Milrinone vs Dobutamine for Cardiogenic Shock

Overseen By Daniel Rodgers

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of Chicago

Disqualifiers: Severe coronary artery disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

5 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drugs Milrinone and Dobutamine for treating cardiogenic shock?

Both Milrinone and Dobutamine are shown to be effective in resolving cardiogenic shock, with similar rates of success and time to resolution. However, they differ in side effects, with Milrinone more likely to cause low blood pressure and Dobutamine more likely to cause irregular heartbeats. ^{1 2 3 4 5}

Is Milrinone or Dobutamine safe for treating cardiogenic shock?

Both Milrinone and Dobutamine are generally safe for treating cardiogenic shock, but they have different side effects. Milrinone may cause low blood pressure, while Dobutamine may lead to irregular heartbeats. ^{1 2 3 6 7}

How do the drugs milrinone and dobutamine differ in treating cardiogenic shock?

Milrinone and dobutamine are both drugs used to help the heart pump better in cardiogenic shock, but they have different side effects. Milrinone is less likely to cause irregular heartbeats (arrhythmias) but may lead to low blood pressure, while dobutamine is more likely to cause arrhythmias. ^{1 2 3 5 8}

What is the purpose of this trial?

The main purpose of this study is to determine whether differences in myocardial reserve predict clinical outcomes for heart failure patients.

Research Team

Valluvan Jeevanandam, MD

Principal Investigator

University of Chicago

Eligibility Criteria

This trial is for adults over 18 with severe heart failure (LVEF ≤ 35%) who are being evaluated for advanced treatments like LVAD, heart transplants, or other therapies. They must have a kidney function above a certain level (eGFR ≥ 30 ml/min/1.73 m2) and be hospitalized based on specific heart health measurements.

Inclusion Criteria

Intent for admission based on RHC data

My heart's pumping ability is significantly reduced.

I am being evaluated for heart function recovery to possibly remove or adjust my heart support device.

Exclusion Criteria

My kidney function is severely reduced.

History of significant ventricular arrhythmia without an ICD

I have severe heart artery blockage that hasn't been treated with surgery.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients are randomized to receive either Milrinone or Dobutamine to assess myocardial reserve and clinical outcomes

12 weeks

Multiple visits during hospitalization

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Treatment Details

Interventions

• Dobutamine
• Milrinone

Trial Overview The study aims to see if milrinone or dobutamine better improves cardiac power output in patients with cardiogenic shock. Patients will be randomly assigned to receive either drug in equal numbers to compare their effects on the heart's pumping ability.

Participant Groups

Group I: 1:1 Randomization to Milrinone Active Control 1 Intervention

Milrinone will be given as a bolus dose of 50 mcg/kg. If a maintenance milrinone infusion is felt to be necessary, it will be maintained at 0.125-0.375 mcg/kg/min.

Group II: 1:1 No Intervention Active Control 1 Intervention

Subjects without evidence of cardiogenic shock will not receive Milrinone.

Dobutamine is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Dobutrex for:

• Cardiogenic shock
• Heart failure

Approved in European Union as Dobutamine for:

• Cardiogenic shock
• Acute heart failure

Approved in Canada as Dobutamine for:

• Cardiogenic shock
• Heart failure

Who Is Running the Clinical Trial?

University of Chicago

Lead Sponsor

Trials

1,086

Recruited

844,000+

Findings from Research

In a study of 573 patients with acute decompensated heart failure and cardiogenic shock, milrinone was associated with a significantly lower risk of 30-day mortality compared to dobutamine, with a hazard ratio of 0.52, indicating a 48% reduction in risk.

Patients receiving milrinone also showed improved hemodynamic parameters, such as better pulmonary artery compliance and stroke volume, suggesting that milrinone may be more effective in managing this condition than dobutamine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improved mortality and haemodynamics with milrinone in cardiogenic shock due to acute decompensated heart failure. Rodenas-Alesina, E., Luis Scolari, F., Wang, VN., et al.[2023]

In a meta-analysis of 11 studies involving 21,084 patients with low cardiac output states or cardiogenic shock, milrinone showed a potential benefit in reducing all-cause mortality compared to dobutamine, although this was only evident in observational studies.

