Alternative Sedation During Bronchoscopy (DEX)

• ClinicalTrials.gov Identifier: NCT01158820
• Recruitment Status: Completed
• First Posted: July 8, 2010
• Results First Posted: October 31, 2018
• Last Update Posted: February 26, 2019
• Sponsor: University of Pennsylvania
• Collaborator: Hospira, now a wholly owned subsidiary of Pfizer
• Information provided by (Responsible Party): University of Pennsylvania

Tracking Information

• First Submitted Date: June 25, 2010
• First Posted Date: July 8, 2010
• Results First Submitted Date: August 29, 2018
• Results First Posted Date: October 31, 2018
• Last Update Posted Date: February 26, 2019
• Study Start Date: June 2010
• Actual Primary Completion Date: May 2012 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 3, 2018)

• Decreased Minute Ventilation [ Time Frame: During the bronchoscopy procedure only, 58.5 minutes average ]
  An initial baseline minute ventilation estimate was obtained via calibrated respiratory impedance plethysmography bands. Subsequent minute ventilation was normalized to this value. Values exceeding 100% were excluded from analysis, as these typically reflected a period of hyperpnea subsequent to relief of airway obstruction by chin lift or jaw thrust.
• Total Fentanyl [ Time Frame: During the bronchoscopy procedure only, 58.5 minutes average ]
  Total fentanyl dose delivered during the procedure
• Total Midazolam [ Time Frame: Duration of procedure ]
  Total midazolam delivered during procedure

Original Primary Outcome Measures (submitted: July 7, 2010)

• Minute ventilation [ Time Frame: About 2-3 hours during the bronchoscopy procedure only ]
  This will be assessed by calibrated respiratory inductance plethysmography
• Time to adequate sedation and procedure duration [ Time Frame: About 2-3 hours during the bronchoscopy procedure only ]
  Amount of time and duration of adequate sedation of the patient

Current Secondary Outcome Measures (submitted: October 3, 2018)

• Desaturation (Cumulative) [ Time Frame: During the bronchoscopy procedure only, 58.5 minutes average ]
  Cumulative time below saturation of 90% - the total number of seconds that the pulse oximeter reported a saturation below 90%
• Desaturation (Longest) [ Time Frame: During the bronchoscopy procedure only, 58.5 minutes average ]
  Longest time below saturation of 90% (the number of seconds elapsed between the start of a period in which the pulse oximeter saturation fell below 90% and the return above 90%)
• Conversion to General Anesthesia [ Time Frame: During the bronchoscopy procedure only, 58.5 minutes average ]
  Patients in which the procedure could not be completed without conversion to general anesthesia
• Patient Satisfaction [ Time Frame: After the bronchoscopy procedure only ]
  Satisfaction rated by 10 point Likert scale (0 = Totally dissatisfied, 10 = Totally satisfied)
• Endoscopist Satisfaction [ Time Frame: After the bronchoscopy procedure only ]
  Satisfaction rated by 10 point Likert scale (0 = Totally dissatisfied, 10 = Totally satisfied)

Original Secondary Outcome Measures (submitted: July 7, 2010)

• Cardiopulmonary stability [ Time Frame: About 2-3 hours during the bronchoscopy procedure only ]
  assessed by heart rate and pulse oximetry
• Patient compliance [ Time Frame: About 2-3 hours during the bronchoscopy procedure only ]
  assessed by the number of coughs per minute during the procedure
• Fentanyl/midazolam/benadryl consumption [ Time Frame: About 2-3 hours during the bronchoscopy procedure only ]
  The measurement of the amount of the standard of care sedation medications will be used during the procedure.
• Frequency of rescue from inadequate sedation [ Time Frame: About 2-3 hours during the bronchoscopy procedure only ]
  Measurement of time frame of inadequate sedation requiring intervention from the anesthesiologist.
• Patient and endoscopist satisfaction [ Time Frame: About 2-3 hours during the bronchoscopy procedure only ]
  assessed by Likert scale

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Alternative Sedation During Bronchoscopy
• Official Title: A Randomized, Placebo-controlled, Concealed Allocation Comparison of Respiratory Depression and Coughing During Bronchoscopy With Dexmedetomidine-ketamine as an Adjunct to Fentanyl-midazolam Sedation
• Brief Summary: This protocol hopes to determine whether the use of dexmedetomidine-ketamine can reduce the use of standard of care fentanyl-midazolam sedation during bronchoscopy. This may result in less respiratory depression while providing better compliance with the procedure.
• Detailed Description: All patients enrolled in the study will be undergoing bronchoscopy, which is typically performed with sedation. All procedural sedation carries some risk. Several features of the study may lower the risk of sedation relative to that of conventional sedation. An anesthesiologist will be present throughout the procedure. Continuous monitoring of respiration with RIP will be employed. Administration of sedation will be via a volumetric syringe pump. Benefits specific to dexmedetomidine-ketamine include the lack of respiratory depression and greater hemodynamic stability.
• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Treatment
• Condition: Sedation

