Propofol vs. Midazolam-based Balanced Propofol for Nonanesthesiologist Moderate Sedation in Colonoscopy

NCT01428882 | Completed Phase 4 Results DMC

• 1 other identifier: MIDP11
• Study Type: interventional
• Target: 135
• Locations: 1 country
• Sites: 1

Brief Summary

Nonanesthesiologist administration of propofol for sedation is actually a field of growing interest for endoscopists, as demonstrated by recent American and European guidelines on this issue. Propofol is a hypnotic drug with rapid onset and offset of action. Used as a single agent, it is commonly titrated to deep sedation, whereas balanced propofol sedation (BPS), which combines propofol with small doses of a benzodiazepine and/or an opioid, can be successfully titrated to moderate sedation. However, nonanesthesiologists propofol administration remains controversial on account of the possibility of deep sedation/general anesthesia related adverse events. On the other hand, the use of longer elimination half-life drugs, such as opioids and benzodiazepines, may theoretically prolong sedation and recovery. Up to date, no study has addressed a head-to-head comparison of both regimens administered by non-anesthesiologists and titrated to moderate sedation. This study aims to evaluate the impact on propofol sedation of premedication with a fixed dose of midazolam (2 mg)2 minutes before propofol administration targeted to moderate sedation, in terms of depth of sedation, recovery times, safety and satisfaction. The onset of sedative action of midazolam has been reported to be 1-2.5 minutes and the peak effect of midazolam occurs 8-12 minutes. Taking into account that colonoscopy usually lasts a minimum of 15-20 minutes, our hypothesis is that synergy between propofol and midazolam may increase the depth of sedation through the initial phases of the procedure, diminishing propofol requirements, but not prolonging significantly recovery times.

Conditions

Procedural Sedation

Keywords

Propofol; Midazolam; Moderate sedation; Deep sedation; Colonoscopy

Outcome Measures

Primary Outcomes (1)

• Level of Sedation Throughout the Entire Procedure

  Assessment every two minutes of the level of sedation during the endoscopic procedure, rating it as minimal, moderate or deep.

  Up to 1 hour after introduction of the colonoscope

Secondary Outcomes (3)

• Duration of Recovery After the Endoscopic Procedure

  Up to 1 hour after colonoscopy

• Rate of Sedation-related Complications During the Procedure and the Recovery Phases

  Up to two hours, including colonoscopy performance and recovery period

• Rate of Patients and Physician Satisfaction With Sedation

  Up to 1 hour after colonoscopy for endoscopists and up to 48 hours for patients

Study Arms (2)

Midazolam balanced propofol sedation

ACTIVE COMPARATOR

2 mg midazolam in 2 ml saline midazolam followed by continuous propofol iv infusion

Drug: Midazolam

Single-agent propofol sedation

PLACEBO COMPARATOR

2 ml saline followed by continuous propofol iv infusion

Drug: Propofol

Interventions

Midazolam DRUG

Midazolam (5 mg/5 mL) 2 mg before standard propofol induction (0.5-1.5 mg/Kg) and boluses-based sedation during colonoscopy, targeted to a moderate sedation level

Also known as: Not necessary

Midazolam balanced propofol sedation

Propofol DRUG

Placebo (normal saline 2 ml) before standard propofol induction (0.5-1.5 mg/Kg) and boluses-based sedation during colonoscopy, targeted to a moderate sedation level

Also known as: Not necessary

Single-agent propofol sedation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All patients undergoing elective outpatient colonoscopy

You may not qualify if:

• Age less than 18 years
• Allergy to propofol, soybeans, eggs or midazolam
• Chronic intake of benzodiazepines
• History of colorectal surgery
• ASA class IV, short and tick neck, difficult intubation due to inability to open the mouth widely
• Pregnancy
• Refusal, inability or unwillingness to give written consent
• Patients scheduled for advanced therapeutic colonoscopy or for more than one endoscopic procedure

Sponsors & Collaborators

• Infante, Javier Molina, M.D.: lead

Study Sites (1)

Hospital San Pedro de Alcantara

Cáceres, Caceres, 10003, Spain

Location

Related Publications (18)

• Cohen LB. Sedation issues in quality colonoscopy. Gastrointest Endosc Clin N Am. 2010 Oct;20(4):615-27. doi: 10.1016/j.giec.2010.07.003. Epub 2010 Aug 21.

