What is the mechanism of action of this treatment?

Cardiogenic shock treatments like Milrinone and Dobutamine work by increasing the heart's contractility to improve cardiac output. Milrinone inhibits phosphodiesterase-3 (PDE3), raising cyclic AMP (cAMP) levels and enhancing calcium influx into heart cells, which improves contractility and causes vasodilation. Dobutamine is a beta-1 adrenergic agonist that stimulates beta-1 receptors in the heart, increasing cAMP and calcium levels, thereby boosting heart muscle contractility. These mechanisms are vital for cardiogenic shock patients as they help restore adequate blood flow and oxygen delivery to vital organs, improving survival and reducing complications.

What side effects are associated with this type of intervention?

Milrinone and Dobutamine, commonly used inotropes for treating cardiogenic shock, have several known side effects. Milrinone can cause arrhythmias, hypotension, and thrombocytopenia. Dobutamine may also lead to arrhythmias and can cause tachycardia and increased myocardial oxygen consumption, potentially exacerbating ischemia. Both medications require careful monitoring to manage these risks effectively.

What prior FDA approvals exist?

Milrinone and Dobutamine are inotropes commonly used to manage cardiogenic shock by enhancing cardiac contractility and output. Milrinone, a phosphodiesterase-3 inhibitor, and Dobutamine, a beta-1 adrenergic agonist, have both been studied extensively and are widely used in clinical practice. These drugs are often chosen based on their specific pharmacological profiles and the clinical status of the patient. While the FDA has approved these agents for use in heart failure and other conditions requiring inotropic support, their use in cardiogenic shock is based on clinical guidelines and physician discretion.

What other types of research exist?

One promising alternative to Milrinone or Dobutamine for cardiogenic shock is Levosimendan. Levosimendan is a calcium sensitizer and potassium channel opener that enhances myocardial contractility without significantly increasing myocardial oxygen demand. It has shown benefits in improving hemodynamics and outcomes in patients with acute heart failure and cardiogenic shock. Another potential alternative is Omecamtiv Mecarbil, a cardiac myosin activator that increases the duration of cardiac muscle contraction, thereby improving cardiac output. Both agents are being studied for their efficacy and safety in critically ill patients.

← Back to Search

Inotrope

Inotrope Therapy for Cardiogenic Shock (DOREMI-2 Trial)

Phase 4

Recruiting

Led By Rebecca Mathew, MD

Research Sponsored by Ottawa Heart Institute Research Corporation

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

SCAI class C or D cardiogenic shock

Adult patients ≥ 18 years of age admitted to an intensive care unit

Must not have

Severe obstructive valvular lesions, including aortic stenosis and/or mitral stenosis

Patients presenting with an out-of-hospital cardiac arrest (OHCA)

Timeline

Screening 3 weeks

Treatment Varies

Follow Up through duration of hospitalization, up to 12 weeks following admission

Awards & highlights

All Individual Drugs Already Approved

Approved for 5 Other Conditions

Drug Has Already Been Approved

Pivotal Trial

Summary

This trial is testing whether drugs that help the heart pump better are beneficial for very sick patients with severe heart problems. These patients are in intensive care because their hearts can't pump enough blood. The study will compare two common drugs, Milrinone and Dobutamine, to see if they improve patient outcomes.

Who is the study for?

This trial is for adults over 18 in intensive care with a severe form of heart failure called cardiogenic shock. It's not for pregnant or breastfeeding individuals, those who can't consent, had an out-of-hospital cardiac arrest, took certain heart medications recently, or have specific severe heart valve problems.

What is being tested?

The study tests if drugs that boost the heart's pumping ability (inotropes) help critically ill patients. Participants will randomly receive either Milrinone, Dobutamine, or a placebo without knowing which one. After 12 hours they may continue treatment based on their doctor’s decision.

What are the potential side effects?

Possible side effects from Milrinone and Dobutamine include irregular heartbeat, blood pressure changes, headaches, nausea and potential worsening of the condition being treated. The exact side effects will vary between individuals.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

Select...

I have severe heart failure.

Select...

I am 18 or older and currently in intensive care.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

I have a severe blockage in my heart valves.

Select...

I had a cardiac arrest outside of a hospital.

Select...

My heart has a specific type of blockage affecting its pumping.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ through duration of hospitalization, up to 12 weeks following admission

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~through duration of hospitalization, up to 12 weeks following admission

This trial's timeline: 3 weeks for screening, Varies for treatment, and through duration of hospitalization, up to 12 weeks following admission for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Primary composite outcome

Secondary study objectives

All-cause in-hospital mortality

Atrial or ventricular arrhythmia leading to emergent electrical cardioversion

Need for cardiac transplant or mechanical circulatory support

+4 more

Other study objectives

Acute kidney injury

Arrhythmia requiring pharmacologic intervention

Need for non-invasive or invasive mechanical ventilation

Awards & Highlights

All Individual Drugs Already Approved

Therapies where all constituent drugs have already been approved are likely to have better-understood side effect profiles.

Approved for 5 Other Conditions

This treatment demonstrated efficacy for 5 other conditions.

Drug Has Already Been Approved

The FDA has already approved this drug, and is just seeking more data.

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

2Treatment groups

Active Control

Placebo Group

Group I: InotropeActive Control2 Interventions

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.

Group II: PlaceboPlacebo Group1 Intervention

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.

0 / 5Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Cardiogenic shock treatments like Milrinone and Dobutamine work by increasing the heart's contractility to improve cardiac output. Milrinone inhibits phosphodiesterase-3 (PDE3), raising cyclic AMP (cAMP) levels and enhancing calcium influx into heart cells, which improves contractility and causes vasodilation. Dobutamine is a beta-1 adrenergic agonist that stimulates beta-1 receptors in the heart, increasing cAMP and calcium levels, thereby boosting heart muscle contractility. These mechanisms are vital for cardiogenic shock patients as they help restore adequate blood flow and oxygen delivery to vital organs, improving survival and reducing complications.