Low Cardiac Output SyndromePhase 4NCT03207165
Milrinone Versus Dobutamine in Critically Ill Patients
A Phase 4 study testing Milrinone and Dobutamine in people with Low Cardiac Output Syndrome and Cardiogenic Shock, run by Ottawa Heart Institute Research Corporation at 1 site in Canada.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Low Cardiac Output Syndrome, Cardiogenic Shock, Acute Coronary Syndrome
- What is being tested?
- Milrinone and Dobutamine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 192 participants
- Where
- 1 siteCanada
- Study dates
- 30 Aug 2017to 12 Jun 2020
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the 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.
- Being tested
- Milrinone, Dobutamine
- Keywords
- Cardiogenic shock, Inotropes, Low cardiac output syndrome
- Medical subject headings
- Cardiac Output, Low, Shock, Cardiogenic, Acute Coronary Syndrome, Pulmonary Edema
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MilrinoneDrug
Also called Mil, Phosphodiesterase-3 inhibitors [PDE3] Inhibitor
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.
DobutamineDrug
Also called Dob, Beta 1/2 Agonist
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.
| Study group | Role | What they receive |
|---|---|---|
| Left ventricular [LV] +/- Biventricular dysfunction | Active comparator | 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. Receives: Drug: Milrinone; Drug: Dobutamine |
| Right ventricular [RV] dysfunction | Active comparator | 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. Receives: Drug: Milrinone; Drug: Dobutamine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Composite Primary End Point
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.
Measured: Through duration of hospitalization, up to 12 weeks following admission
All-cause in-hospital death
All-cause in-hospital death
Measured: Through duration of hospitalization, up to 12 weeks following admission
Non-fatal myocardial infarction [MI]
As defined by Thygesen et al., 2012 (Circulation)
Measured: Through duration of hospitalization, up to 12 weeks following admission
Transient ischemic attack [TIA] or cerebrovascular accident [CVA]
Transient ischemic attack or cerebrovascular accident as diagnosed by a Neurologist either clinically and/or radiographically
Measured: Through duration of hospitalization, up to 12 weeks following admission
Stay in CCU greater than or equal to 7 days
Stay in CCU greater than or equal to 7 days
Measured: Through duration of hospitalization, up to 12 weeks following admission
Acute kidney injury requiring renal replacement therapy
Acute kidney injury requiring renal replacement therapy (intermittent hemodialysis or continuous renal replacement therapy)
Measured: 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
Need for new mechanical support or cardiac transplant
Measured: Through duration of hospitalization, up to 12 weeks following admission
Secondary outcomes (9)
Time on inotropes
Total time on inotropes (in hours)
Measured: Through duration of hospitalization, up to 12 weeks following admission
Non-invasive or invasive mechanical ventilation
Total number of days requiring non-invasive or invasive mechanical ventilation
Measured: Through duration of hospitalization, up to 12 weeks following admission
Change in cardiac index ([CI]
Change in cardiac index measured with PA catheter
Measured: Through duration of hospitalization, up to 12 weeks following admission
Change in pulmonary capillary wedge pressure [PCWP]
Change in pulmonary capillary wedge pressure measured with PA catheter
Measured: Through duration of hospitalization, up to 12 weeks following admission
Change in pulmonary vascular resistance [PVR]
Change in pulmonary vascular resistance measured with PA catheter
Measured: Through duration of hospitalization, up to 12 weeks following admission
Change in systemic vascular resistance [SVR]
Change in systemic vascular resistance measured with PA catheter
Measured: Through duration of hospitalization, up to 12 weeks following admission
Presence of acute kidney injury
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
Measured: Through duration of hospitalization, up to 12 weeks following admission
Serum lactate
Normalization of serum lactate
Measured: Through duration of hospitalization, up to 12 weeks following admission
Arrhythmia requiring medical team intervention
Arrhythmia requiring medical team intervention, either through electrical or chemical cardioversion or any intravenous anti-arrhythmia medication administration
Measured: Through duration of hospitalization, up to 12 weeks following admission
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jul 2017
- Study start30 Aug 2017
- Primary completion12 Jun 2020
- Study completion12 Jun 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Low Cardiac Output SyndromeStudies of the same condition, open and under way.