  PMID: 20889067 BACKGROUND

• Singh H, Poluha W, Cheung M, Choptain N, Baron KI, Taback SP. Propofol for sedation during colonoscopy. Cochrane Database Syst Rev. 2008 Oct 8;2008(4):CD006268. doi: 10.1002/14651858.CD006268.pub2.

  PMID: 18843709 BACKGROUND

• Vargo JJ, Cohen LB, Rex DK, Kwo PY. Position statement: nonanesthesiologist administration of propofol for GI endoscopy. Gastrointest Endosc. 2009 Dec;70(6):1053-9. doi: 10.1016/j.gie.2009.07.020. No abstract available.

  PMID: 19962497 BACKGROUND

• Dumonceau JM, Riphaus A, Aparicio JR, Beilenhoff U, Knape JT, Ortmann M, Paspatis G, Ponsioen CY, Racz I, Schreiber F, Vilmann P, Wehrmann T, Wientjes C, Walder B; NAAP Task Force Members. European Society of Gastrointestinal Endoscopy, European Society of Gastroenterology and Endoscopy Nurses and Associates, and the European Society of Anaesthesiology Guideline: Non-anesthesiologist administration of propofol for GI endoscopy. Endoscopy. 2010 Nov;42(11):960-74. doi: 10.1055/s-0030-1255728. Epub 2010 Nov 11.

  PMID: 21072716 BACKGROUND

• Rex DK, Deenadayalu VP, Eid E, Imperiale TF, Walker JA, Sandhu K, Clarke AC, Hillman LC, Horiuchi A, Cohen LB, Heuss LT, Peter S, Beglinger C, Sinnott JA, Welton T, Rofail M, Subei I, Sleven R, Jordan P, Goff J, Gerstenberger PD, Munnings H, Tagle M, Sipe BW, Wehrmann T, Di Palma JA, Occhipinti KE, Barbi E, Riphaus A, Amann ST, Tohda G, McClellan T, Thueson C, Morse J, Meah N. Endoscopist-directed administration of propofol: a worldwide safety experience. Gastroenterology. 2009 Oct;137(4):1229-37; quiz 1518-9. doi: 10.1053/j.gastro.2009.06.042. Epub 2009 Jun 21.

  PMID: 19549528 BACKGROUND

• Cohen LB, Dubovsky AN, Aisenberg J, Miller KM. Propofol for endoscopic sedation: A protocol for safe and effective administration by the gastroenterologist. Gastrointest Endosc. 2003 Nov;58(5):725-32. doi: 10.1016/s0016-5107(03)02010-8.

  PMID: 14595310 BACKGROUND

• Cohen LB, Hightower CD, Wood DA, Miller KM, Aisenberg J. Moderate level sedation during endoscopy: a prospective study using low-dose propofol, meperidine/fentanyl, and midazolam. Gastrointest Endosc. 2004 Jun;59(7):795-803. doi: 10.1016/s0016-5107(04)00349-9.

  PMID: 15173791 BACKGROUND

• Rex DK, Deenadayalu V, Eid E. Gastroenterologist-directed propofol: an update. Gastrointest Endosc Clin N Am. 2008 Oct;18(4):717-25, ix. doi: 10.1016/j.giec.2008.06.002.

  PMID: 18922410 BACKGROUND

• McQuaid KR, Laine L. A systematic review and meta-analysis of randomized, controlled trials of moderate sedation for routine endoscopic procedures. Gastrointest Endosc. 2008 May;67(6):910-23. doi: 10.1016/j.gie.2007.12.046.

  PMID: 18440381 BACKGROUND

• Lee CK, Lee SH, Chung IK, Lee TH, Park SH, Kim EO, Lee SH, Kim HS, Kim SJ. Balanced propofol sedation for therapeutic GI endoscopic procedures: a prospective, randomized study. Gastrointest Endosc. 2011 Feb;73(2):206-14. doi: 10.1016/j.gie.2010.09.035. Epub 2010 Dec 18.

