Milrinone Versus Dobutamine in Critically Ill Patients

June 29, 2020 updated by: Ottawa Heart Institute Research Corporation

Comparison of Milrinone Versus Dobutamine in a Heterogeneous Population of Critically Ill Patients

The investigators are interested in determining if there is a meaningful difference between two of the most commonly used medications used to improve the pumping function of the heart among critically ill patients admitted to the Coronary Care Unit (CCU) at the University of Ottawa Heart Institute (UOHI). To do this, the investigators will randomly assign patients who are felt to require use of these medications by their treating physicians to one of the two most commonly used agents in Canada: Milrinone or Dobutamine. Each patient will be closely monitored by their healthcare team, and their medication will be adjusted based on each patient's clinical status. Information from blood work (e.g. kidney and liver function, complete blood counts, and other markers of how effectively blood is circulating in the body), assessment of end-organ function (e.g. urine output, mentation), abnormal heart rhythms noted on monitoring and results of imaging studies (e.g. angiogram, echocardiograms.) will be collected for analysis. All patients will be followed for the duration of their hospital stay at UOHI.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

The use of various inotropes in the care of critically ill cardiac patients has become increasingly widespread: while predominantly used in decompensated heart failure, they have also been used in cardiogenic shock complicating acute coronary syndrome (ACS) and septic shock. Purported mechanisms of efficacy include improved cardiac output, improved end-organ perfusion, and vasodilation of both pulmonary and systemic circulations. Two of the most commonly used agents are Milrinone, a phosphodiesterase 3 inhibitor, and Dobutamine, a synthetic catecholamine with affinity for both beta-1 and 2 receptors. Both the American College of Cardiology (ACC) and the European Society of Cardiology (ESC) support inotropes for acute and chronic heart failure management with low cardiac output states. Furthermore, the ACC recommends consideration of inotropic therapy within the STEMI guidelines when ACS is complicated by cardiogenic shock, heart failure or for hemodynamic support in isolated right ventricle infarctions. Beyond primarily cardiac etiologies, inotropes have been identified as first-line additive therapy for cardiac augmentation to Norepinephrine in patients with septic shock complicated by myocardial dysfunction. Despite the lack of convincing data supporting a morbidity or mortality benefit with the use of inotropes in severe, decompensated heart failure, cardiogenic or septic shock, or in ACS, inotropic therapy is still widely used across various critical care settings. Furthermore, to date, there has been no head to head comparison of the two more commonly used positive inotropes: Dobutamine and Milrinone. Selection of one inotrope over another is often guided by physician and center preference, and consideration of and purported avoidance of possible adverse effects. In this pilot study, the investigators aim to describe that characteristics of patients receiving inotropic support in the CCU setting and identify possible differences in morbidity and mortality between Dobutamine and Milrinone among a heterogeneous population of patients admitted to the CCU at UOHI, which may help to inform a larger clinical trial in the future.

The purpose of this pilot study is to: (a) describe the characteristics of patients receiving inotropic support in the coronary care unit (CCU) setting (hemodynamics prior to inotrope initiation, etiology of cardiogenic shock state, use of PA catheter and values if deemed necessary by medical team) and (b) identify possible differences in morbidity [atrial and ventricular arrhythmias, hepatic and renal function, markers of end-organ perfusion (lactate, urine output, mentation status), use of vasopressors, sustained hypotension of systolic blood pressure less than or equal to 90 mmHg for greater than 30 minutes, need for mechanical support, cardiac transplant, total length of CCU stay, length of CCU stay greater than 14 days] and mortality between patients in cardiogenic shock treated with Dobutamine versus Milrinone.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
192

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • Ottawa, Ontario, Canada, K1Y 4W7
        • University of Ottawa Heart Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Have one or more of the following:
  • Low cardiac output state, evidenced by sustained hypotension (systolic blood pressure <90 mmHg) and end organ dysfunction (altered level of consciousness, elevated lactate, renal or hepatic dysfunction)
  • Clinical evidence of systemic and/or pulmonary congestion despite use of vasodilators and/or diuretics
  • ACS complicated by cardiogenic shock (defined as persistent hypotension with systolic blood pressure <90 mmHg with severe reduction in cardiac index [<1.8 L/min/m2 without support or <2.2 L/min/m2 with support], left ventricular end-diastolic pressure >18 mmHg)
  • Augmentation of cardiac output when patient already on maximal vasopressor therapy
  • Or medical team's decision that patient needs inotropic therapy

Exclusion Criteria:

  • Unwillingness or inability to provide informed consent by the patient or substitute decision maker for healthcare decisions
  • Female participants who are currently pregnant
  • Patients presenting with an out-of-hospital cardiac arrest (OOHCA)
  • Healthcare team preference for use of specific inotrope (Milrinone or Dobutamine)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Left ventricular [LV] +/- Biventricular dysfunction
Assessment of left ventricular [LV] or biventricular dysfunction will be based on clinical assessment, available imaging (echocardiogram, left ventriculogram, MUGA/RNA scan, cardiac MRI, etc.) and known past medical history (if available and contributory). Patients identified as having biventricular dysfunction will be randomized within the LV dysfunction arm of the trial. Patients in this arm will be randomized in a 1:1 fashion to Milrinone or Dobutamine.
Drug: Milrinone
Patients will be initiated on Milrinone at 0.125 mcg/kg/min [stage 1] and will be titrated according to a blinded protocol from stages 2 to 5 [0.250, 0.375, 0.5 and >0.5 ug/kg/min]. All orders to initiate and titrate the dose of the allocated inotrope will be written in the chart as follows: 'Study inotrope dose to be [increased/decreased/maintained] at stage [1-5]' so as to ensure that treating physicians remain blinded to the allocated drug.
Other Names:
  • Mil
  • Phosphodiesterase-3 inhibitors [PDE3] Inhibitor
Drug: Dobutamine
Patients will be initiated on Dobutamine at 2.5 mcg/kg/min [stage 1] and will be titrated according to a blinded protocol from stages 2 to 5 [5.0, 7.5, 10 and >10 ug/kg/min]. All orders to initiate and titrate the dose of the allocated inotrope will be written in the chart as follows: 'Study inotrope dose to be [increased/decreased/maintained] at stage [1-5]' so as to ensure that treating physicians remain blinded to the allocated drug.
Other Names:
  • Dob
  • Beta 1/2 Agonist
Active Comparator: Right ventricular [RV] dysfunction
Assessment of right ventricular [RV] dysfunction will be based on clinical assessment, available imaging (echocardiogram, left ventriculogram, MUGA/RNA scan, cardiac MRI, etc.) and known past medical history (if available and contributory). Patients in this arm will be randomized in a 1:1 fashion to Milrinone or Dobutamine.
Drug: Milrinone
Patients will be initiated on Milrinone at 0.125 mcg/kg/min [stage 1] and will be titrated according to a blinded protocol from stages 2 to 5 [0.250, 0.375, 0.5 and >0.5 ug/kg/min]. All orders to initiate and titrate the dose of the allocated inotrope will be written in the chart as follows: 'Study inotrope dose to be [increased/decreased/maintained] at stage [1-5]' so as to ensure that treating physicians remain blinded to the allocated drug.
Other Names:
  • Mil
  • Phosphodiesterase-3 inhibitors [PDE3] Inhibitor
Drug: Dobutamine
Patients will be initiated on Dobutamine at 2.5 mcg/kg/min [stage 1] and will be titrated according to a blinded protocol from stages 2 to 5 [5.0, 7.5, 10 and >10 ug/kg/min]. All orders to initiate and titrate the dose of the allocated inotrope will be written in the chart as follows: 'Study inotrope dose to be [increased/decreased/maintained] at stage [1-5]' so as to ensure that treating physicians remain blinded to the allocated drug.
Other Names:
  • Dob
  • Beta 1/2 Agonist

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Composite Primary End Point
Time Frame: Through duration of hospitalization, up to 12 weeks following admission
Composite of all-cause in-hospital death, non-fatal MI, TIA or CVA diagnosed by a Neurologist, renal failure requiring renal replacement therapy, need for cardiac transplant or new mechanical support, any atrial or ventricular arrhythmia leading to cardiac arrest and resuscitation.
Through duration of hospitalization, up to 12 weeks following admission
All-cause in-hospital death
Time Frame: Through duration of hospitalization, up to 12 weeks following admission
All-cause in-hospital death
Through duration of hospitalization, up to 12 weeks following admission
Non-fatal myocardial infarction [MI]
Time Frame: Through duration of hospitalization, up to 12 weeks following admission
As defined by Thygesen et al., 2012 (Circulation)
Through duration of hospitalization, up to 12 weeks following admission
Transient ischemic attack [TIA] or cerebrovascular accident [CVA]
Time Frame: Through duration of hospitalization, up to 12 weeks following admission
Transient ischemic attack or cerebrovascular accident as diagnosed by a Neurologist either clinically and/or radiographically
Through duration of hospitalization, up to 12 weeks following admission
Stay in CCU greater than or equal to 7 days
Time Frame: Through duration of hospitalization, up to 12 weeks following admission
Stay in CCU greater than or equal to 7 days
Through duration of hospitalization, up to 12 weeks following admission
Acute kidney injury requiring renal replacement therapy
Time Frame: Through duration of hospitalization, up to 12 weeks following admission
Acute kidney injury requiring renal replacement therapy (intermittent hemodialysis or continuous renal replacement therapy)
Through duration of hospitalization, up to 12 weeks following admission
Need for advanced mechanical support [specifically, intra-aortic balloon pump, Impella, ventricular assist device or extra-corporeal membrane oxygenation] or cardiac transplant
Time Frame: Through duration of hospitalization, up to 12 weeks following admission
Need for new mechanical support or cardiac transplant
Through duration of hospitalization, up to 12 weeks following admission

