Sugammadex and Decreased Time to Extubation

NCT03196167 | Completed Phase 4 Results DMC FDA Drug

• 1 other identifier: 2000021124
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to demonstrate faster time to extubation after arrival in the cardiothoracic intensive care unit (ICU) in patients undergoing isolated coronary artery bypass grafting (CABG), AVR and AVR/CABG combination who receive Sugammadex as compared to placebo.

Conditions

Coronary Artery Bypass Graft and/or Aortic Valve Replacement Surgery

Keywords

sugammadex; extubation; CABG, AVR, CABG/AVR combination

Outcome Measures

Primary Outcomes (1)

• Time to Extubation

  The primary outcome of this study aims to test the time to extubation among patients in the cardiothoracic ICU who have undergone isolated CABG.

  Up to 2 weeks

Secondary Outcomes (7)

• Negative Inspiratory Force

  Up to 2 weeks

• RSBI

  Upto 2 weeks

• Length of ICU Stay

  Up to 2 weeks

• Length of Hospital Stay

  2 weeks

• New Dysrhythmia

  Up to 2 weeks

Study Arms (2)

Sugammadex

EXPERIMENTAL

Research pharmacy will provide the Sugammadex (2m/kg) vs. Placebo in a syringe.

Drug: Sugammadex

Placebo

PLACEBO COMPARATOR

Research pharmacy will provide the Sugammadex (2m/kg) vs. Placebo in a syringe.

Other: Placebo

Interventions

Sugammadex DRUG

The administration of the study and placebo compounds will be performed by CTICU nurses who will receive the drugs in a blinded fashion from the departmental research pharmacy.

Also known as: Bridion

Sugammadex

Placebo OTHER

The administration of the study and placebo compounds will be performed by CTICU nurses who will receive the drugs in a blinded fashion from the departmental research pharmacy.

Placebo

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All elective ARV, CABG cases, on-pump or off-pump, and CABG/AVR in adult patients with preoperative left ventricular ejection fraction (LVEF) ≥45%.

You may not qualify if:

• Emergency/unplanned cases.
• EF\<45% or moderate /severe RV dysfunction.
• Estimated GFR \< 30 mL/min.
• Patients on supplemental oxygen at baseline (home oxygen).
• BMI\>40 (calculated as the patient's weight in kilograms divided by the square of the patient's height in meters).
• Patients with chronic opioid use preoperatively.
• Patients with known neuromuscular disorders preoperatively.
• Patients with a known sensitivity to Rocuronium or to Sugammadex.
• Patients with known cognitive deficits preoperatively.
• Postoperative Bleeding (chest tube output \>100cc/hr ).
• Treatment of anaphylactoid reaction intraoperatively.
• Patient's temperature\<35.5 or \>38.3 degree Celsius at the time of ICU arrival.
• Determination that the patient will require prolonged mechanical ventilation possibly requiring muscle relaxation based on the intraoperative course and clinical judgment of the study PI or collaborating intensivists.
• Intraoperative hypoxia or on arrival to the ICU. (Please see Study Flowchart).
• Cardiac arrest.

Sponsors & Collaborators

• Yale University: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Yale University

New Haven, Connecticut, 06510, United States

Location

Related Publications (17)

• Hefner JL, Tripathi RS, Abel EE, Farneman M, Galloway J, Moffatt-Bruce SD. Quality Improvement Intervention to Decrease Prolonged Mechanical Ventilation After Coronary Artery Bypass Surgery. Am J Crit Care. 2016 Sep;25(5):423-30. doi: 10.4037/ajcc2016165.

  PMID: 27587423 BACKGROUND

• Cislaghi F, Condemi AM, Corona A. Predictors of prolonged mechanical ventilation in a cohort of 5123 cardiac surgical patients. Eur J Anaesthesiol. 2009 May;26(5):396-403. doi: 10.1097/EJA.0b013e3283232c69.

  PMID: 19276979 BACKGROUND

• Myles PS, Daly DJ, Djaiani G, Lee A, Cheng DC. A systematic review of the safety and effectiveness of fast-track cardiac anesthesia. Anesthesiology. 2003 Oct;99(4):982-7. doi: 10.1097/00000542-200310000-00035. No abstract available.

  PMID: 14508335 BACKGROUND

• Hawkes CA, Dhileepan S, Foxcroft D. Early extubation for adult cardiac surgical patients. Cochrane Database Syst Rev. 2003;(4):CD003587. doi: 10.1002/14651858.CD003587.

  PMID: 14583985 BACKGROUND

• van Mastrigt GA, Maessen JG, Heijmans J, Severens JL, Prins MH. Does fast-track treatment lead to a decrease of intensive care unit and hospital length of stay in coronary artery bypass patients? A meta-regression of randomized clinical trials. Crit Care Med. 2006 Jun;34(6):1624-34. doi: 10.1097/01.CCM.0000217963.87227.7B.

  PMID: 16614584 BACKGROUND

• Hillis LD, Smith PK, Anderson JL, Bittl JA, Bridges CR, Byrne JG, Cigarroa JE, Disesa VJ, Hiratzka LF, Hutter AM Jr, Jessen ME, Keeley EC, Lahey SJ, Lange RA, London MJ, Mack MJ, Patel MR, Puskas JD, Sabik JF, Selnes O, Shahian DM, Trost JC, Winniford MD. 2011 ACCF/AHA Guideline for Coronary Artery Bypass Graft Surgery: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2011 Dec 6;124(23):2610-42. doi: 10.1161/CIR.0b013e31823b5fee. Epub 2011 Nov 7. No abstract available.

