CAPITAL DOREMI 2: Inotrope Versus Placebo Therapy for Cardiogenic Shock

NCT05267886 | Recruiting Phase 4 DMC

• 1 other identifier: 20210386
• Study Type: interventional
• Target: 346
• Locations: 2 countries
• Sites: 3

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.

Conditions

Shock, Cardiogenic

Keywords

cardiogenic; shock; inotrope

Outcome Measures

Primary Outcomes (1)

• Primary composite outcome

  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

  Through duration of hospitalization, up to 12 weeks following admission

Secondary Outcomes (7)

• All-cause in-hospital mortality

  Through duration of hospitalization, up to 12 weeks following admission

• Renal failure 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

  Through duration of hospitalization, up to 12 weeks following admission

• Atrial or ventricular arrhythmia leading to emergent electrical cardioversion

  Through duration of hospitalization, up to 12 weeks following admission

• Resuscitated cardiac arrest

  Through duration of hospitalization, up to 12 weeks following admission

Other Outcomes (3)

• Need for non-invasive or invasive mechanical ventilation

  Through duration of hospitalization, up to 12 weeks following admission

• Arrhythmia requiring pharmacologic intervention

  Through duration of hospitalization, up to 12 weeks following admission

• Acute kidney injury

  Through duration of hospitalization, up to 12 weeks following admission

Study Arms (2)

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.

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.

Drug: Normal Saline

Interventions

Dobutamine DRUG

Dobutamine administered according to its clinical dose stage for cardiogenic shock

Also known as: Dobutrex, Inotrex

Inotrope

Milrinone DRUG

Milrinone administered according to its clinical dose stage for cardiogenic shock

Inotrope

Normal Saline DRUG

Normal saline running at a standardized rate

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Ottawa Heart Institute Research Corporation: lead

Study Sites (3)

Mayo Clinic

Rochester, Minnesota, 55905, United States

NOT YET RECRUITING

Hamilton Health Sciences

Hamilton, Ontario, L8L 2X2, Canada

RECRUITING

University of Ottawa Heart Institute

Ottawa, Ontario, K1Y4W7, Canada

RECRUITING

MeSH Terms

Conditions

Shock, Cardiogenic; Shock

Interventions

Dobutamine; Milrinone; Saline Solution

Condition Hierarchy (Ancestors)

Myocardial Infarction; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis

Intervention Hierarchy (Ancestors)

Catecholamines; Amines; Organic Chemicals; Phenethylamines; Ethylamines; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Amrinone; Aminopyridines; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Rebecca Mathew, MD

  Ottawa Heart Institute Research Corporation

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rebecca Mathew, MD

CONTACT

613-696-7406; rmathew@ottawaheart.ca

Baylie Morgan, RN

CONTACT

613-696-7000; bmorgan@ottawaheart.ca

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Double-blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Parallel randomized control trial

Study Record Dates

• First Submitted: February 3, 2022
• First Posted: March 4, 2022
• Study Start: March 5, 2022
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: May 1, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Study completion
• Access Criteria: The above will be made publicly available

Locations

US (1); CA (2)