High-risk, Non-cardiovascular SurgeriesPhase 3NCT01208402
Esmolol for Treatment of Perioperative Tachycardia
A Phase 3 study testing Esmolol in people with High-risk, Non-cardiovascular Surgeries, run by Duke University at 3 sites in United States.
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. Read more about this study
- Who is it for?
- Ages 41 years and older
- Conditions the study is for
- High-risk, Non-cardiovascular Surgeries
- What is being tested?
- Esmolol
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 76 participants
- Where
- 3 sitesUnited States
- Study dates
- Sep 2010to Jul 2013
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 41 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Males or Females
- Age > 40y/o
- Scheduled high risk (ASA II-IV) non-cardiac surgery with anticipated 12 hour post-operative ICU care
- Written informed consent
- Patients on a stable chronic oral beta-blocker therapy
- Revised Cardiac Risk Index 1(below) Cardiac Risk Index 1 or greater (below)
Show all 11Show fewer
- 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
Who cannot join
- Active bleeding
- Untreated left main disease
- Active cardiac condition (eg unstable angina pectoris, acute exacerbation of CHF, serious arrhythmias, symptomatic valve disease)
- Preoperative positive troponin T
- Contraindication for esmolol use
- Previous allergy or intolerance to esmolol
Show all 16Show fewer
- Cancer with an expected life expectancy < 6 months
- Pregnancy or lactating or planning to become pregnant
- Failure to provide informed consent, unable to understand or follow instructions.
- History of drug allergy or idiosyncrasy to beta-adrenergic drugs
- Recent history (within 1 year) of drug or alcohol abuse
- Patients with a Pacemaker
- Abnormal liver function Child-Pugh - B
- Body Mass Index > 45
- Reactive airway disease (defined as a history of hospitalization with status asthmaticus within the past one year)
- Surgery scheduled to begin after 2pm
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Ohio State University
Columbus, Ohio, 43210
Durham VA Medical Center
Durham, North Carolina, 27705
Duke University Medical Center
Durham, North Carolina, 27710
About this study
Official title: Safety and Efficacy of Esmolol for the Treatment of Peri-operative Tachycardia in Patients at Risk for Post Operative Adverse Ischemic Outcomes
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.
Read the detailed 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.
- Conditions
- High-risk, Non-cardiovascular Surgeries
- Being tested
- Esmolol
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EsmololDrug
Also called Brevibloc
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.
| Study group | Role | What they receive |
|---|---|---|
| oral long acting beta blocker | Active comparator | oral administration of long acting beta blocker as standard of care on the day of surgery Receives: Drug: Esmolol |
| Esmolol infusion | Experimental | given 30 minutes prior to induction up to 12 hours post-op Receives: Drug: Esmolol |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Start of surgery to end of surgery, an average duration of 245 minutes
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.
Measured: End of surgery to 3 hours
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.
Measured: Postoperative hours 4-12
Secondary outcomes (3)
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.
Measured: Start of surgery to end of surgery, an average duration of 245 minutes
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.
Measured: end of surgery to 3 hours
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.
Measured: Postoperative hours 4-12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Sep 2010 (estimated)
- Study startSep 2010
- Primary completionJul 2013
- Study completionJul 2013
Why it stopped: Baxter has terminated the study for inadequate enrollment rate accrual.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for High-risk, Non-cardiovascular SurgeriesStudies of the same condition, open and under way.
- More trials run by Duke UniversityThe 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 76 participants (actual)
Sponsor and investigators
- Lead sponsor
- Duke University
- Sponsor type
- University, hospital or other
- Collaborators
- Baxter Healthcare Corporation
- Responsible party
- Sponsor
- Investigators
- Solomon Aronson, MD, Principal investigator, Duke University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01208402
- Sponsor's protocol ID
- Pro00024224
- Status last verified
- Nov 2014
- First submitted
- 10 Sep 2010
- Last updated
- 12 Dec 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Dec 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Efficacy of Esmolol for the Treatment of Peri-operative Tachycardia in Patients at Risk for Post Operative Adverse Ischemic Outcomes
- ClinicalTrials.gov ID
- NCT01208402
- Acronym / sponsor ID
- Pro00024224
- Conditions
- High-risk, Non-cardiovascular Surgeries
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Baxter has terminated the study for inadequate enrollment rate accrual.
- Enrolment
- 76 participants (actual)
- Lead sponsor
- Duke UniversityUniversity, hospital or other
- Collaborators
- Baxter Healthcare Corporation
- Study start
- Sep 2010
- Primary completion
- Jul 2013 (actual)
- Study completion
- Jul 2013 (actual)
- First posted
- 24 Sep 2010 (estimated)
- Results
- Posted 19 Nov 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| oral long acting beta blocker | Active comparator | Drug: Esmololoral administration of long acting beta blocker as standard of care on the day of surgery |
| Esmolol infusion | Experimental | Drug: Esmololgiven 30 minutes prior to induction up to 12 hours post-op |
Who may qualify
- Ages
- 41 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Males or Females
- Age > 40y/o
- Scheduled high risk (ASA II-IV) non-cardiac surgery with anticipated 12 hour post-operative ICU care
- Written informed consent
- Patients on a stable chronic oral beta-blocker therapy
Key exclusion criteria (16 listed)
- Active bleeding
- Untreated left main disease
- Active cardiac condition (eg unstable angina pectoris, acute exacerbation of CHF, serious arrhythmias, symptomatic valve disease)
- Preoperative positive troponin T
- Contraindication for esmolol use
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 |
|---|---|---|
| EsmololAlso: BreviblocInfusion 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. | Drug | Esmolol infusion, oral long acting beta blocker |
Primary outcome
Percentage of Intraoperative Case Time With Heart Rate (HR) <60 or >80 Bpm
Time frame: Start of surgery to end of surgery, an average duration of 245 minutes
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.
Percentage of Postoperative First Three Hours With Heart Rate (HR) <60 or >80 Bpm
Time frame: End of surgery to 3 hours
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.
Percentage of Postoperative Hours 4 to 12 With Heart Rate (HR) <60 or >80 Bpm.
Time frame: Postoperative hours 4-12
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.
3 secondary outcomes
Percentage of Intraoperative Case Time With Systolic Blood Pressure <95 mmHg
Time frame: Start of surgery to end of surgery, an average duration of 245 minutes
Percentage of Postoperative First Three Hours With Systolic Blood Pressure <95 mmHg
Time frame: end of surgery to 3 hours
Percentage of Postoperative Hours 4 to 12 With Systolic Blood Pressure <95 mmHg
Time frame: Postoperative hours 4-12
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Dec 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Solomon Aronson, MD principal investigator
Duke University
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Esmolol in people with High-risk, Non-cardiovascular Surgeries, run by Duke University at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 16 exclusion criteria. 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 12 Dec 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Nov 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Percentage of Intraoperative Case Time With Heart Rate (HR) <60 or >80 Bpm (time frame: Start of surgery to end of surgery, an average duration of 245 minutes). The study lists 3 primary outcomes in all. 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 12 Dec 2014.