Tight Hemodynamic Control in Patients Who Are Chronically on Metoprolol

Hypertension Clinical Trial

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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01404767
• Other study ID #: 10-0713-A
• Status: Terminated
• Phase: Phase 4
• First received: June 21, 2011
• Last updated: April 17, 2015
• Start date: April 2011
• Est. completion date: December 2013

Study information

• Verified date: April 2015
• Source: University Health Network, Toronto
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Ethics Review Committee
• Study type: Interventional

Clinical Trial 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who has been continued on metoprolol (administrated via a nasogastric tube in NPO patients) to a group who has been withdrawn from metoprolol but given an esmolol infusion titrated to HR.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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 20
• Est. completion date: December 2013
• Est. primary completion date: April 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years to 80 Years

Eligibility

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.)

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

Related Conditions & MeSH terms

• Angina
• Cardiac Disease
• Heart Diseases
• Hypertension
• Vascular Disease
• Vascular Diseases

Intervention

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.
• 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).

Locations

Country	Name	City	State
Canada	University Heatlh Network, Toronto General Hopsital	Toronto	Ontario

Sponsors (2)

Lead Sponsor	Collaborator
University Health Network, Toronto	Baxter Healthcare Corporation

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The difference between plasma levels of metoprolol within two groups	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.	0,1, 2, 4, 8, 12, 24 hours post intervention	Yes
Secondary	The amount of time the target heart rate is maintained and the incidence of perioperative hypotension and bradycardia.	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.	Data will be recorded for 48 hours from arrive to the recovery area	Yes