Comparison of Propofol/Alfentanil With Propofol/Ketamine (KET-001)

• ClinicalTrials.gov Identifier: NCT02000206
• Recruitment Status: Unknown
• First Posted: December 4, 2013
• Last Update Posted: December 4, 2013
• Sponsor: Rabin Medical Center
• Information provided by (Responsible Party): Mordechai Kremer, Rabin Medical Center

Tracking Information

• First Submitted Date: October 23, 2013
• First Posted Date: December 4, 2013
• Last Update Posted Date: December 4, 2013
• Study Start Date: February 2014
• Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 26, 2013)

• Percutaneous carbon dioxide tension [ Time Frame: Average expected time of 45 minutes ]
  Continuous measurements (record every 4 seconds). Throughout the duration of fiberoptic bronchoscopy - from the beginning of the procedure until 10 minutes after its termination.
• oxygen saturation [ Time Frame: Average expected time of 45 minutes. ]
  Continuous measurements (record every 4 seconds). Throughout the duration of fiberoptic bronchoscopy - from the beginning of the procedure until 10 minutes after its termination.
• heart rate [ Time Frame: Average expected time of 45 minutes ]
  Continuous measurements (record every 4 seconds). Throughout the duration of fiberoptic bronchoscopy - from the beginning of the procedure until 10 minutes after its termination.
• Non-invasive blood pressure [ Time Frame: Average expected time of 45 minutes ]
  Every 5 minutes. Throughout the duration of fiberoptic bronchoscopy - from the beginning of the procedure until 10 minutes after its termination

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted

Current Secondary Outcome Measures (submitted: November 26, 2013)

• Oxygen supplementation [ Time Frame: Average expected time of 45 minutes ]
  Significant hypoxemia, defined as functional SpO2 of 90%, will be treated initially with a jaw thrust maneuver. If it lasts more than few seconds, a naso/oropharyngeal tube will be inserted or supplemental oxygen will be delivered via face mask at 10 L min-1. The percentage of patients who needed supplemental oxygen will be evaluated
• Naso/oropharyngeal tube insertion [ Time Frame: Average expected time of 45 minutes ]
  Significant hypoxemia, defined as functional SpO2 of 90%, will be treated initially with jaw support. If it lasts more than few seconds, a naso/oropharyngeal tube will be inserted or supplemental oxygen will be delivered via face mask at 10 L min-1 The percentage of patients who needed Naso/oropharyngeal tube insertion will be evaluated
• A questionnaire evaluating pain and discomfort [ Time Frame: Ca. 30 minutes after the end of the procedure (average expected time of 60 minutes) ]
  A questionnaire evaluating pain and discomfort by Visual Analog Scale will be completed by the patient when awake after the procedure.(~30 minutes after the end of the procedure)
• A questionnaire evaluating the quality of sedation [ Time Frame: Immediately after end of procedure (average expected time of 30 minutes) ]
  A questionnaire evaluating the quality of sedation and the ease of performing the procedure by Visual Analog Scale will be completed by the bronchoscopist immediately after the procedure.
• Total propofol dosage [ Time Frame: Average expected time of 30 minutes ]
  The total amount of propofol used throughout the procedure will be calculated.
• Time to full awakening and orientation [ Time Frame: Anticipated to be in the range of 1-30 minutes after the end of the procedure ]
  Time from termination of the procedure to full awakening and orientation
• Time to discharge [ Time Frame: Average expected time of 60 minutes. Anticipated to be in the range of 45-120 minutes after the end of fiberoptic bronchoscopy ]
  The time from the termination of the procedure until the patient is discharged from the recovery unit will be measured.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Comparison of Propofol/Alfentanil With Propofol/Ketamine
• Official Title: Safety and Efficacy of Sedation for Flexible Fiberoptic Bronchoscopy: Comparison of Propofol/Alfentanil With Propofol/Ketamine
• Brief Summary: A prospective, randomized, patient-blinded comparison of the safety and efficacy of conscious sedation by propofol/alfentanil with propofol/ketamine in patients undergoing flexible fiberoptic bronchoscopy.

