Clinical trial NCT05267886: CAPITAL DOREMI 2: Inotrope Versus Placebo Therapy for Cardiogenic Shock
Official title: CAPITAL DOREMI 2: Inotrope Versus Placebo Therapy for Cardiogenic Shock
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Shock, Cardiogenic
Keywords: cardiogenic
shock
inotrope
Lead sponsor: Ottawa Heart Institute Research Corporation
Sponsor class: OTHER
First posted: 2022-03-04
Enrollment: 346
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Parallel randomized control trial
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Primary composite outcome
timeFrame: Through duration of hospitalization, up to 12 weeks following admission
Secondary outcomes:
measure: All-cause in-hospital mortality
timeFrame: Through duration of hospitalization, up to 12 weeks following admission
measure: Renal failure requiring new initiation of renal replacement therapy
timeFrame: Through duration of hospitalization, up to 12 weeks following admission
measure: Need for cardiac transplant or mechanical circulatory support
timeFrame: Through duration of hospitalization, up to 12 weeks following admission
measure: Atrial or ventricular arrhythmia leading to emergent electrical cardioversion
timeFrame: Through duration of hospitalization, up to 12 weeks following admission
measure: Resuscitated cardiac arrest
timeFrame: Through duration of hospitalization, up to 12 weeks following admission
measure: Non-fatal myocardial infarction
timeFrame: Through duration of hospitalization, up to 12 weeks following admission
measure: Stroke or transient ischemic attack
timeFrame: Through duration of hospitalization, up to 12 weeks following admission
Other outcomes:
measure: Need for non-invasive or invasive mechanical ventilation
timeFrame: Through duration of hospitalization, up to 12 weeks following admission
measure: Arrhythmia requiring pharmacologic intervention
timeFrame: Through duration of hospitalization, up to 12 weeks following admission
measure: Acute kidney injury
timeFrame: Through duration of hospitalization, up to 12 weeks following admission
Locations:
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Hamilton
country: Canada
facility: Hamilton Health Sciences
state: Ontario
city: Ottawa
country: Canada
facility: University of Ottawa Heart Institute
state: Ontario
Study officials:
affiliation: Ottawa Heart Institute Research Corporation
name: Rebecca Mathew, MD
role: PRINCIPAL_INVESTIGATOR
References: