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Esmolol for Treatment of Perioperative Tachycardia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01208402
Recruitment Status : Terminated (Baxter has terminated the study for inadequate enrollment rate accrual.)
First Posted : September 24, 2010
Results First Posted : November 19, 2014
Last Update Posted : December 12, 2014
Sponsor:
Collaborator:
Baxter Healthcare Corporation
Information provided by (Responsible Party):
Duke University

Tracking Information
First Submitted Date  ICMJE September 10, 2010
First Posted Date  ICMJE September 24, 2010
Results First Submitted Date  ICMJE November 13, 2014
Results First Posted Date  ICMJE November 19, 2014
Last Update Posted Date December 12, 2014
Study Start Date  ICMJE September 2010
Actual Primary Completion Date July 2013   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 25, 2014)
  • Percentage of Intraoperative Case Time With Heart Rate (HR) <60 or >80 Bpm [ Time Frame: Start of surgery to end of surgery, an average duration of 245 minutes ]
    Duration of intraoperative excursion (ie, time spent) outside Target HR range defined as 60 to 80 bpm during surgery, expressed as percent of case minutes. Vital signs are measured from start of surgery to end of surgery at 5 minute intervals or less.
  • Percentage of Postoperative First Three Hours With Heart Rate (HR) <60 or >80 Bpm [ Time Frame: End of surgery to 3 hours ]
    Duration of postoperative first three hours spent outside Target HR range defined as 60 to 80 bpm, expressed as percent of the total 3 hours. Vital signs are measured from end of surgery to 3 hours postoperatively at 5 minute intervals for the first hour and every 15 minutes thereafter.
  • Percentage of Postoperative Hours 4 to 12 With Heart Rate (HR) <60 or >80 Bpm. [ Time Frame: Postoperative hours 4-12 ]
    Duration of postoperative hours 4 to 12 spent outside Target HR range defined as 60 to 80 bpm, expressed as percent of the total 9 hours. Vital signs are measured during hours four and five at 30 minute intervals and once every hour for the next 7 hours, through 12 hours postoperatively.
Original Primary Outcome Measures  ICMJE
 (submitted: September 22, 2010)
Efficacy of continuous perioperative infusion of esmolol [ Time Frame: 30 minutes prior to induction until 12 hours after surgery ]
Incidence of perioperative excursion (ie, time spent) outside Target HR range defined as 60 to 80 bpm during continuos infusion of esmolol from immediate pre-operative period up to 12 hours post-operatively
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 25, 2014)
  • Percentage of Intraoperative Case Time With Systolic Blood Pressure <95 mmHg [ Time Frame: Start of surgery to end of surgery, an average duration of 245 minutes ]
    Duration of intraoperative case time patient was not in the target window of SBP > 95 mmHg, expressed as percent of total case minutes. SBP is measured from start of surgery to end of surgery at 5 minute intervals or less.
  • Percentage of Postoperative First Three Hours With Systolic Blood Pressure <95 mmHg [ Time Frame: end of surgery to 3 hours ]
    Duration of postoperative first three hours patient was not in the target window of SBP > 95 mmHg, expressed as percent of the total 3 hours. SBP is measured from end of surgery to 3 hours postoperatively at 5 minute intervals for first hour and every 15 minutes thereafter.
  • Percentage of Postoperative Hours 4 to 12 With Systolic Blood Pressure <95 mmHg [ Time Frame: Postoperative hours 4-12 ]
    Duration of postoperative hours 4 to 12 patient was not in the target window of SBP > 95 mmHg, expressed as percent of the total 9 hours. SBP was measured during hours four and five at 30 minute intervals and once every hour for the next 7 hours, through 12 hours postoperatively.
Original Secondary Outcome Measures  ICMJE
 (submitted: September 22, 2010)
Safety of continuous perioperative infusion of esmolol [ Time Frame: 30 minutes prior to induction until 12 hours after surgery ]
Perioperative incidence of hypotension. In addition we will determine and assess incidence of ischemic adverse events (myocardial, cerebral, renal), the need for rescue therapy (therapy other than study drug) to maintain HR & BP target), the discontinuation rate of study drug, total infusion time to maintain a min SBP of 95 mmHg , total period of time patients are not in the target window of SBP > 95 mmHg, total period of time patients have bradycardia and a subgroup analysis to evaluate other non invasive hemodynamic parameters (e.g. CO, SV, SVV).
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Esmolol for Treatment of Perioperative Tachycardia
Official Title  ICMJE Safety and Efficacy of Esmolol for the Treatment of Peri-operative Tachycardia in Patients at Risk for Post Operative Adverse Ischemic Outcomes
Brief Summary The purpose of this study is to find out if Esmolol is a safe and effective alternative treatment compared to standard treatment using a long acting beta blocker drug, in controlling abnormal heart rate before, during and immediately after surgery.
Detailed Description

