CAPITAL DOREMI 2: Inotrope Versus Placebo Therapy for Cardiogenic Shock

Shock, Cardiogenic Clinical Trial

— DOREMI-2  

Official title:

CAPITAL DOREMI 2: Inotrope Versus Placebo Therapy for Cardiogenic Shock

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05267886
• Other study ID #: 20210386
• Status: Recruiting
• Phase: Phase 4
• Start date: March 5, 2022
• Est. completion date: December 2026

Study information

• Verified date: April 2024
• Source: Ottawa Heart Institute Research Corporation
• Contact: Rebecca Mathew, MD
• Phone: 613-696-7406
• Email: rmathew[@]ottawaheart.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical 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). 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 346
• Est. completion date: December 2026
• Est. primary completion date: January 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Shock
• Shock, Cardiogenic

Intervention

Drug:
• Dobutamine
Dobutamine administered according to its clinical dose stage for cardiogenic shock
• Milrinone
Milrinone administered according to its clinical dose stage for cardiogenic shock
• Normal Saline
Normal saline running at a standardized rate

Locations

Country	Name	City	State
Canada	Hamilton Health Sciences	Hamilton	Ontario
Canada	University of Ottawa Heart Institute	Ottawa	Ontario
United States	Mayo Clinic	Rochester	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Ottawa Heart Institute Research Corporation

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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
Other	Acute kidney injury	Acute kidney injury	Through duration of hospitalization, up to 12 weeks following admission
Primary	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	Through duration of hospitalization, up to 12 weeks following admission
Secondary	All-cause in-hospital mortality	Death resulting from any cause during hospitalization	Through duration of hospitalization, up to 12 weeks following admission
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Non-fatal myocardial infarction	Non-fatal myocardial infarction	Through duration of hospitalization, up to 12 weeks following admission
Secondary	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