- 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
- Parallel groups
- 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.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 192 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ottawa Heart Institute Research Corporation
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Benjamin M Hibbert, MD, PhD, Principal investigator, Ottawa Heart Institute Research Corporation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03207165
- Sponsor's protocol ID
- 20160975-01H
- Status last verified
- Jun 2020
- First submitted
- 27 Jun 2017
- Last updated
- 30 Jun 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Abraham WT, Adams KF, Fonarow GC, Costanzo MR, Berkowitz RL, LeJemtel TH, Cheng ML, Wynne J; ADHERE Scientific Advisory Committee and Investigators; ADHERE Study Group. In-hospital mortality in patients with acute decompensated heart failure requiring intravenous vasoactive medications: an analysis from the Acute Decompensated Heart Failure National Registry (ADHERE). J Am Coll Cardiol. 2005 Jul 5;46(1):57-64. doi: 10.1016/j.jacc.2005.03.051.
PubMed 15992636Aranda JM Jr, Schofield RS, Pauly DF, Cleeton TS, Walker TC, Monroe VS Jr, Leach D, Lopez LM, Hill JA. Comparison of dobutamine versus milrinone therapy in hospitalized patients awaiting cardiac transplantation: a prospective, randomized trial. Am Heart J. 2003 Feb;145(2):324-9. doi: 10.1067/mhj.2003.50.
PubMed 12595851Karlsberg RP, DeWood MA, DeMaria AN, Berk MR, Lasher KP. Comparative efficacy of short-term intravenous infusions of milrinone and dobutamine in acute congestive heart failure following acute myocardial infarction. Milrinone-Dobutamine Study Group. Clin Cardiol. 1996 Jan;19(1):21-30. doi: 10.1002/clc.4960190106.
PubMed 8903534King JB, Shah RU, Sainski-Nguyen A, Biskupiak J, Munger MA, Bress AP. Effect of Inpatient Dobutamine versus Milrinone on Out-of-Hospital Mortality in Patients with Acute Decompensated Heart Failure. Pharmacotherapy. 2017 Jun;37(6):662-672. doi: 10.1002/phar.1939.
PubMed 28475215Yamani MH, Haji SA, Starling RC, Kelly L, Albert N, Knack DL, Young JB. Comparison of dobutamine-based and milrinone-based therapy for advanced decompensated congestive heart failure: Hemodynamic efficacy, clinical outcome, and economic impact. Am Heart J. 2001 Dec;142(6):998-1002. doi: 10.1067/mhj.2001.119610.
PubMed 11717603Marbach JA, Di Santo P, Kapur NK, Thayer KL, Simard T, Jung RG, Parlow S, Abdel-Razek O, Fernando SM, Labinaz M, Froeschl M, Mathew R, Hibbert B. Lactate Clearance as a Surrogate for Mortality in Cardiogenic Shock: Insights From the DOREMI Trial. J Am Heart Assoc. 2022 Mar 15;11(6):e023322. doi: 10.1161/JAHA.121.023322. Epub 2022 Mar 9.
PubMed 35261289Jung RG, Di Santo P, Mathew R, Abdel-Razek O, Parlow S, Simard T, Marbach JA, Gillmore T, Mao B, Bernick J, Theriault-Lauzier P, Fu A, Lau L, Motazedian P, Russo JJ, Labinaz M, Hibbert B. Implications of Myocardial Infarction on Management and Outcome in Cardiogenic Shock. J Am Heart Assoc. 2021 Nov 2;10(21):e021570. doi: 10.1161/JAHA.121.021570. Epub 2021 Oct 29.
PubMed 34713704Di Santo P, Mathew R, Jung RG, Simard T, Skanes S, Mao B, Ramirez FD, Marbach JA, Abdel-Razek O, Motazedian P, Parlow S, Boczar KE, D'Egidio G, Hawken S, Bernick J, Wells GA, Dick A, So DY, Glover C, Russo JJ, McGuinty C, Hibbert B; CAPITAL DOREMI investigators. Impact of baseline beta-blocker use on inotrope response and clinical outcomes in cardiogenic shock: a subgroup analysis of the DOREMI trial. Crit Care. 2021 Aug 10;25(1):289. doi: 10.1186/s13054-021-03706-2.
