Study to Determine if the Midazolam-Meperidine-Dexmedetomidine is Superior to the Midazolam-Meperidine for Sedation During ERCP

NCT01404689 | Completed Phase 4 DMC

• 1 other identifier: SNUBH-129-012
• Study Type: interventional
• Target: 110
• Locations: 1 country
• Sites: 1

Brief Summary

Endoscopic retrograde cholangiopancreatography (ERCP) takes a longer time and is more complex to perform than the other parallel procedures, causing discomfort to patients. It is commonly performed under sedation endoscopy. Until recently, the combination administration of midazolam and opioid has been widely used as standard therapy due to its superior sedation effect compared to the other sedation agents. Midazolam, however, has problems, such as an insufficient sedation effect and an intermittent paradoxical response. Unlike midazolam, propofol has no antagonist and may cause problems such as respiratory depression, and has a narrow therapeutic range for the sedation effect, consequently requiring supervision by experienced experts, although it has a better sedation effect than midazolam. Due to these disadvantages, propofol is clinically less useful than midazolam. Meanwhile, dexmedetomidine, a selective α2 adrenergic agonist, is known to maintain the proper level of sedation and has a weak influence on respiratory depression. Recent studies have shown positive results with dexmedetomidine in relation with the sedation effect for surgery patients under local anesthesia or in intensive care units. As such, extensive studies are being conducted on the use of dexmedetomidine in endoscopic procedures due to the increased attention to dexmedetomidine. This notwithstanding, the clinical usefulness of dexmedetomidine is still debatable. In particular, studies on the use of dexmedetomidine for ERCP are very rare. Given the recent idea that dexmedetomidine may exert a synergistic effect in combination with midazolam, these authors endeavored to prospectively compare and analyze the sedation effect and adverse events, including respiratory depression, of the combination therapy of midazolam and meperidine, both of which have been widely used in patients undergoing ERCP, and of the combination therapy of midazolam, meperidine, and dexmedetomidine. The small-scale comparative study on the combination administration of propofol and fentanyl, which has a high risk of causing complications, and on the single administration of dexmedetomidine is the only study on the sedation effect of dexmedetomidine in the ERCP procedure that has yet been conducted; there has been no study that investigated the effect of the combination administration of dexmedetomidine and other drugs in the ERCP procedure. This study is thus expected to contribute to the development of guidelines on sedation in the ERCP procedure.

Conditions

Undergoing ERCP for Diagnostic or Therapeutic Purposes

Keywords

dexmedetomidine; midazolam; ERCP; cholangiopancreatography; sedation; propofol

Outcome Measures

Primary Outcomes (1)

• Level of sedation

  The sedation level recorded by the RSS and the requirement of the additional sedative (midazolam) or the analgesic (meperidine), and the proportion (%) of cases where adequate sedation was maintained during entire procedure time.

  During entire procedure(ERCP) time; an expected average of the procedure time is 20 minutes

Secondary Outcomes (1)

• Complication rate

  From start point of the procedure(ERCP) to 60 minutes after the procedure

Study Arms (2)

Midazolam-Meperidine-Dexmedetomidine

EXPERIMENTAL

midazolam 0.06mg/kg IV bolus, meperidine 50mg IV bolus and dexmedetomidine 1μg/Kg•hr infusion (30% reduction of midazolam dose and 25mg of meperidine for patients 65 years of age or older)

Drug: Dexmedetomidine

Midazolam-Meperidine

SHAM COMPARATOR

midazolam 0.06mg/kg IV bolus, meperidine 50mg IV bolus and placebo(saline) infusion(30% reduction of midazolam dose and 25mg of meperidine for patients 65 years of age or older)

Other: normal saline

Interventions

Dexmedetomidine DRUG

dexmedetomidine 1μg/Kg•hr IV continuous infusion, initiated 15 min before the procedure (ERCP) till complete procedure

Also known as: Precedex® 100μg/1ml vial: DMDTIA

Midazolam-Meperidine-Dexmedetomidine

normal saline OTHER

0.9% NaCl 1μg/Kg•hr IV continuous infusion, initiated 15 min before the procedure (ERCP) till complete procedure

Also known as: NaCl 0.9% 20ml plastic ample: NSIP

Midazolam-Meperidine

Eligibility Criteria

• Age: 20 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Those who are admitted for diagnostic and therapeutic ERCPs
• aged 20 to 80 years
• American Society of Anesthesiologists (ASA) classification I to III

You may not qualify if:

• ASA physical status IV and V
• allergic to any components of sedation and opioid drugs
• patients with chronic illicit drug use

