Clinical trial NCT03207165: Milrinone Versus Dobutamine in Critically Ill Patients
Official title: Comparison of Milrinone Versus Dobutamine in a Heterogeneous Population of Critically Ill Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Low Cardiac Output Syndrome
Cardiogenic Shock
Acute Coronary Syndrome
Pulmonary Edema
Keywords: Cardiogenic shock
Inotropes
Low cardiac output syndrome
Lead sponsor: Ottawa Heart Institute Research Corporation
Sponsor class: OTHER
First posted: 2017-07-02
Enrollment: 192
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Consecutive patients admitted to the Coronary Care Unit (CCU) at the Ottawa Heart Institute from start of study (tentatively set for August 2017 with anticipated end date of June 2020) and identified by the treating medical team as requiring initiation of inotrope therapy will be screened and randomized based on the healthcare team's clinical assessment of predominantly LV or RV systolic dysfunction (biventricular dysfunction will be assigned to predominantly LV dysfunction). All decisions to initiate inotrope therapy will be made by the primary care team with no involvement from the research team.
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Composite Primary End Point
timeFrame: Through duration of hospitalization, up to 12 weeks following admission
measure: All-cause in-hospital death
timeFrame: Through duration of hospitalization, up to 12 weeks following admission
measure: Non-fatal myocardial infarction [MI]
timeFrame: Through duration of hospitalization, up to 12 weeks following admission
measure: Transient ischemic attack [TIA] or cerebrovascular accident [CVA]
timeFrame: Through duration of hospitalization, up to 12 weeks following admission
measure: Stay in CCU greater than or equal to 7 days
timeFrame: Through duration of hospitalization, up to 12 weeks following admission
measure: Acute kidney injury requiring renal replacement therapy
timeFrame: Through duration of hospitalization, up to 12 weeks following admission
measure: Need for advanced mechanical support [specifically, intra-aortic balloon pump, Impella, ventricular assist device or extra-corporeal membrane oxygenation] or cardiac transplant
timeFrame: Through duration of hospitalization, up to 12 weeks following admission
Secondary outcomes:
measure: Time on inotropes
timeFrame: Through duration of hospitalization, up to 12 weeks following admission
measure: Non-invasive or invasive mechanical ventilation
timeFrame: Through duration of hospitalization, up to 12 weeks following admission
measure: Change in cardiac index ([CI]
timeFrame: Through duration of hospitalization, up to 12 weeks following admission
measure: Change in pulmonary capillary wedge pressure [PCWP]
timeFrame: Through duration of hospitalization, up to 12 weeks following admission
measure: Change in pulmonary vascular resistance [PVR]
timeFrame: Through duration of hospitalization, up to 12 weeks following admission
measure: Change in systemic vascular resistance [SVR]
timeFrame: Through duration of hospitalization, up to 12 weeks following admission
measure: Presence of acute kidney injury
timeFrame: Through duration of hospitalization, up to 12 weeks following admission
measure: Serum lactate
timeFrame: Through duration of hospitalization, up to 12 weeks following admission
measure: Arrhythmia requiring medical team intervention
timeFrame: Through duration of hospitalization, up to 12 weeks following admission
Other outcomes:
measure: Sustained hypotension of systolic BP
timeFrame: Through duration of hospitalization in CCU, up to 12 weeks following admission
measure: Atrial arrhythmias requiring medical intervention
timeFrame: Through duration of hospitalization in CCU, up to 12 weeks following admission
measure: Need for intravenous or oral anti-arrhythmic therapy
timeFrame: Through duration of hospitalization in CCU, up to 12 weeks following admission
measure: Ventricular arrhythmias
timeFrame: Through duration of hospitalization in CCU, up to 12 weeks following admission
measure: Need for up-titration or addition of new vasopressor therapy
timeFrame: Through duration of hospitalization in CCU, up to 12 weeks following admission
Locations:
city: Ottawa
country: Canada
facility: University of Ottawa Heart Institute
state: Ontario
Study officials:
affiliation: Ottawa Heart Institute Research Corporation
name: Benjamin M Hibbert, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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