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Tight Hemodynamic Control in Patients Who Are Chronically on Metoprolol

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. Identifier: NCT01404767
Recruitment Status : Terminated (Enrollment slow over 2 years a change in the population less on metoprolol than initially anticipated)
First Posted : July 28, 2011
Last Update Posted : April 21, 2015
Baxter Healthcare Corporation
Information provided by (Responsible Party):
University Health Network, Toronto

Tracking Information
First Submitted Date  ICMJE June 21, 2011
First Posted Date  ICMJE July 28, 2011
Last Update Posted Date April 21, 2015
Study Start Date  ICMJE April 2011
Actual Primary Completion Date April 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 27, 2011)
The difference between plasma levels of metoprolol within two groups [ Time Frame: 0,1, 2, 4, 8, 12, 24 hours post intervention ]
Comparisons measured in the pre-operative to intra-operative and post operative periods within metoprolol arm as well as between esmolol arm and metoprolol arm. Plasma levels will be correlated with both the hemodynamic response (HR) and the incidence of postoperative ischemia. The covariates (HR, BP, HR variability, etc) on PK/PD correlation will be examined.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT01404767 on Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 27, 2011)
The amount of time the target heart rate is maintained and the incidence of perioperative hypotension and bradycardia. [ Time Frame: Data will be recorded for 48 hours from arrive to the recovery area ]
Additional assessments include cardiovascular morbidity and mortality including 30-day mortality, myocardial infarction, new cardiac arrhythmia, congestive heart failure, and renal failure, the incidence of post operative delirium, transient ischemic attack, stroke, and length of hospital stay.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Tight Hemodynamic Control in Patients Who Are Chronically on Metoprolol
Official Title  ICMJE Tight Hemodynamic Control in Patients Who Are Chronically on Metoprolol: A Study Comparing the Post Op Continuation of the Preoperative Oral Dose Beta Blockers to Intravenous Esmolol Titrated to a Target Heart Rate (HR)
Brief Summary This study proposes to assess the effect of the standard of care, which is continuation of the pre op beta blocker dose into the post operative period compared to the administration of esmolol titrated to a pre determined target HR. The primary outcome will compare postoperative plasma levels of metoprolol in 2 cohorts in a group who has been continued on metoprolol (administrated via a nasogastric tube in NPO patients) to a group who has been withdrawn from metoprolol but given an esmolol infusion titrated to HR. Secondary outcomes will compare a) the hemodynamic responses, documenting the incidence of unplanned hypotension and bradycardia and b) to compare the effects of Heart rate to the incidence of myocardial ischemia, arrhythmias, delirium and infarction.
Detailed Description The number of high-risk patients undergoing non-cardiac surgery has increased continuously over the last two decades. There is a paucity of data exist about the bioavailability of postoperative administrated beta-blockers. One study reported adequate plasma levels of Propanolol after administration via nasogastric tube but not after oral administration in patient undergoing thyroid surgery.Thus it is possible that patients maintained on oral beta blockers may in fact be experiencing a withdrawal syndrome. Because of the importance of avoiding withdrawal of beta blockers, intravenous administration may be the only alternative in cases where oral administration fails to achieve adequate plasma levels perioperatively. Furthermore, due to changes in pharmacodynamics, intravenous dosage may be the optimal way to achieve tight hemodynamic control. There is, however, no data on the post-operative hemodynamic effects of orally administered beta blockers in patients on chronic beta blockers.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Vascular Disease
  • Hypertension
  • Angina
  • Cardiac Disease
Intervention  ICMJE
  • Drug: Esmolol
    Baseline treatment consists of a bolus of 500ug/kg/min followed by an infusion of 50ug/kg/min for 4 minutes and titrating in increment of 50ug/kg/min up to a maximum of 300ug/kg/min to maintain a HR within 10% of the target HR (≤ 70 bpm), which is 70± 7 bpm.
  • Drug: Metoprolol
    The night and morning before surgery, the patients in the metoprolol arm will receive their standard dose of beta blocker metoprolol.These patients will receive their daily beta blockers orally or via nasogastric tube postoperatively if they are NPO (Group A).
Study Arms  ICMJE
  • Active Comparator: Metoprolol oral dose or Placebo infusion
    Intervention: Drug: Metoprolol
  • Experimental: Esmolol infusion or Placebo oral dose
    Intervention: Drug: Esmolol
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: April 17, 2015)
Original Estimated Enrollment  ICMJE
 (submitted: July 27, 2011)
Actual Study Completion Date  ICMJE December 2013
Actual Primary Completion Date April 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Patient inclusion criteria:

  • Elective vascular surgery
  • Any of the following co morbidities

    • Diabetes
    • Angina
    • Congestive heart failure
    • A serum creatinine above 176 mmol/l
  • All patients must be on stable dose of oral metoprolol (≥ 30 days)
  • Age ≥ 20 years and ≤ 80 years
  • Written informed consent to participate to the study

Patient exclusion criteria:

  • Inability to understand the study protocol
  • Prior gastric surgery or small bowel resection
  • Pacemaker ( since it precludes the measurement of ST changes)
  • Malabsorption syndromes
  • Body Mass Index < 18 and > 35
  • Any patient with suspected of diagnosed Cerebral vascular disease. (We chose to exclude CVA patients due to the ongoing controversy about the increased incidence of stroke in patients have surgery and who are taking beta-blockers.)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 20 Years to 80 Years   (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 Canada
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT01404767
Other Study ID Numbers  ICMJE 10-0713-A
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University Health Network, Toronto
Study Sponsor  ICMJE University Health Network, Toronto
Collaborators  ICMJE Baxter Healthcare Corporation
Investigators  ICMJE
Principal Investigator: Scott Beattie, MD, FRCP University Health Network, Toronto General Hospital
PRS Account University Health Network, Toronto
Verification Date April 2015

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