Sponsors & Collaborators

• Seoul National University Hospital: lead
• Hana Pharm Co., Ltd.: collaborator

Study Sites (1)

Division of Gastroenterology, Department of Internal Medicine, Seoul National University Bundang Hospital

Seongnam-si, Gyeonggi-do, 463-707, South Korea

Location

Related Publications (19)

• Standards of Practice Committee of the American Society for Gastrointestinal Endoscopy; Lichtenstein DR, Jagannath S, Baron TH, Anderson MA, Banerjee S, Dominitz JA, Fanelli RD, Gan SI, Harrison ME, Ikenberry SO, Shen B, Stewart L, Khan K, Vargo JJ. Sedation and anesthesia in GI endoscopy. Gastrointest Endosc. 2008 Nov;68(5):815-26. doi: 10.1016/j.gie.2008.09.029. No abstract available.

  PMID: 18984096 BACKGROUND

• Yuksel O, Parlak E, Koklu S, Ertugrul I, Tunc B, Sahin B. Conscious sedation during endoscopic retrograde cholangiopancreatography: midazolam or midazolam plus meperidine? Eur J Gastroenterol Hepatol. 2007 Nov;19(11):1002-6. doi: 10.1097/MEG.0b013e3282cf5167.

  PMID: 18049171 BACKGROUND

• Reimann FM, Samson U, Derad I, Fuchs M, Schiefer B, Stange EF. Synergistic sedation with low-dose midazolam and propofol for colonoscopies. Endoscopy. 2000 Mar;32(3):239-44. doi: 10.1055/s-2000-134.

  PMID: 10718390 BACKGROUND

• Honan VJ. Paradoxical reaction to midazolam and control with flumazenil. Gastrointest Endosc. 1994 Jan-Feb;40(1):86-8. doi: 10.1016/s0016-5107(94)70020-6. No abstract available.

  PMID: 8163147 BACKGROUND

• Chen WX, Lin HJ, Zhang WF, Gu Q, Zhong XQ, Yu CH, Li YM, Gu ZY. Sedation and safety of propofol for therapeutic endoscopic retrograde cholangiopancreatography. Hepatobiliary Pancreat Dis Int. 2005 Aug;4(3):437-40.

  PMID: 16109532 BACKGROUND

• Kongkam P, Rerknimitr R, Punyathavorn S, Sitthi-Amorn C, Ponauthai Y, Prempracha N, Kullavanijaya P. Propofol infusion versus intermittent meperidine and midazolam injection for conscious sedation in ERCP. J Gastrointestin Liver Dis. 2008 Sep;17(3):291-7.

  PMID: 18836622 BACKGROUND

• Ladas SD, Aabakken L, Rey JF, Nowak A, Zakaria S, Adamonis K, Amrani N, Bergman JJ, Boix Valverde J, Boyacioglu S, Cremers I, Crowe J, Deprez P, Dite P, Eisen M, Eliakim R, Fedorov ED, Galkova Z, Gyokeres T, Heuss LT, Husic-Selimovic A, Khediri F, Kuznetsov K, Marek T, Munoz-Navas M, Napoleon B, Niemela S, Pascu O, Perisic N, Pulanic R, Ricci E, Schreiber F, Svendsen LB, Sweidan W, Sylvan A, Teague R, Tryfonos M, Urbain D, Weber J, Zavoral M; European Society of Gastrointestinal Endoscopy Survey of National Endoscopy Society Members. Use of sedation for routine diagnostic upper gastrointestinal endoscopy: a European Society of Gastrointestinal Endoscopy Survey of National Endoscopy Society Members. Digestion. 2006;74(2):69-77. doi: 10.1159/000097466. Epub 2006 Nov 27.

  PMID: 17135728 BACKGROUND

• Cohen LB, Delegge MH, Aisenberg J, Brill JV, Inadomi JM, Kochman ML, Piorkowski JD Jr; AGA Institute. AGA Institute review of endoscopic sedation. Gastroenterology. 2007 Aug;133(2):675-701. doi: 10.1053/j.gastro.2007.06.002. No abstract available.

  PMID: 17681185 BACKGROUND

• Kamibayashi T, Maze M. Clinical uses of alpha2 -adrenergic agonists. Anesthesiology. 2000 Nov;93(5):1345-9. doi: 10.1097/00000542-200011000-00030. No abstract available.

  PMID: 11046225 BACKGROUND

• Kunisawa T, Hanada S, Kurosawa A, Suzuki A, Takahata O, Iwasaki H. Dexmedetomidine was safely used for sedation during spinal anesthesia in a very elderly patient. J Anesth. 2010 Dec;24(6):938-41. doi: 10.1007/s00540-010-1025-z. Epub 2010 Oct 7.

