Esmolol for Treatment of Perioperative Tachycardia

High-risk, Non-cardiovascular Surgeries Clinical Trial

Official title:

Safety and Efficacy of Esmolol for the Treatment of Peri-operative Tachycardia in Patients at Risk for Post Operative Adverse Ischemic Outcomes

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01208402
• Other study ID #: Pro00024224
• Status: Terminated
• Phase: Phase 3
• First received: September 10, 2010
• Last updated: November 25, 2014
• Start date: September 2010
• Est. completion date: July 2013

Study information

• Verified date: November 2014
• Source: Duke University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 76
• Est. completion date: July 2013
• Est. primary completion date: July 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 41 Years and older

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Subject), Primary Purpose: Treatment

Related Conditions & MeSH terms

• High-risk, Non-cardiovascular Surgeries
• Tachycardia

Intervention

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.

Locations

Country	Name	City	State
United States	Ohio State University	Columbus	Ohio
United States	Duke University Medical Center	Durham	North Carolina
United States	Durham VA Medical Center	Durham	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Duke University	Baxter Healthcare Corporation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Intraoperative Case Time With Heart Rate (HR) <60 or >80 Bpm	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.	Start of surgery to end of surgery, an average duration of 245 minutes	Yes
Primary	Percentage of Postoperative First Three Hours With Heart Rate (HR) <60 or >80 Bpm	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.	End of surgery to 3 hours	Yes
Primary	Percentage of Postoperative Hours 4 to 12 With Heart Rate (HR) <60 or >80 Bpm.	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.	Postoperative hours 4-12	Yes
Secondary	Percentage of Intraoperative Case Time With Systolic Blood Pressure <95 mmHg	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.	Start of surgery to end of surgery, an average duration of 245 minutes	Yes
Secondary	Percentage of Postoperative First Three Hours With Systolic Blood Pressure <95 mmHg	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.	end of surgery to 3 hours	Yes
Secondary	Percentage of Postoperative Hours 4 to 12 With Systolic Blood Pressure <95 mmHg	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.	Postoperative hours 4-12	Yes