Vascular DiseasePhase 4NCT01404767
Tight Hemodynamic Control in Patients Who Are Chronically on Metoprolol
A Phase 4 study testing Esmolol and Metoprolol in people with Vascular Disease and Hypertension, run by University Health Network, Toronto at 1 site in Canada.
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. Read more about this study
- Who is it for?
- Ages 20 to 80 years
- Conditions the study is for
- Vascular Disease, Hypertension, Angina
- What is being tested?
- Esmolol and Metoprolol
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteCanada
- Study dates
- Apr 2011to Dec 2013
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
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.)
Trial locations and contacts
1 site in 1 country.
Canada1 site
University Heatlh Network, Toronto General Hopsital
Toronto, Ontario, M5G 2C4
About this study
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)
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.
Read the 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.
- Conditions
- Vascular Disease, Hypertension, Angina, Cardiac Disease
- Being tested
- Esmolol, Metoprolol
- Keywords
- Vascular surgery, esmolol, hemodynamic control
- Medical subject headings
- Vascular Diseases, Hypertension, Angina Pectoris, Heart Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EsmololDrug
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.
MetoprololDrug
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 group | Role | What they receive |
|---|---|---|
| Metoprolol oral dose or Placebo infusion | Active comparator | Not described Receives: Drug: Metoprolol |
| Esmolol infusion or Placebo oral dose | Experimental | Not described Receives: Drug: Esmolol |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 0,1, 2, 4, 8, 12, 24 hours post intervention
Secondary outcomes (1)
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.
Measured: Data will be recorded for 48 hours from arrive to the recovery area
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jul 2011 (estimated)
- Study startApr 2011
- Primary completionApr 2011
- Study completionDec 2013
Why it stopped: Enrollment slow over 2 years a change in the population less on metoprolol than initially anticipated
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Vascular DiseaseStudies of the same condition, open and under way.
- More trials run by University Health Network, TorontoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Health Network, Toronto
- Sponsor type
- University, hospital or other
- Collaborators
- Baxter Healthcare Corporation
- Responsible party
- Sponsor
- Investigators
- Scott Beattie, MD, FRCP, Principal investigator, University Health Network, Toronto General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01404767
- Sponsor's protocol ID
- 10-0713-A
- Status last verified
- Apr 2015
- First submitted
- 21 Jun 2011
- Last updated
- 21 Apr 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 21 Apr 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT01404767
- Acronym / sponsor ID
- 10-0713-A
- Conditions
- Vascular Disease, Hypertension, Angina, Cardiac Disease
- Keywords
- Vascular surgery, esmolol, hemodynamic control
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Enrollment slow over 2 years a change in the population less on metoprolol than initially anticipated
- Enrolment
- 20 participants (actual)
- Lead sponsor
- University Health Network, TorontoUniversity, hospital or other
- Collaborators
- Baxter Healthcare Corporation
- Study start
- Apr 2011
- Primary completion
- Apr 2011 (actual)
- Study completion
- Dec 2013 (actual)
- First posted
- 28 Jul 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Metoprolol oral dose or Placebo infusion | Active comparator | Drug: Metoprolol |
| Esmolol infusion or Placebo oral dose | Experimental | Drug: Esmolol |
Who may qualify
- Ages
- 20 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EsmololBaseline 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 | Esmolol infusion or Placebo oral dose |
| MetoprololThe 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). | Drug | Metoprolol oral dose or Placebo infusion |
Primary outcome
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.
1 secondary outcome
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
Results and safety
The study was stopped early (reason given: Enrollment slow over 2 years a change in the population less on metoprolol than initially anticipated). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Apr 2015.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Scott Beattie, MD, FRCP principal investigator
University Health Network, Toronto General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Esmolol and Metoprolol in people with Vascular Disease and Hypertension, run by University Health Network, Toronto at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 21 Apr 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Enrollment slow over 2 years a change in the population less on metoprolol than initially anticipated). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The difference between plasma levels of metoprolol within two groups (time frame: 0,1, 2, 4, 8, 12, 24 hours post intervention). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Apr 2015.