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Time on inotropes
Time Frame: Through duration of hospitalization, up to 12 weeks following admission
Total time on inotropes (in hours)
Through duration of hospitalization, up to 12 weeks following admission
Non-invasive or invasive mechanical ventilation
Time Frame: Through duration of hospitalization, up to 12 weeks following admission
Total number of days requiring non-invasive or invasive mechanical ventilation
Through duration of hospitalization, up to 12 weeks following admission
Change in cardiac index ([CI]
Time Frame: Through duration of hospitalization, up to 12 weeks following admission
Change in cardiac index measured with PA catheter
Through duration of hospitalization, up to 12 weeks following admission
Change in pulmonary capillary wedge pressure [PCWP]
Time Frame: Through duration of hospitalization, up to 12 weeks following admission
Change in pulmonary capillary wedge pressure measured with PA catheter
Through duration of hospitalization, up to 12 weeks following admission
Change in pulmonary vascular resistance [PVR]
Time Frame: Through duration of hospitalization, up to 12 weeks following admission
Change in pulmonary vascular resistance measured with PA catheter
Through duration of hospitalization, up to 12 weeks following admission
Change in systemic vascular resistance [SVR]
Time Frame: Through duration of hospitalization, up to 12 weeks following admission
Change in systemic vascular resistance measured with PA catheter
Through duration of hospitalization, up to 12 weeks following admission
Presence of acute kidney injury
Time Frame: Through duration of hospitalization, up to 12 weeks following admission
Presence of acute kidney injury (defined by KDIGO as creatinine increased by 26.5 umol/L, 1.5 times baseline within prior 7 days, or urine volume <0.5 mL/kg/hour for greater than or equal to 6 hours
Through duration of hospitalization, up to 12 weeks following admission
Serum lactate
Time Frame: Through duration of hospitalization, up to 12 weeks following admission
Normalization of serum lactate
Through duration of hospitalization, up to 12 weeks following admission
Arrhythmia requiring medical team intervention
Time Frame: Through duration of hospitalization, up to 12 weeks following admission
Arrhythmia requiring medical team intervention, either through electrical or chemical cardioversion or any intravenous anti-arrhythmia medication administration
Through duration of hospitalization, up to 12 weeks following admission

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Sustained hypotension of systolic BP
Time Frame: Through duration of hospitalization in CCU, up to 12 weeks following admission
Sustained systolic blood pressure hypotension of less than or equal to 90 mmHg for greater than or equal to 30 minutes (or requiring medical intervention)
Through duration of hospitalization in CCU, up to 12 weeks following admission
Atrial arrhythmias requiring medical intervention
Time Frame: Through duration of hospitalization in CCU, up to 12 weeks following admission
Atrial flutter, fibrillation or tachycardia requiring medical intervention
Through duration of hospitalization in CCU, up to 12 weeks following admission
Need for intravenous or oral anti-arrhythmic therapy
Time Frame: Through duration of hospitalization in CCU, up to 12 weeks following admission
Initiation of intravenous or oral anti-arrhythmic therapy
Through duration of hospitalization in CCU, up to 12 weeks following admission
Ventricular arrhythmias
Time Frame: Through duration of hospitalization in CCU, up to 12 weeks following admission
Ventricular arrhythmias (monomorphic or polymorphic ventricular tachycardia [VT] greater than 30 seconds or hemodynamically unstable ventricular arrhythmia requiring intervention, or VF)
Through duration of hospitalization in CCU, up to 12 weeks following admission
Need for up-titration or addition of new vasopressor therapy
Time Frame: Through duration of hospitalization in CCU, up to 12 weeks following admission
Need for up-titration or addition of new vasopressor therapy
Through duration of hospitalization in CCU, up to 12 weeks following admission

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Ottawa Heart Institute Research Corporation

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Benjamin M Hibbert, MD, PhD, Ottawa Heart Institute Research Corporation

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 30, 2017

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 12, 2020

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 12, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 27, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 30, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 2, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 30, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 29, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 20160975-01H

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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