CAPITAL DOREMI 2: Inotrope Versus Placebo Therapy for Cardiogenic Shock (DOREMI-2)

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.

Study Overview

• Status: Recruiting
• Conditions: Shock, Cardiogenic
• Intervention / Treatment: Drug: Dobutamine; Drug: Milrinone; Drug: Normal Saline

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 Type: Interventional
• Enrollment (Estimated): 346
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Rebecca Mathew, MD; Phone Number: 613-696-7406; Email: rmathew@ottawaheart.ca
• Study Contact Backup: Name: Baylie Morgan, RN; Phone Number: 19059 613-696-7000; Email: bmorgan@ottawaheart.ca

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8L 2X2
      • Recruiting
      • Hamilton Health Sciences
      • Contact: Emilie Belley-Cote, MD; Phone Number: 905-521-2100
      • Principal Investigator: Emilie Belley-Cote, MD
      • Sub-Investigator: Richard Whitlock, MD
      • Sub-Investigator: Craig Ainsworth, MD
      • Sub-Investigator: Faizan Amin, MD
    • Ottawa, Ontario, Canada, K1y4W7
      • Recruiting
      • University of Ottawa Heart Institute
      • Contact: Rebecca Mathew, MD; Phone Number: 613-696-7406; Email: rmathew@ottawaheart.ca
      • Principal Investigator: Rebecca Mathew, MD
      • Sub-Investigator: Pietro Di Santo, MD
• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Not yet recruiting
      • Mayo Clinic
      • Contact: Benjamin M Hibbert, MD, PhD; Email: hibbert.benjamin@mayo.edu
      • Principal Investigator: Benjamin M Hibbert, MD, PhD
      • Sub-Investigator: Jacob C Jentzer, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Adult patients ≥ 18 years of age admitted to an intensive care unit
• SCAI class C or D cardiogenic shock

Exclusion Criteria:

• 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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Inotrope; 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.	Drug: Dobutamine; Dobutamine administered according to its clinical dose stage for cardiogenic shock; Other Names: Dobutrex, Inotrex; Drug: Milrinone; Milrinone administered according to its clinical dose stage for cardiogenic shock
Placebo Comparator: Placebo; 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.	Drug: Normal Saline; Normal saline running at a standardized rate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 minutesLactate greater than 3.5 mmol/L at 6 hours or thereafterNeed for mechanical circulatory support deviceAtrial or ventricular arrhythmia leading to emergent electrical cardioversionResuscitated cardiac arrest	Through duration of hospitalization, up to 12 weeks following admission

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-cause in-hospital mortality	Death resulting from any cause during hospitalization	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	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	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	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)	Through duration of hospitalization, up to 12 weeks following admission
Non-fatal myocardial infarction	Non-fatal myocardial infarction	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	Through duration of hospitalization, up to 12 weeks following admission

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Need for non-invasive or invasive mechanical ventilation	Need for non-invasive or invasive mechanical ventilation after randomization	Through duration of hospitalization, up to 12 weeks following admission
Arrhythmia requiring pharmacologic intervention	Atrial or ventricular arrhythmias requiring initiation of pharmacologic intervention (intravenous or oral anti-arrhythmic therapy)	Through duration of hospitalization, up to 12 weeks following admission
Acute kidney injury	Acute kidney injury	Through duration of hospitalization, up to 12 weeks following admission

Collaborators and Investigators

• Sponsor: Ottawa Heart Institute Research Corporation
• Investigators: Principal Investigator: Rebecca Mathew, MD, Ottawa Heart Institute Research Corporation

Study record dates

Study Major Dates

• Study Start (Actual): March 5, 2022
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: February 3, 2022
• First Submitted That Met QC Criteria: February 23, 2022
• First Posted (Actual): March 4, 2022

Study Record Updates

• Last Update Posted (Actual): May 1, 2026
• Last Update Submitted That Met QC Criteria: April 27, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: shock; cardiogenic; inotrope
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Infarction; Necrosis; Myocardial Ischemia; Myocardial Infarction; Ischemia; Pathological Conditions, Signs and Symptoms; Shock, Cardiogenic; Shock; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pharmaceutical Preparations; Hydrocarbons; Hydrocarbons, Cyclic; Hydrocarbons, Aromatic; Amines; Catechols; Phenols; Benzene Derivatives; Crystalloid Solutions; Isotonic Solutions; Solutions; Phenethylamines; Ethylamines; Aminopyridines; Catecholamines; Amrinone; Milrinone; Dobutamine; Saline Solution
• Other Study ID Numbers: 20210386

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The study data, protocol, SAP, ICF, and CSR will be made available at study completion/publication.
• IPD Sharing Time Frame: Study completion
• IPD Sharing Access Criteria: The above will be made publicly available
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

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