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Tight Hemodynamic Control in Patients Who Are Chronically on Metoprolol

This study has been terminated.
(Enrollment slow over 2 years a change in the population less on metoprolol than initially anticipated)
Sponsor:
Collaborator:
Baxter Healthcare Corporation
Information provided by (Responsible Party):
University Health Network, Toronto
ClinicalTrials.gov Identifier:
NCT01404767
First received: June 21, 2011
Last updated: April 17, 2015
Last verified: April 2015
History of Changes
  Purpose
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who has been continued on metoprolol (administrated via a nasogastric tube in NPO patients) to a group who has been withdrawn from metoprolol but given an esmolol infusion titrated to HR.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.

Condition Intervention Phase
Vascular Disease
Hypertension
Angina
Cardiac Disease
 Drug: Esmolol
Drug: Metoprolol
 Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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)

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by University Health Network, Toronto:

Primary Outcome Measures:
  • The difference between plasma levels of metoprolol within two groups [ Time Frame: 0,1, 2, 4, 8, 12, 24 hours post intervention ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
    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.
Enrollment: 20
Study Start Date: April 2011
Study Completion Date: December 2013
Primary Completion Date: April 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Metoprolol oral dose or Placebo infusion 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).
Experimental: Esmolol infusion or Placebo oral dose 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.

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.
  Eligibility
Ages Eligible for Study:   20 Years to 80 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.)
  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: NCT01404767

Locations
Canada, Ontario
University Heatlh Network, Toronto General Hopsital
Toronto, Ontario, Canada, M5G 2C4
Sponsors and Collaborators
University Health Network, Toronto
Baxter Healthcare Corporation
Investigators
Principal Investigator: Scott Beattie, MD, FRCP University Health Network, Toronto General Hospital
  More Information

Responsible Party: University Health Network, Toronto
ClinicalTrials.gov Identifier: NCT01404767     History of Changes
Other Study ID Numbers: 10-0713-A 
Study First Received: June 21, 2011
Last Updated: April 17, 2015
Health Authority: Canada: Ethics Review Committee

Keywords provided by University Health Network, Toronto:
Vascular surgery
esmolol
hemodynamic control

Additional relevant MeSH terms:
Vascular Diseases
Heart Diseases
Cardiovascular Diseases
Metoprolol
Esmolol
Anti-Arrhythmia Agents
Antihypertensive Agents
Sympatholytics
Autonomic Agents
 Peripheral Nervous System Agents
Physiological Effects of Drugs
Adrenergic beta-1 Receptor Antagonists
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 23, 2016