discontinuation.	1.1% 1/89 • Non-serious adverse events from start of study drug administration until 24(±12) hours following study drug discontinuation. Reported serious adverse events from the time the subject signed informed consent until 30 days after study drug discontinuation.
Psychiatric disorders Agitation	0.00% 0/1 • Non-serious adverse events from start of study drug administration until 24(±12) hours following study drug discontinuation. Reported serious adverse events from the time the subject signed informed consent until 30 days after study drug discontinuation.	1.1% 1/89 • Non-serious adverse events from start of study drug administration until 24(±12) hours following study drug discontinuation. Reported serious adverse events from the time the subject signed informed consent until 30 days after study drug discontinuation.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/1 • Non-serious adverse events from start of study drug administration until 24(±12) hours following study drug discontinuation. Reported serious adverse events from the time the subject signed informed consent until 30 days after study drug discontinuation.	2.2% 2/89 • Non-serious adverse events from start of study drug administration until 24(±12) hours following study drug discontinuation. Reported serious adverse events from the time the subject signed informed consent until 30 days after study drug discontinuation.
Respiratory, thoracic and mediastinal disorders Respiratory depression	100.0% 1/1 • Non-serious adverse events from start of study drug administration until 24(±12) hours following study drug discontinuation. Reported serious adverse events from the time the subject signed informed consent until 30 days after study drug discontinuation.	59.6% 53/89 • Non-serious adverse events from start of study drug administration until 24(±12) hours following study drug discontinuation. Reported serious adverse events from the time the subject signed informed consent until 30 days after study drug discontinuation.
Skin and subcutaneous tissue disorders Rash	0.00% 0/1 • Non-serious adverse events from start of study drug administration until 24(±12) hours following study drug discontinuation. Reported serious adverse events from the time the subject signed informed consent until 30 days after study drug discontinuation.	1.1% 1/89 • Non-serious adverse events from start of study drug administration until 24(±12) hours following study drug discontinuation. Reported serious adverse events from the time the subject signed informed consent until 30 days after study drug discontinuation.
Vascular disorders Hypertension	0.00% 0/1 • Non-serious adverse events from start of study drug administration until 24(±12) hours following study drug discontinuation. Reported serious adverse events from the time the subject signed informed consent until 30 days after study drug discontinuation.	2.2% 2/89 • Non-serious adverse events from start of study drug administration until 24(±12) hours following study drug discontinuation. Reported serious adverse events from the time the subject signed informed consent until 30 days after study drug discontinuation.
Vascular disorders Hypotension	0.00% 0/1 • Non-serious adverse events from start of study drug administration until 24(±12) hours following study drug discontinuation. Reported serious adverse events from the time the subject signed informed consent until 30 days after study drug discontinuation.	41.6% 37/89 • Non-serious adverse events from start of study drug administration until 24(±12) hours following study drug discontinuation. Reported serious adverse events from the time the subject signed informed consent until 30 days after study drug discontinuation.

Additional Information

Marcelo Garcia de Rocha MD, Global Medical Director

Hospira

Phone: 224-212-4424

Email: marcelo.rocha@hospira.com

Results disclosure agreements

• Principal investigator is a sponsor employee The Investigator may not submit the results of the study for publication without the prior written consent of Hospira.
• Publication restrictions are in place

Restriction type: OTHER