  PMID: 21110048 BACKGROUND

• Dere K, Sucullu I, Budak ET, Yeyen S, Filiz AI, Ozkan S, Dagli G. A comparison of dexmedetomidine versus midazolam for sedation, pain and hemodynamic control, during colonoscopy under conscious sedation. Eur J Anaesthesiol. 2010 Jul;27(7):648-52. doi: 10.1097/EJA.0b013e3283347bfe.

  PMID: 20531094 BACKGROUND

• Boehm CA, Carney EL, Tallarida RJ, Wilson RP. Midazolam enhances the analgesic properties of dexmedetomidine in the rat. Vet Anaesth Analg. 2010 Nov;37(6):550-6. doi: 10.1111/j.1467-2995.2010.00565.x.

  PMID: 21040379 BACKGROUND

• Bol CJ, Vogelaar JP, Tang JP, Mandema JW. Quantification of pharmacodynamic interactions between dexmedetomidine and midazolam in the rat. J Pharmacol Exp Ther. 2000 Jul;294(1):347-55.

  PMID: 10871332 BACKGROUND

• Salonen M, Onaivi ES, Maze M. Dexmedetomidine synergism with midazolam in the elevated plus-maze test in rats. Psychopharmacology (Berl). 1992;108(1-2):229-34. doi: 10.1007/BF02245313.

  PMID: 1357706 BACKGROUND

• Bergese SD, Patrick Bender S, McSweeney TD, Fernandez S, Dzwonczyk R, Sage K. A comparative study of dexmedetomidine with midazolam and midazolam alone for sedation during elective awake fiberoptic intubation. J Clin Anesth. 2010 Feb;22(1):35-40. doi: 10.1016/j.jclinane.2009.02.016.

  PMID: 20206849 BACKGROUND

• Dasta JF, Jacobi J, Sesti AM, McLaughlin TP. Addition of dexmedetomidine to standard sedation regimens after cardiac surgery: an outcomes analysis. Pharmacotherapy. 2006 Jun;26(6):798-805. doi: 10.1592/phco.26.6.798.

  PMID: 16716133 BACKGROUND

• Heard C, Burrows F, Johnson K, Joshi P, Houck J, Lerman J. A comparison of dexmedetomidine-midazolam with propofol for maintenance of anesthesia in children undergoing magnetic resonance imaging. Anesth Analg. 2008 Dec;107(6):1832-9. doi: 10.1213/ane.0b013e31818874ee.

  PMID: 19020127 BACKGROUND

• Muller S, Borowics SM, Fortis EA, Stefani LC, Soares G, Maguilnik I, Breyer HP, Hidalgo MP, Caumo W. Clinical efficacy of dexmedetomidine alone is less than propofol for conscious sedation during ERCP. Gastrointest Endosc. 2008 Apr;67(4):651-9. doi: 10.1016/j.gie.2007.09.041. Epub 2008 Mar 4.

  PMID: 18291396 BACKGROUND

• Lee BS, Ryu J, Lee SH, Lee MG, Jang SE, Hwang JH, Ryu JK, Do SH, Kim YT. Midazolam with meperidine and dexmedetomidine vs. midazolam with meperidine for sedation during ERCP: prospective, randomized, double-blinded trial. Endoscopy. 2014 Apr;46(4):291-8. doi: 10.1055/s-0033-1358909. Epub 2014 Mar 26.

  PMID: 24671858 DERIVED

Related Links

• Web site of Seoul National University Bundang Hospital
• Web site of Seoul National University College of Medicine
• Web site of Korea Food and Drug Administration

MeSH Terms

Interventions

Dexmedetomidine; Saline Solution

Intervention Hierarchy (Ancestors)

Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Sang Hyub Lee, M.D. Ph.D

  Assistant Professor of Internal Medicine, Seoul National University College of Medicine and Seoul National University Bundang Hospital

  STUDY DIRECTOR

• Ban Seok Lee, M.D.

  Fellowship doctor, Division of Gastroenterology, Department of Internal Medicine, Seoul National University Bundang Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Internal Medicine, Seoul National University College of Medicine and Seoul National University Bundang Hospital

Study Record Dates

• First Submitted: July 24, 2011
• First Posted: July 28, 2011
• Study Start: August 1, 2011
• Primary Completion: March 1, 2012
• Study Completion: March 1, 2012
• Last Updated: July 16, 2013

Record last verified: 2013-07

Locations

KR (1)