Dobutamine was associated with a shorter length of hospital stay, suggesting it may be more effective for quicker recovery, but it also raised concerns about a potential increase in mortality, highlighting the need for larger randomized trials to clarify these outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Milrinone and Dobutamine in Cardiogenic Shock: An Updated Systematic Review and Meta-Analysis. Abdel-Razek, O., Di Santo, P., Jung, RG., et al.[2023]

In a study of 100 adult patients with cardiogenic shock, both milrinone and dobutamine were found to be similarly effective in resolving shock, with resolution rates of 76% and 70% respectively, and a median time to resolution of 24 hours for both groups.

While both inotropes had comparable overall safety profiles, dobutamine was associated with a higher incidence of arrhythmias (62.9% vs 32.8% for milrinone), suggesting that the choice between the two may depend on the patient's tolerance for specific side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative Effectiveness and Safety Between Milrinone or Dobutamine as Initial Inotrope Therapy in Cardiogenic Shock. Lewis, TC., Aberle, C., Altshuler, D., et al.[2020]

In a study of 189 patients with cardiogenic shock, those with significant valvular disease had a higher in-hospital mortality rate (48.7%) compared to those without (32.2%), indicating that valvular dysfunction worsens outcomes in this condition.

Specific types of valvular disease, such as aortic stenosis and mitral regurgitation, were linked to even greater risks of in-hospital death, highlighting the need for targeted interventions in patients with these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Significant Valvular Dysfunction and Outcomes in Cardiogenic Shock: Insights From the Randomized DOREMI Trial. Parlow, S., Weng, W., Di Santo, P., et al.[2022]

In a study of 79 patients with stable congestive heart failure, both milrinone and dobutamine significantly improved heart function without major differences in their hemodynamic effects over 48 hours.

Both medications were associated with a low incidence of adverse effects, although there were some cases of ventricular tachycardia and one case of ventricular fibrillation in the milrinone group, indicating that while both drugs are effective, careful monitoring is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of intravenous milrinone and dobutamine for congestive heart failure secondary to either ischemic or dilated cardiomyopathy. Biddle, TL., Benotti, JR., Creager, MA., et al.[2019]

In a systematic review of 11 studies involving 23,056 patients, dobutamine was associated with a shorter length of stay in the ICU compared to milrinone, suggesting it may be more effective in managing low cardiac output states and cardiogenic shock.

While milrinone trended towards lower all-cause mortality, the difference was not statistically significant, indicating a potential risk that requires further investigation through randomized trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of milrinone and dobutamine in low cardiac output states: Systematic review and meta-analysis. Mathew, R., Visintini, SM., Ramirez, FD., et al.[2021]

In the DOREMI trial involving 192 patients with cardiogenic shock, those with acute myocardial infarction complicated by cardiogenic shock (AMICS) experienced significantly worse outcomes, including higher rates of in-hospital mortality and the need for mechanical circulatory support compared to those without AMICS.

The study found that AMICS was associated with a 2.21 times higher risk of adverse outcomes, emphasizing the importance of tailored interventions for patients with AMICS in future clinical research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Implications of Myocardial Infarction on Management and Outcome in Cardiogenic Shock. Jung, RG., Di Santo, P., Mathew, R., et al.[2022]

Cardiovascular diseases, particularly acute myocardial infarction, are a leading cause of death worldwide, and complications like cardiogenic shock require effective management strategies.

Current evidence on inotropic agents like Milrinone and Dobutamine for treating cardiogenic shock is limited, with no definitive conclusions on which agent is superior, highlighting the need for further research in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inotropic support in cardiogenic shock: who leads the battle, milrinone or dobutamine? Lozada Martinez, ID., Bayona-Gamboa, AJ., Meza-Fandiño, DF., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Improved mortality and haemodynamics with milrinone in cardiogenic shock due to acute decompensated heart failure. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Efficacy of Milrinone and Dobutamine in Cardiogenic Shock: An Updated Systematic Review and Meta-Analysis. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Comparative Effectiveness and Safety Between Milrinone or Dobutamine as Initial Inotrope Therapy in Cardiogenic Shock. [2020]

4. England pubmed.ncbi.nlm.nih.gov

Significant Valvular Dysfunction and Outcomes in Cardiogenic Shock: Insights From the Randomized DOREMI Trial. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Comparison of intravenous milrinone and dobutamine for congestive heart failure secondary to either ischemic or dilated cardiomyopathy. [2019]

6. Canada pubmed.ncbi.nlm.nih.gov

Efficacy of milrinone and dobutamine in low cardiac output states: Systematic review and meta-analysis. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Implications of Myocardial Infarction on Management and Outcome in Cardiogenic Shock. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Inotropic support in cardiogenic shock: who leads the battle, milrinone or dobutamine? [2022]