Intervention

• Drug: Dexmedetomidine load
  Dexmedetomidine 1 µg/kg prior to bronchoscopy
  Other Names:

  • Precedex
  • Dexmedetomidine Hydrochloride
• Drug: Ketamine load
  Ketamine 30 mg bolus prior to bronchoscopy
  Other Names:

  • Ketalar
  • Calypsol
  • Ketamin
  • Ketaminol
  • Ketanest
  • Tekam
  • Vetalar
• Drug: Midazolam load
  2 mg bolus prior to bronchoscopy
  Other Name: Versed
• Drug: Fentanyl load
  50 µg bolus prior to bronchoscopy
  Other Names:

  • Abstral
  • Actiq
  • Fentora
  • Onsolis
• Drug: Dexmedetomidine maintenance
  0.5 µg/kg/hour for the duration of bronchoscopy (58.5 minutes average)
  Other Names:

  • Precedex
  • Dexmedetomidine Hydrochloride
• Drug: Ketamine maintenance
  8 µg/kg/min for the duration of bronchoscopy (58.5 minutes average)
  Other Names:

  • Ketalar
  • Calypsol
  • Ketamin
  • Ketaminol
  • Ketanest
  • Tekam
  • Vetalar
• Drug: Midazolam demand
  0.5 mg demand bolus at discretion of pulmonologist
  Other Name: Versed
• Drug: Fentanyl demand
  12.5 µg demand bolus at discretion of pulmonologist
  Other Names:

  • Abstral
  • Actiq
  • Fentora
  • Onsolis
• Drug: Benadryl demand
  25 mg bolus after 6th and 13th demand midazolam/fentanyl bolus
  Other Names:

  • Diphenhydramine Hcl
  • Aler-Dryl
  • Banophen
  • Ben Tann
  • Bromanate AF
  • Diphen
  • Diphenadryl
  • Diphenhist
  • Dytan
  • Unisom
  • Sominex
  • Silphen
  • Siladryl

Study Arms

• Placebo Comparator: Placebo
  midazolam load fentanyl load midazolam demand fentanyl demand benadryl demand
  Interventions:

  • Drug: Midazolam load
  • Drug: Fentanyl load
  • Drug: Midazolam demand
  • Drug: Fentanyl demand
  • Drug: Benadryl demand
• Active Comparator: dexmedetomidine and ketamine
  dexmedetomidine load ketamine load dexmedetomidine maintenance ketamine maintenance midazolam demand fentanyl demand benadryl demand
  Interventions:

  • Drug: Dexmedetomidine load
  • Drug: Ketamine load
  • Drug: Dexmedetomidine maintenance
  • Drug: Ketamine maintenance
  • Drug: Midazolam demand
  • Drug: Fentanyl demand
  • Drug: Benadryl demand

• Publications *: Yarmus LB, Akulian JA, Gilbert C, Mathai SC, Sathiyamoorthy S, Sahetya S, Harris K, Gillespie C, Haas A, Feller-Kopman D, Sterman D, Lee HJ. Comparison of moderate versus deep sedation for endobronchial ultrasound transbronchial needle aspiration. Ann Am Thorac Soc. 2013 Apr;10(2):121-6. doi: 10.1513/AnnalsATS.201209-074OC.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 7, 2010): 50
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: May 2012
• Actual Primary Completion Date: May 2012 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Adults over the age of 18 scheduled for elective flexible bronchoscopy in the endoscopy suite or OR of HUP

Exclusion Criteria:

• History of inability to complete bronchoscopy attributable to inadequate sedation
• Requiring more than 2 LPM supplemental oxygen to maintain SaO2 > 90%
• History of allergy to study medications
• Pregnancy
• A history of psychosis
• Any condition deemed likely by the pulmonologist or anesthesiologist to pose a significant risk due to elevation of blood pressure, including cerebral/aortic aneurysm, and or ischemic cardiovascular disease
• Bradydysrhythmia deemed significant by the anesthesiologist or pulmonologist
• A diagnosis of significant renal or hepatic impairment

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 90 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01158820
• Other Study ID Numbers: 810981
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: University of Pennsylvania
• Study Sponsor: University of Pennsylvania
• Collaborators: Hospira, now a wholly owned subsidiary of Pfizer

Investigators

• Principal Investigator: Jeff E Mandel, MD MS; University of Pennsylvania

• PRS Account: University of Pennsylvania
• Verification Date: February 2019