  PMID: 21168838 BACKGROUND

• Sipe BW, Scheidler M, Baluyut A, Wright B. A prospective safety study of a low-dose propofol sedation protocol for colonoscopy. Clin Gastroenterol Hepatol. 2007 May;5(5):563-6. doi: 10.1016/j.cgh.2007.01.013.

  PMID: 17478345 BACKGROUND

• VanNatta ME, Rex DK. Propofol alone titrated to deep sedation versus propofol in combination with opioids and/or benzodiazepines and titrated to moderate sedation for colonoscopy. Am J Gastroenterol. 2006 Oct;101(10):2209-17. doi: 10.1111/j.1572-0241.2006.00760.x.

  PMID: 17032185 BACKGROUND

• Rex DK. Review article: moderate sedation for endoscopy: sedation regimens for non-anaesthesiologists. Aliment Pharmacol Ther. 2006 Jul 15;24(2):163-71. doi: 10.1111/j.1365-2036.2006.02986.x.

  PMID: 16842446 BACKGROUND

• Paspatis GA, Manolaraki M, Xirouchakis G, Papanikolaou N, Chlouverakis G, Gritzali A. Synergistic sedation with midazolam and propofol versus midazolam and pethidine in colonoscopies: a prospective, randomized study. Am J Gastroenterol. 2002 Aug;97(8):1963-7. doi: 10.1111/j.1572-0241.2002.05908.x.

  PMID: 12190161 BACKGROUND

• Cohen LB. Making 1+1=3: improving sedation through drug synergy. Gastrointest Endosc. 2011 Feb;73(2):215-7. doi: 10.1016/j.gie.2010.10.027. No abstract available.

  PMID: 21295634 BACKGROUND

• Padmanabhan U, Leslie K, Eer AS, Maruff P, Silbert BS. Early cognitive impairment after sedation for colonoscopy: the effect of adding midazolam and/or fentanyl to propofol. Anesth Analg. 2009 Nov;109(5):1448-55. doi: 10.1213/ane.0b013e3181a6ad31. Epub 2009 Jul 17.

  PMID: 19617584 BACKGROUND

• Kerker A, Hardt C, Schlief HE, Dumoulin FL. Combined sedation with midazolam/propofol for gastrointestinal endoscopy in elderly patients. BMC Gastroenterol. 2010 Jan 27;10:11. doi: 10.1186/1471-230X-10-11.

  PMID: 20105314 BACKGROUND

• Molina-Infante J, Duenas-Sadornil C, Mateos-Rodriguez JM, Perez-Gallardo B, Vinagre-Rodriguez G, Hernandez-Alonso M, Fernandez-Bermejo M, Gonzalez-Huix F. Nonanesthesiologist-administered propofol versus midazolam and propofol, titrated to moderate sedation, for colonoscopy: a randomized controlled trial. Dig Dis Sci. 2012 Sep;57(9):2385-93. doi: 10.1007/s10620-012-2222-4. Epub 2012 May 22.

  PMID: 22615015 DERIVED

MeSH Terms

Interventions

Midazolam; Propofol

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Limitations and Caveats

Single center study. Small sample size. Fixed and relatively high-dose midazolam (2 mg). Lack of distinction between complications related to either pain stimuli or oversedation.

Results Point of Contact

• Title: Dr. Javier Molina-Infante
• Organization: Hospital San Pedro de Alcantara, Caceres

xavi_molina@hotmail.com

0034927621543

Study Officials

• Javier Molina-Infante, MD

  Hospital San Pedro de Alcantara, Caceres, Spain

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDIV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Doctor

Study Record Dates

• First Submitted: September 2, 2011
• First Posted: September 5, 2011
• Study Start: June 1, 2011
• Primary Completion: October 1, 2011
• Study Completion: December 1, 2011
• Last Updated: May 25, 2016
• Results First Posted: May 25, 2016

Record last verified: 2016-04

Data Sharing

• IPD Sharing: Will share

Locations

ES (1)