PubMed 34376218Mathew R, Di Santo P, Jung RG, Marbach JA, Hutson J, Simard T, Ramirez FD, Harnett DT, Merdad A, Almufleh A, Weng W, Abdel-Razek O, Fernando SM, Kyeremanteng K, Bernick J, Wells GA, Chan V, Froeschl M, Labinaz M, Le May MR, Russo JJ, Hibbert B. Milrinone as Compared with Dobutamine in the Treatment of Cardiogenic Shock. N Engl J Med. 2021 Aug 5;385(6):516-525. doi: 10.1056/NEJMoa2026845.
PubMed 34347952
Study at a glance
From the registry record, last updated by the sponsor on 30 Jun 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparison of Milrinone Versus Dobutamine in a Heterogeneous Population of Critically Ill Patients
- ClinicalTrials.gov ID
- NCT03207165
- Acronym / sponsor ID
- 20160975-01H
- Keywords
- Cardiogenic shock, Inotropes, Low cardiac output syndrome
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 192 participants (actual)
- Lead sponsor
- Ottawa Heart Institute Research CorporationUniversity, hospital or other
- Study start
- 30 Aug 2017 (actual)
- Primary completion
- 12 Jun 2020 (actual)
- Study completion
- 12 Jun 2020 (actual)
- First posted
- 2 Jul 2017 (actual)
- 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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| Left ventricular [LV] +/- Biventricular dysfunction | Active comparator | Drug: Milrinone, Drug: DobutamineAssessment 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. |
| Right ventricular [RV] dysfunction | Active comparator | Drug: Milrinone, Drug: DobutamineAssessment 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (4 listed)
- 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)
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 |
|---|---|---|
| MilrinoneAlso: Mil, Phosphodiesterase-3 inhibitors [PDE3] InhibitorPatients 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. | Drug | Left ventricular [LV] +/- Biventricular dysfunction, Right ventricular [RV] dysfunction |
| DobutamineAlso: Dob, Beta 1/2 AgonistPatients 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. | Drug | Left ventricular [LV] +/- Biventricular dysfunction, Right ventricular [RV] dysfunction |
Primary outcome
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.
All-cause in-hospital death
Time frame: Through duration of hospitalization, up to 12 weeks following admission
All-cause in-hospital death
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)
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
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
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)
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
9 secondary outcomes
Time on inotropes
Time frame: 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
Change in cardiac index ([CI]
Time frame: 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 vascular resistance [PVR]
Time frame: 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
Presence of acute kidney injury
Time frame: Through duration of hospitalization, up to 12 weeks following admission
Serum lactate
Time frame: 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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jun 2020.
- Background: PubMed 15992636Abraham WT, Adams KF, Fonarow GC, Costanzo MR, Berkowitz RL, LeJemtel TH, Cheng ML, Wynne J; ADHERE Scientific Advisory Committee and Investigators; ADHERE Study Group. In-hospital mortality in patients with acute decompensated heart failure requiring intravenous vasoactive medications: an analysis from the Acute Decompensated Heart Failure National Registry (ADHERE). J Am Coll Cardiol. 2005 Jul 5;46(1):57-64. doi: 10.1016/j.jacc.2005.03.051.
- Background: PubMed 12595851Aranda JM Jr, Schofield RS, Pauly DF, Cleeton TS, Walker TC, Monroe VS Jr, Leach D, Lopez LM, Hill JA. Comparison of dobutamine versus milrinone therapy in hospitalized patients awaiting cardiac transplantation: a prospective, randomized trial. Am Heart J. 2003 Feb;145(2):324-9. doi: 10.1067/mhj.2003.50.