  PMID: 22064600 BACKGROUND

• Hemmerling TM, Russo G, Bracco D. Neuromuscular blockade in cardiac surgery: an update for clinicians. Ann Card Anaesth. 2008 Jul-Dec;11(2):80-90. doi: 10.4103/0971-9784.41575.

  PMID: 18603747 BACKGROUND

• Abad-Gurumeta A, Ripolles-Melchor J, Casans-Frances R, Espinosa A, Martinez-Hurtado E, Fernandez-Perez C, Ramirez JM, Lopez-Timoneda F, Calvo-Vecino JM; Evidence Anaesthesia Review Group. A systematic review of sugammadex vs neostigmine for reversal of neuromuscular blockade. Anaesthesia. 2015 Dec;70(12):1441-52. doi: 10.1111/anae.13277.

  PMID: 26558858 BACKGROUND

• Murphy GS, Szokol JW, Marymont JH, Greenberg SB, Avram MJ, Vender JS. Residual neuromuscular blockade and critical respiratory events in the postanesthesia care unit. Anesth Analg. 2008 Jul;107(1):130-7. doi: 10.1213/ane.0b013e31816d1268.

  PMID: 18635478 BACKGROUND

• Fuchs-Buder T, Nemes R, Schmartz D. Residual neuromuscular blockade: management and impact on postoperative pulmonary outcome. Curr Opin Anaesthesiol. 2016 Dec;29(6):662-667. doi: 10.1097/ACO.0000000000000395.

  PMID: 27755128 BACKGROUND

• Murphy GS, Szokol JW, Vender JS, Marymont JH, Avram MJ. The use of neuromuscular blocking drugs in adult cardiac surgery: results of a national postal survey. Anesth Analg. 2002 Dec;95(6):1534-9, table of contents. doi: 10.1097/00000539-200212000-00012.

  PMID: 12456412 BACKGROUND

• Welliver M. New drug sugammadex: a selective relaxant binding agent. AANA J. 2006 Oct;74(5):357-63.

  PMID: 17048555 BACKGROUND

• Nicholson WT, Sprung J, Jankowski CJ. Sugammadex: a novel agent for the reversal of neuromuscular blockade. Pharmacotherapy. 2007 Aug;27(8):1181-8. doi: 10.1592/phco.27.8.1181.

  PMID: 17655516 BACKGROUND

• Chambers D, Paulden M, Paton F, Heirs M, Duffy S, Craig D, Hunter J, Wilson J, Sculpher M, Woolacott N. Sugammadex for the reversal of muscle relaxation in general anaesthesia: a systematic review and economic assessment. Health Technol Assess. 2010 Jul;14(39):1-211. doi: 10.3310/hta14390.

  PMID: 20688009 BACKGROUND

• Sorgenfrei IF, Norrild K, Larsen PB, Stensballe J, Ostergaard D, Prins ME, Viby-Mogensen J. Reversal of rocuronium-induced neuromuscular block by the selective relaxant binding agent sugammadex: a dose-finding and safety study. Anesthesiology. 2006 Apr;104(4):667-74. doi: 10.1097/00000542-200604000-00009.

  PMID: 16571960 BACKGROUND

• Sadleir PH, Russell T, Clarke RC, Maycock E, Platt PR. Intraoperative anaphylaxis to sugammadex and a protocol for intradermal skin testing. Anaesth Intensive Care. 2014 Jan;42(1):93-6. doi: 10.1177/0310057X1404200116.

  PMID: 24471669 BACKGROUND

• Rahe-Meyer N, Fennema H, Schulman S, Klimscha W, Przemeck M, Blobner M, Wulf H, Speek M, McCrary Sisk C, Williams-Herman D, Woo T, Szegedi A. Effect of reversal of neuromuscular blockade with sugammadex versus usual care on bleeding risk in a randomized study of surgical patients. Anesthesiology. 2014 Nov;121(5):969-77. doi: 10.1097/ALN.0000000000000424.

  PMID: 25208233 BACKGROUND

Related Links

• FDA information on Sugammadex

MeSH Terms

Interventions

Sugammadex

Intervention Hierarchy (Ancestors)

gamma-Cyclodextrins; Cyclodextrins; Macrocyclic Compounds; Polycyclic Compounds; Dextrins; Starch; Glucans; Polysaccharides; Carbohydrates

Limitations and Caveats

First this was a single center study. Second, we excluded patients undergoing mitral valve surgeries or those with moderate to severe LV dysfunction, as these patients often have preexisting pulmonary edema. Third, seven patients in the study were randomized but did not receive study drug or placebo.These were analyzed as intention to treat. Extubation time was defined from study drug administration to extubation. This definition was different from our a priori planned protocol.

Results Point of Contact

• Title: Amit Bardia
• Organization: Yale University

amit.bardia@yale.edu

2038436469

Study Officials

• Amit Bardia, MD

  Yale University

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The administration of the study and placebo compounds will be performed by CTICU nurses who will receive the drugs in a blinded fashion from the departmental research pharmacy.
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Patients will be enrolled using 1:1 randomization between active ingredient (intervention) and control arms, to be assigned randomly using a computer generated algorithm.

Study Record Dates

• First Submitted: June 20, 2017
• First Posted: June 22, 2017
• Study Start: May 13, 2017
• Primary Completion: October 1, 2020
• Study Completion: October 10, 2020
• Last Updated: January 14, 2022
• Results First Posted: January 14, 2022

Record last verified: 2022-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)