The benefit versus risk of perioperative beta blockade therapy for adverse ischemic event risk reduction in high risk patients undergoing non-cardiac surgery has been recently challenged. In particular the PeriOperative Ischemia Study Evaluation (POISE trial) showed a cardio-protective effect only at the expense of a higher incidence of stroke and all-cause mortality . In that study death and stroke were significantly associated with an increase in hypotension and bradycardia. Long acting agents - aggressively administered to achieve heart rate (HR) control - appear to be associated with significant adverse outcomes (death, stroke) despite myocardial ischemia and infarction reduction.

It is estimated that 20 percent of high risk patients come to surgery with chronic beta blocker oral therapy. The American Heart Association recommends continuation of beta blockers in this situation as beta-blocker withdrawal is associated with increased rate of perioperative myocardial infarction . Protocols optimizing the perioperative administration of beta-blockers in high-risk patients are therefore needed.

Esmolol is a cardioselective beta-blocker with a short elimination half-life (t1/2 = 9.2 min) and no intrinsic sympathomimetic activity. Evidence has revealed that Esmolol, with its unique short half life can be quickly titrated to both achieve a target hemodynamic effect as well as reduce (or loose) its effect quickly in unstable situations thereby mitigates undesired hypotension and / or bradycardia.

This study proposes to assess the Safety and Efficacy of dosing to target endpoints with Esmolol - an ultra short acting beta blocker - the day of surgery compared to standard long acting oral Metoprolol the day of surgery.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
Condition  ICMJE High-risk, Non-cardiovascular Surgeries
Intervention  ICMJE Drug: Esmolol
Infusion will be started at 50 mcg/kg/min for 4 minutes and titrated in increments of 50 mcg/kg/min up to a maximum of 300mcg/kg/min (maintenance dose) to maintain a heart rate between 60 and 80 beats per minute (bpm) while maintaining a minimum systolic blood pressure (SBP) of 95 mmHg during the length of surgery and up to 12 hours post-operatively.
Other Name: Brevibloc
Study Arms  ICMJE
  • Active Comparator: oral long acting beta blocker
    oral administration of long acting beta blocker as standard of care on the day of surgery
    Intervention: Drug: Esmolol
  • Experimental: Esmolol infusion
    given 30 minutes prior to induction up to 12 hours post-op
    Intervention: Drug: Esmolol
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: November 13, 2014)
76
Original Estimated Enrollment  ICMJE
 (submitted: September 22, 2010)
220
Actual Study Completion Date  ICMJE July 2013
Actual Primary Completion Date July 2013   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Males or Females
  2. Age > 40y/o
  3. Scheduled high risk (ASA II-IV) non-cardiac surgery with anticipated 12 hour post-operative ICU care
  4. Written informed consent
  5. Patients on a stable chronic oral beta-blocker therapy
  6. Revised Cardiac Risk Index 1(below) Cardiac Risk Index 1 or greater (below)

    • a history of coronary disease
    • a history of congestive heart failure
    • a history of treated diabetes
    • a history of cerebrovascular disease
    • a history of chronic renal failure

Exclusion Criteria:

  1. Active bleeding
  2. Untreated left main disease
  3. Active cardiac condition (eg unstable angina pectoris, acute exacerbation of CHF, serious arrhythmias, symptomatic valve disease)
  4. Preoperative positive troponin T
  5. Contraindication for esmolol use
  6. Previous allergy or intolerance to esmolol
  7. Cancer with an expected life expectancy < 6 months
  8. Pregnancy or lactating or planning to become pregnant
  9. Failure to provide informed consent, unable to understand or follow instructions.
  10. History of drug allergy or idiosyncrasy to beta-adrenergic drugs
  11. Recent history (within 1 year) of drug or alcohol abuse
  12. Patients with a Pacemaker
  13. Abnormal liver function Child-Pugh - B
  14. Body Mass Index > 45
  15. Reactive airway disease (defined as a history of hospitalization with status asthmaticus within the past one year)
  16. Surgery scheduled to begin after 2pm
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 41 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01208402
Other Study ID Numbers  ICMJE Pro00024224
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Duke University
Original Responsible Party Solomon Aronson - Professor Department of Anesthesiology, Duke University Medical Center
Current Study Sponsor  ICMJE Duke University
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Baxter Healthcare Corporation
Investigators  ICMJE
Principal Investigator: Solomon Aronson, MD Duke University
PRS Account Duke University
Verification Date November 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP