Shock, CardiogenicPhase 4DOREMI-2NCT05267886
CAPITAL DOREMI 2: Inotrope Versus Placebo Therapy for Cardiogenic Shock
A Phase 4 study testing Dobutamine, Milrinone and Normal Saline in people with Shock, Cardiogenic, run by Ottawa Heart Institute Research Corporation at 3 sites in 2 countries.
Trial summary
The investigators are interested in determining if there is a meaningful benefit from the use of medications purported to increase the pumping function of the heart (i.e. inotropes) among critically ill patients admitted to the Cardiac Intensive Care Unit (CICU). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Shock, Cardiogenic
- What is being tested?
- Dobutamine, Milrinone and Normal Saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 346 participants
- Where
- 3 sitesin 2 countries
- Study dates
- 5 Mar 2022to Dec 2026
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
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
- Adult patients ≥ 18 years of age admitted to an intensive care unit
- SCAI class C or D cardiogenic shock
Who cannot join
- Unwilling or unable to obtain informed consent by the participant or substitute decision maker
- Patients who are currently pregnant or breast-feeding
- Patients presenting with an out-of-hospital cardiac arrest (OHCA)
- Administration of milrinone or dobutamine in the 24 hours preceding anticipated randomization
- Severe obstructive valvular lesions, including aortic stenosis and/or mitral stenosis
- Dynamic left ventricular outflow tract obstruction
Trial locations and contacts
3 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
3 sites in 2 countries
Canada2 sites, 2 recruiting
- Recruiting
Hamilton Health Sciences
Hamilton, Ontario, L8L 2X2
Emilie Belley-Cote, MD, 905-521-2100
Emilie Belley-Cote, MD
- Recruiting
University of Ottawa Heart Institute
Ottawa, Ontario, K1Y4W7
Rebecca Mathew, MD, 613-696-7406, rmathew@ottawaheart.ca
Rebecca Mathew, MD
United States1 site, 1 recruiting
- Not yet recruiting
Mayo Clinic
Rochester, Minnesota, 55905
Benjamin M Hibbert, MD, PhD, hibbert.benjamin@mayo.edu
Benjamin M Hibbert, MD, PhD
About this study
The investigators are interested in determining if there is a meaningful benefit from the use of medications purported to increase the pumping function of the heart (i.e. inotropes) among critically ill patients admitted to the Cardiac Intensive Care Unit (CICU). To do this, the investigators will conduct a multi-centre, double blind, randomized control trial with patients who are deemed to require these medications by their treating physician to one of the two most commonly used agents in Canada (Milrinone or Dobutamine) or placebo. Each patient will be closely monitored by their healthcare team. The dose of medication will be adjusted according to each patients' clinical status. After 12 hours, the participants will move to open label treatment and any continued use of inotropes will be at the discretion of their treating physician.
Read the detailed description
Cardiogenic shock (CS) is a state of inadequate end-organ perfusion due to cardiac dysfunction. Acute myocardial infarction (AMI) remains the most prevalent cause of CS, with mortality reaching upwards of 40% despite advances in emergent revascularization and accelerating use of mechanical circulatory support devices. International guidelines support the use of vasopressors and inotropes as a mainstay of medical therapy among this cohort of critically ill patients. Recently, the first head-to-head prospective randomized trial (CAPITAL DOREMI) comparing milrinone and dobutamine in a cohort of CS participants was performed and found no difference between agents.
There is a signal of harm associated with the use of inotropes in both acute, decompensated heart failure and in the longitudinal management of chronic heart failure. Inotrope use has also been associated with longer ICU and in-hospital length of stay, as well as higher in-hospital mortality. A recent network meta-analysis on treatment strategies in CS and found that while milrinone and dobutamine may reduce the risk of mortality compared to placebo, the evidence is of low certainty and the wide confidence intervals do not rule out the possibility of harm.
Despite their frequent use in the management of patients with CS, it remains unknown if inotropes are needed to augment successful initial resuscitation, reduce morbidity and mortality, or if they cause potential harm in this already critically ill patient population.
This study is a multi-centre, double blind, randomized controlled trial designed to examine the efficacy and safety of inotrope therapy against placebo in the initial resuscitation of SCAI class C to D cardiogenic shock. Consecutive patients admitted to an intensive care unit will be identified by the treating medical team as requiring new initiation of inotrope therapy for CS. All decisions to initiate inotrope therapy will be made by the primary care team with no involvement from the research team. The study hypothesis is that inotrope therapy will lead to an overall improvement in the primary outcome as compared to placebo.
- Conditions
- Shock, Cardiogenic
- Being tested
- Dobutamine, Milrinone, Normal Saline
- Keywords
- cardiogenic, shock, inotrope
- Medical subject headings
- Shock, Cardiogenic, Shock
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DobutamineDrug
Also called Dobutrex, Inotrex
Dobutamine administered according to its clinical dose stage for cardiogenic shock
MilrinoneDrug
Milrinone administered according to its clinical dose stage for cardiogenic shock
Normal SalineDrug
Normal saline running at a standardized rate
| Study group | Role | What they receive |
|---|---|---|
| Inotrope | Active comparator | Participants randomized to receive the inotrope will be initiated on inotrope therapy at starting doses and titrated according to standard clinical care. During reassessment, the treating physicians will make a decision about adjustment of the inotrope dose (increase, maintain or decrease) based on hemodynamics, end-organ perfusion, vasopressor support and clinical exam. Dobutamine doses will be 2.5, 5.0, 7.5, 10 and >10 ug/kg/min and milrinone doses will be 0.125, 0.250, 0.375, 0.5 and >0.5 ug/kg/min. These dose stages are identical to those used in Capital Do-Re-Mi and reflect current standard of care. Receives: Drug: Dobutamine; Drug: Milrinone |
| Placebo | Placebo comparator | Participants in the placebo arm will have an intravenous solution of 0.9% NaCl running at a standardized rate, comparable to the infusion rate of the inotrope arm. Receives: Drug: Normal Saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Primary composite outcome
The primary outcome will be a composite of:
- All-cause mortality during the hospitalization
- Measured within the first 12 hours of starting the study intervention, any of:
- Sustained hypotension (mean arterial pressure ≤55mmHg) or sustained requirement of high dose vasopressors (norepinephrine >0.2 mcg/kg/min or norepinephrine 0.2 mcg/kg/min plus any additional agent) with any escalation in dose from time of randomization, for >/= 60 minutes
- Lactate greater than 3.5 mmol/L at 6 hours or thereafter
- Need for mechanical circulatory support device
- Atrial or ventricular arrhythmia leading to emergent electrical cardioversion
- Resuscitated cardiac arrest
Measured: Through duration of hospitalization, up to 12 weeks following admission
Secondary outcomes (7)
All-cause in-hospital mortality
Death resulting from any cause during hospitalization
Measured: Through duration of hospitalization, up to 12 weeks following admission
Renal failure requiring new initiation of renal replacement therapy
Requiring new initiation of renal replacement therapy
Measured: Through duration of hospitalization, up to 12 weeks following admission
Need for cardiac transplant or mechanical circulatory support
Identification of needing a cardiac transplant or mechanical circulatory support
Measured: Through duration of hospitalization, up to 12 weeks following admission
Atrial or ventricular arrhythmia leading to emergent electrical cardioversion
Requiring emergent electrical cardioversion for atrial or ventricular arrhythmia
Measured: Through duration of hospitalization, up to 12 weeks following admission
Resuscitated cardiac arrest
Cardiopulmonary arrest requiring chest compressions and/or defibrillation with successful return of spontaneous circulation (ROSC)
Measured: Through duration of hospitalization, up to 12 weeks following admission
Non-fatal myocardial infarction
Non-fatal myocardial infarction
Measured: Through duration of hospitalization, up to 12 weeks following admission
Stroke or transient ischemic attack
Defined as an episode of focal or global neurological deficit as diagnosed by a neurologist
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 posted4 Mar 2022
- Study start5 Mar 2022
- Primary completionDec 2026 (estimated)
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Shock, CardiogenicStudies of the same condition, open and under way.
- More trials run by Ottawa Heart Institute Research CorporationThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Parallel randomized control trial
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 346 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ottawa Heart Institute Research Corporation
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Rebecca Mathew, MD, Principal investigator, Ottawa Heart Institute Research Corporation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05267886
- Sponsor's protocol ID
- 20210386
- Acronym
- DOREMI-2
- Status last verified
- Mar 2026
- First submitted
- 3 Feb 2022
- Last updated
- 1 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The study data, protocol, SAP, ICF, and CSR will be made available at study completion/publication.
Study at a glance
From the registry record, last updated by the sponsor on 1 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- CAPITAL DOREMI 2: Inotrope Versus Placebo Therapy for Cardiogenic Shock
- ClinicalTrials.gov ID
- NCT05267886
- Acronym / sponsor ID
- DOREMI-2 / 20210386
- Conditions
- Shock, Cardiogenic
- Keywords
- cardiogenic, shock, inotrope
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 346 participants (estimated)
- Lead sponsor
- Ottawa Heart Institute Research CorporationUniversity, hospital or other
- Study start
- 5 Mar 2022 (actual)
- Primary completion
- Dec 2026 (estimated)
- Study completion
- Dec 2026 (estimated)
- First posted
- 4 Mar 2022 (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 benefit from the use of medications purported to increase the pumping function of the heart (i.e. inotropes) among critically ill patients admitted to the Cardiac Intensive Care Unit (CICU). To do this, the investigators will conduct a multi-centre, double blind, randomized control trial with patients who are deemed to require these medications by their treating physician to one of the two most commonly used agents in Canada (Milrinone or Dobutamine) or placebo. Each patient will be closely monitored by their healthcare team. The dose of medication will be adjusted according to each patients' clinical status. After 12 hours, the participants will move to open label treatment and any continued use of inotropes will be at the discretion of their treating physician.
Detailed description
Cardiogenic shock (CS) is a state of inadequate end-organ perfusion due to cardiac dysfunction. Acute myocardial infarction (AMI) remains the most prevalent cause of CS, with mortality reaching upwards of 40% despite advances in emergent revascularization and accelerating use of mechanical circulatory support devices. International guidelines support the use of vasopressors and inotropes as a mainstay of medical therapy among this cohort of critically ill patients. Recently, the first head-to-head prospective randomized trial (CAPITAL DOREMI) comparing milrinone and dobutamine in a cohort of CS participants was performed and found no difference between agents.
There is a signal of harm associated with the use of inotropes in both acute, decompensated heart failure and in the longitudinal management of chronic heart failure. Inotrope use has also been associated with longer ICU and in-hospital length of stay, as well as higher in-hospital mortality. A recent network meta-analysis on treatment strategies in CS and found that while milrinone and dobutamine may reduce the risk of mortality compared to placebo, the evidence is of low certainty and the wide confidence intervals do not rule out the possibility of harm.
Despite their frequent use in the management of patients with CS, it remains unknown if inotropes are needed to augment successful initial resuscitation, reduce morbidity and mortality, or if they cause potential harm in this already critically ill patient population.
This study is a multi-centre, double blind, randomized controlled trial designed to examine the efficacy and safety of inotrope therapy against placebo in the initial resuscitation of SCAI class C to D cardiogenic shock. Consecutive patients admitted to an intensive care unit will be identified by the treating medical team as requiring new initiation of inotrope therapy for CS. All decisions to initiate inotrope therapy will be made by the primary care team with no involvement from the research team. The study hypothesis is that inotrope therapy will lead to an overall improvement in the primary outcome as compared to placebo.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- Model description
- Parallel randomized control trial
| Arm | Type | Receives |
|---|---|---|
| Inotrope | Active comparator | Drug: Dobutamine, Drug: MilrinoneParticipants randomized to receive the inotrope will be initiated on inotrope therapy at starting doses and titrated according to standard clinical care. During reassessment, the treating physicians will make a decision about adjustment of the inotrope dose (increase, maintain or decrease) based on hemodynamics, end-organ perfusion, vasopressor support and clinical exam. Dobutamine doses will be 2.5, 5.0, 7.5, 10 and >10 ug/kg/min and milrinone doses will be 0.125, 0.250, 0.375, 0.5 and >0.5 ug/kg/min. These dose stages are identical to those used in Capital Do-Re-Mi and reflect current standard of care. |
| Placebo | Placebo comparator | Drug: Normal SalineParticipants in the placebo arm will have an intravenous solution of 0.9% NaCl running at a standardized rate, comparable to the infusion rate of the inotrope arm. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Adult patients ≥ 18 years of age admitted to an intensive care unit
- SCAI class C or D cardiogenic shock
Key exclusion criteria (6 listed)
- Unwilling or unable to obtain informed consent by the participant or substitute decision maker
- Patients who are currently pregnant or breast-feeding
- Patients presenting with an out-of-hospital cardiac arrest (OHCA)
- Administration of milrinone or dobutamine in the 24 hours preceding anticipated randomization
- Severe obstructive valvular lesions, including aortic stenosis and/or mitral stenosis
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 |
|---|---|---|
| DobutamineAlso: Dobutrex, InotrexDobutamine administered according to its clinical dose stage for cardiogenic shock | Drug | Inotrope |
| MilrinoneMilrinone administered according to its clinical dose stage for cardiogenic shock | Drug | Inotrope |
| Normal SalineNormal saline running at a standardized rate | Drug | Placebo |
Primary outcome
Primary composite outcome
Time frame: Through duration of hospitalization, up to 12 weeks following admission
The primary outcome will be a composite of: 1. All-cause mortality during the hospitalization 2. Measured within the first 12 hours of starting the study intervention, any of: 1. Sustained hypotension (mean arterial pressure ≤55mmHg) or sustained requirement of high dose vasopressors (norepinephrine >0.2 mcg/kg/min or norepinephrine 0.2 mcg/kg/min plus any additional agent) with any escalation in dose from time of randomization, for >/= 60 minutes 2. Lactate greater than 3.5 mmol/L at 6 hours or thereafter 3. Need for mechanical circulatory support device 4. Atrial or ventricular arrhythmia leading to emergent electrical cardioversion 5. Resuscitated cardiac arrest
7 secondary outcomes
All-cause in-hospital mortality
Time frame: Through duration of hospitalization, up to 12 weeks following admission
Renal failure requiring new initiation of renal replacement therapy
Time frame: Through duration of hospitalization, up to 12 weeks following admission
Need for cardiac transplant or mechanical circulatory support
Time frame: Through duration of hospitalization, up to 12 weeks following admission
Atrial or ventricular arrhythmia leading to emergent electrical cardioversion
Time frame: Through duration of hospitalization, up to 12 weeks following admission
Resuscitated cardiac arrest
Time frame: Through duration of hospitalization, up to 12 weeks following admission
Non-fatal myocardial infarction
Time frame: Through duration of hospitalization, up to 12 weeks following admission
Stroke or transient ischemic attack
Time frame: Through duration of hospitalization, up to 12 weeks following admission
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 May 2026.
- Individual participant dataSharing planned: Yes. The study data, protocol, SAP, ICF, and CSR will be made available at study completion/publication.
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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.
Rebecca Mathew, MD principal investigator
Ottawa Heart Institute Research Corporation
3 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Dobutamine, Milrinone and Normal Saline in people with Shock, Cardiogenic, run by Ottawa Heart Institute Research Corporation at 3 sites in 2 countries.
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 2 inclusion and 6 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: looking for participants now, as of the sponsor's last update on 1 May 2026. 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 Canada, 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. Some participants in this study may receive a placebo. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Rebecca Mathew, MD (613-696-7406, rmathew@ottawaheart.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Primary composite outcome (time frame: Through duration of hospitalization, up to 12 weeks following admission). 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 1 May 2026.