Esmolol for Treatment of Perioperative Tachycardia

Phase 3

Terminated

• Conditions: High-risk, Non-cardiovascular Surgeries
• Interventions: Drug: Esmolol

• Registration Number: NCT01208402
• Lead Sponsor: Duke University

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 Timeline

• Study Start: 2010-09
• Study First Submitted: 2010-09-10
• Study First Submitted QC: 2010-09-22
• Study First Posted: 2010-09-24
• Primary Completion: 2013-07
• Study Completion: 2013-07
• Status Verified: 2014-11
• Results First Submitted: 2014-11-13
• Results First Submitted QC: 2014-11-13
• Results First Posted: 2014-11-19
• Last Update Submitted: 2014-11-25
• Last Update Posted: 2014-12-12

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 76

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
oral long acting beta blocker	Esmolol	oral administration of long acting beta blocker as standard of care on the day of surgery
Esmolol infusion	Esmolol	given 30 minutes prior to induction up to 12 hours post-op

Primary Outcome Measures

Name	Time	Method
Percentage of Postoperative Hours 4 to 12 With Heart Rate (HR) <60 or >80 Bpm.	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.
Percentage of Intraoperative Case Time With Heart Rate (HR) <60 or >80 Bpm	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	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.

Secondary Outcome Measures

Name	Time	Method
Percentage of Postoperative First Three Hours With Systolic Blood Pressure <95 mmHg	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 Intraoperative Case Time With Systolic Blood Pressure <95 mmHg	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 Hours 4 to 12 With Systolic Blood Pressure <95 mmHg	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.

Trial Locations

Locations (3)

Durham VA Medical Center; 🇺🇸 Durham, North Carolina, United States

Ohio State University; 🇺🇸 Columbus, Ohio, United States

Duke University Medical Center; 🇺🇸 Durham, North Carolina, United States