- Background: PubMed 8903534Karlsberg RP, DeWood MA, DeMaria AN, Berk MR, Lasher KP. Comparative efficacy of short-term intravenous infusions of milrinone and dobutamine in acute congestive heart failure following acute myocardial infarction. Milrinone-Dobutamine Study Group. Clin Cardiol. 1996 Jan;19(1):21-30. doi: 10.1002/clc.4960190106.
- Background: PubMed 28475215King JB, Shah RU, Sainski-Nguyen A, Biskupiak J, Munger MA, Bress AP. Effect of Inpatient Dobutamine versus Milrinone on Out-of-Hospital Mortality in Patients with Acute Decompensated Heart Failure. Pharmacotherapy. 2017 Jun;37(6):662-672. doi: 10.1002/phar.1939.
- Background: PubMed 11717603Yamani MH, Haji SA, Starling RC, Kelly L, Albert N, Knack DL, Young JB. Comparison of dobutamine-based and milrinone-based therapy for advanced decompensated congestive heart failure: Hemodynamic efficacy, clinical outcome, and economic impact. Am Heart J. 2001 Dec;142(6):998-1002. doi: 10.1067/mhj.2001.119610.
- Derived from this study: PubMed 35261289Marbach JA, Di Santo P, Kapur NK, Thayer KL, Simard T, Jung RG, Parlow S, Abdel-Razek O, Fernando SM, Labinaz M, Froeschl M, Mathew R, Hibbert B. Lactate Clearance as a Surrogate for Mortality in Cardiogenic Shock: Insights From the DOREMI Trial. J Am Heart Assoc. 2022 Mar 15;11(6):e023322. doi: 10.1161/JAHA.121.023322. Epub 2022 Mar 9.
- Derived from this study: PubMed 34713704Jung RG, Di Santo P, Mathew R, Abdel-Razek O, Parlow S, Simard T, Marbach JA, Gillmore T, Mao B, Bernick J, Theriault-Lauzier P, Fu A, Lau L, Motazedian P, Russo JJ, Labinaz M, Hibbert B. Implications of Myocardial Infarction on Management and Outcome in Cardiogenic Shock. J Am Heart Assoc. 2021 Nov 2;10(21):e021570. doi: 10.1161/JAHA.121.021570. Epub 2021 Oct 29.
- Derived from this study: PubMed 34376218Di Santo P, Mathew R, Jung RG, Simard T, Skanes S, Mao B, Ramirez FD, Marbach JA, Abdel-Razek O, Motazedian P, Parlow S, Boczar KE, D'Egidio G, Hawken S, Bernick J, Wells GA, Dick A, So DY, Glover C, Russo JJ, McGuinty C, Hibbert B; CAPITAL DOREMI investigators. Impact of baseline beta-blocker use on inotrope response and clinical outcomes in cardiogenic shock: a subgroup analysis of the DOREMI trial. Crit Care. 2021 Aug 10;25(1):289. doi: 10.1186/s13054-021-03706-2.
- Derived from this study: PubMed 34347952Mathew R, Di Santo P, Jung RG, Marbach JA, Hutson J, Simard T, Ramirez FD, Harnett DT, Merdad A, Almufleh A, Weng W, Abdel-Razek O, Fernando SM, Kyeremanteng K, Bernick J, Wells GA, Chan V, Froeschl M, Labinaz M, Le May MR, Russo JJ, Hibbert B. Milrinone as Compared with Dobutamine in the Treatment of Cardiogenic Shock. N Engl J Med. 2021 Aug 5;385(6):516-525. doi: 10.1056/NEJMoa2026845.
- Individual participant dataSharing planned: Undecided
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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.
Benjamin M Hibbert, MD, PhD principal investigator
Ottawa Heart Institute Research Corporation
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 Milrinone and Dobutamine in people with Low Cardiac Output Syndrome and Cardiogenic Shock, run by Ottawa Heart Institute Research Corporation 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?
The sponsor lists 6 inclusion and 4 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: finished, as of the sponsor's last update on 30 Jun 2020. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Composite Primary End Point (time frame: Through duration of hospitalization, up to 12 weeks following admission). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03207165, which also lists 9 linked publications.
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 30 Jun 2020.