Detailed Description

The study group will include 80 patients undergoing flexible fiberoptic bronchoscopy(FFB).

Patients will be randomly assigned prior to the procedure to receive sedation by either propofol/alfentanil (PA group) or propofol/ketamine (PK group), using either the sealed envelope method or by computer randomization.

All patients will receive local anesthesia with Lidocaine 2% (total dose of 5-10 ml) that will be sprayed via the bronchoscope on the vocal cords before passage through them, as well as into the bronchial tree in order to suppress coughing.

In addition, patients from both groups will optionally receive intravenous Midazolam (up to a total dose of 0.05 mg/kg)if deemed necessary during the procedure.

Sedation will be started by 10-15 mcg/kg Alfentanil and 0.4 mg/kg Propofol, or by 0.2-0.3 mg/kg Ketamine and 0.4 mg/kg Propofol. It will be maintained by additional boluses of Propofol (aliquots of 10-50 mg) or by additional boluses of Propofol (aliquots of 10-50 mg) and/or Ketamine (aliquots of 5-25 mg).

All patients will receive supplemental oxygen via nasal cannula (2-4 L/min) before the beginning of the procedure.

Patients whose functional oxygen saturation (SpO2) prior to the beginning of the procedure will be lower than 92% while connected to a nasal cannula, will receive oxygen supplementation via a face mask.

If the SpO2 after initiation of sedation will fall below 90%, the patients' airways will be opened using a jaw-thrust maneuver or insertion of a nasal airway. Should the SpO2 remain low, the patient will receive oxygen supplementation via a face-mask.

If deemed necessary, additional safety measures will be taken by the anesthesiologist or by the performer of the bronchoscopy, such as administration of oxygen directly through the bronchoscope, assisted ventilation with an Ambu bag, and tracheal intubation.

The duration of bronchoscopy will be calculated from the administration of sedation until the flexible bronchoscope is removed from the tracheobronchial tree.

In all cases, patients will be monitored using continuous electrocardiography, pulse oximetry, and transcutaneous carbon dioxide (PtCO2, using a digital sensor placed on the patient's earlobe),and automated noninvasive blood pressure recordings every 5 minutes. All parameters will be recorded beginning from prior to connecting the patient to the nasal cannula before initiation of sedation, throughout the entire procedure and until 10 minutes after removal of the bronchoscope from the nasopharynx.

Immediately after the end of the procedure, the bronchoscopist will grade the quality of sedation (ease of performing the procedure) by Visual Analog Scale.

A questionnaire evaluating pain and discomfort by Visual Analog Scale will be completed by the patient when fully awake after the procedure.(~30 minutes after the end of the procedure).

Percutaneous carbon dioxide tension, blood oxygenation, heart rate, and blood pressure will be compared between the groups.

• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Single (Participant); Primary Purpose: Treatment
• Condition: Lung Disease

Intervention

• Drug: Propofol
  Other Name: Diprivan
• Drug: Ketamine
  Other Name: Ketalar
• Drug: Alfentanil
  Other Name: Alfenta

Study Arms

• Active Comparator: propofol + alfentanil

  Patients from the Propofol / Alfentanil group will receive in addition:

  1. A loading dose of 10-15 mcg/kg Alfentanil + 0.4 mg/kg Propofol, 2 minutes prior to the beginning of the procedure.
  2. Additional boluses of Propofol (aliquots of 10-50 mg) throughout the procedure if required
  Interventions:

  • Drug: Propofol
  • Drug: Alfentanil
• Active Comparator: propofol + ketamine

  Patients from the Propofol / Ketamine group will receive in addition:

  1. A loading dose of 0.2-0.3 mg/kg Ketamine + 0.4 mg/kg Propofol, 2 minutes prior to the beginning of the procedure.
  2. Additional boluses of Propofol (aliquots of 10-50 mg) and/or Ketamine (aliquots of 5-25 mg) throughout the procedure if required.
  Interventions:

  • Drug: Propofol
  • Drug: Ketamine

Publications *

• Stolz D, Chhajed PN, Leuppi JD, Brutsche M, Pflimlin E, Tamm M. Cough suppression during flexible bronchoscopy using combined sedation with midazolam and hydrocodone: a randomised, double blind, placebo controlled trial. Thorax. 2004 Sep;59(9):773-6.
• British Thoracic Society Bronchoscopy Guidelines Committee, a Subcommittee of Standards of Care Committee of British Thoracic Society. British Thoracic Society guidelines on diagnostic flexible bronchoscopy. Thorax. 2001 Mar;56 Suppl 1:i1-21.
• Gonzalez R, De-La-Rosa-Ramirez I, Maldonado-Hernandez A, Dominguez-Cherit G. Should patients undergoing a bronchoscopy be sedated? Acta Anaesthesiol Scand. 2003 Apr;47(4):411-5.
• Fox BD, Krylov Y, Leon P, Ben-Zvi I, Peled N, Shitrit D, Kramer MR. Benzodiazepine and opioid sedation attenuate the sympathetic response to fiberoptic bronchoscopy. Prophylactic labetalol gave no additional benefit. Results of a randomized double-blind placebo-controlled study. Respir Med. 2008 Jul;102(7):978-83. doi: 10.1016/j.rmed.2008.02.011. Epub 2008 Apr 3.
• Putinati S, Ballerin L, Corbetta L, Trevisani L, Potena A. Patient satisfaction with conscious sedation for bronchoscopy. Chest. 1999 May;115(5):1437-40.
• Stolz D, Kurer G, Meyer A, Chhajed PN, Pflimlin E, Strobel W, Tamm M. Propofol versus combined sedation in flexible bronchoscopy: a randomised non-inferiority trial. Eur Respir J. 2009 Nov;34(5):1024-30. doi: 10.1183/09031936.00180808. Epub 2009 Apr 22.
• Clark G, Licker M, Younossian AB, Soccal PM, Frey JG, Rochat T, Diaper J, Bridevaux PO, Tschopp JM. Titrated sedation with propofol or midazolam for flexible bronchoscopy: a randomised trial. Eur Respir J. 2009 Dec;34(6):1277-83. doi: 10.1183/09031936.00142108. Epub 2009 May 14.
• Crawford M, Pollock J, Anderson K, Glavin RJ, MacIntyre D, Vernon D. Comparison of midazolam with propofol for sedation in outpatient bronchoscopy. Br J Anaesth. 1993 Apr;70(4):419-22.
• White PF, Way WL, Trevor AJ. Ketamine--its pharmacology and therapeutic uses. Anesthesiology. 1982 Feb;56(2):119-36.
• Berkenbosch JW, Graff GR, Stark JM. Safety and efficacy of ketamine sedation for infant flexible fiberoptic bronchoscopy. Chest. 2004 Mar;125(3):1132-7.
• Slonim AD, Ognibene FP. Amnestic agents in pediatric bronchoscopy. Chest. 1999 Dec;116(6):1802-8.
• Hwang J, Jeon Y, Park HP, Lim YJ, Oh YS. Comparison of alfetanil and ketamine in combination with propofol for patient-controlled sedation during fiberoptic bronchoscopy. Acta Anaesthesiol Scand. 2005 Oct;49(9):1334-8.

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: November 26, 2013): 80
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 2014
• Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• American Society of Anesthesiologists grade I or II
• patients that will be referred to the procedure for bronchoalveolar lavage and cytologic/bacteriologic sampling, endoluminal biopsies for pathologic /bacteriologic analysis, or for regaining patency (mechanically or laser-assisted) of airways that are obstructed by secretions, tumors or foreign bodies

Exclusion Criteria:

• patient refusal or inability to provide informed consent
• American Society of Anesthesiologists grade III or higher
• allergy to study medications
• patients who have an endotracheal tube or tracheostomy

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Israel

Administrative Information

• NCT Number: NCT02000206
• Other Study ID Numbers: RMC13ctl
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Mordechai Kremer, Rabin Medical Center
• Study Sponsor: Rabin Medical Center
• Collaborators: Not Provided

Investigators

• Study Director: Mordechai R Kramer, MD; Rabin Medical Center

• PRS Account: Rabin Medical Center
• Verification Date: November 2013