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Esmolol for Treatment of Perioperative Tachycardia

This study has been terminated.
(Baxter has terminated the study for inadequate enrollment rate accrual.)
Sponsor:
Collaborator:
Baxter Healthcare Corporation
Information provided by (Responsible Party):
Duke University
ClinicalTrials.gov Identifier:
NCT01208402
First received: September 10, 2010
Last updated: November 13, 2014
Last verified: November 2014
  Purpose

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.


Condition Intervention Phase
High-risk, Non-cardiovascular Surgeries
Drug: Esmolol
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
Official Title: Safety and Efficacy of Esmolol for the Treatment of Peri-operative Tachycardia in Patients at Risk for Post Operative Adverse Ischemic Outcomes

Resource links provided by NLM:


Further study details as provided by Duke University:

Primary Outcome Measures:
  • Percentage of Intraoperative Case Time With Heart Rate (HR) <60 or >80 Bpm [ Time Frame: Start of surgery to end of surgery ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Percentage of Intraoperative Case Time With Systolic Blood Pressure <95 mmHg [ Time Frame: Start of surgery to end of surgery ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 76
Study Start Date: September 2010
Study Completion Date: July 2013
Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: oral long acting beta blocker
oral administration of long acting beta blocker as standard of care on the day of surgery
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
Experimental: Esmolol infusion
given 30 minutes prior to induction up to 12 hours post-op
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

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.

  Eligibility

Ages Eligible for Study:   41 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01208402

Locations
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
Durham VA Medical Center
Durham, North Carolina, United States, 27705
United States, Ohio
Ohio State University
Columbus, Ohio, United States, 43210
Sponsors and Collaborators
Duke University
Baxter Healthcare Corporation
Investigators
Principal Investigator: Solomon Aronson, MD Duke University
  More Information

No publications provided

Responsible Party: Duke University
ClinicalTrials.gov Identifier: NCT01208402     History of Changes
Other Study ID Numbers: Pro00024224
Study First Received: September 10, 2010
Results First Received: November 13, 2014
Last Updated: November 13, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Tachycardia
Arrhythmias, Cardiac
Cardiovascular Diseases
Heart Diseases
Pathologic Processes
Esmolol
Adrenergic Agents
Adrenergic Antagonists
Adrenergic beta-1 Receptor Antagonists
Adrenergic beta-Antagonists
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on November 20, 2014