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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial compares two treatments, Milrinone (Primacor) and Dobutamine (Dobutrex), for patients with cardiogenic shock, a condition where the heart suddenly can't pump enough blood. Researchers aim to determine if differences in heart muscle recovery can predict long-term patient outcomes. Eligible participants should have a heart failure diagnosis with reduced heart pumping ability (less than 40% effectiveness) and be undergoing tests or evaluations for advanced heart treatments due to worsening conditions. As an Early Phase 1 trial, this research focuses on understanding how these treatments work in people, offering participants a chance to contribute to groundbreaking insights.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that both milrinone and dobutamine are generally safe treatments for cardiogenic shock, a severe type of heart failure. Studies have found no major differences in the safety of these two drugs for patients with this condition. As inotropes, milrinone and dobutamine help the heart pump more effectively.

Data indicates that milrinone does not increase the risk of death compared to dobutamine. Some studies even suggest that milrinone might lower the risk of death in certain situations. While both treatments are used in medical settings, they can cause side effects like changes in blood pressure or heart rhythm. Healthcare professionals typically monitor and manage these side effects.

Overall, previous studies suggest that both milrinone and dobutamine are safe options for treating cardiogenic shock. Participants in clinical trials can expect close monitoring to ensure their safety while receiving these treatments. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Milrinone and Dobutamine for treating cardiogenic shock because they offer unique approaches to support heart function. Milrinone is known for its vasodilating properties, which can improve cardiac output by easing the heart's workload and enhancing blood flow. This is different from Dobutamine, which primarily increases the heart's pumping strength. By comparing these two, researchers aim to determine which is more effective in rapidly stabilizing patients, potentially leading to quicker recovery times.

What evidence suggests that this trial's treatments could be effective for cardiogenic shock?

This trial will compare Milrinone and Dobutamine for treating cardiogenic shock. Previous studies have evaluated these treatments for effectiveness in this condition, where the heart can't pump enough blood to meet the body's needs. Some research suggests Milrinone might slightly outperform Dobutamine in reducing the risk of death from any cause, with one study indicating a preference in observational studies (odds ratio 1.19). However, other studies found no major difference between the two treatments regarding main outcomes. Milrinone showed a lower risk of main outcomes and death in patients without certain complications, but not universally. Overall, while Milrinone may offer some benefits, its effectiveness compared to Dobutamine varies across studies. Participants in this trial will receive either Milrinone or Dobutamine to further evaluate their comparative effectiveness. ^{1 2 3 4 6}

Who Is on the Research Team?

Valluvan Jeevanandam, MD

Principal Investigator

University of Chicago

Are You a Good Fit for This Trial?

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

History of significant ventricular arrhythmia without an ICD

My kidney function is severely reduced.

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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 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]

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 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 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 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]

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa2026845

Milrinone as Compared with Dobutamine in the Treatment ... In patients with cardiogenic shock, no significant difference between milrinone and dobutamine was found with respect to the primary composite ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10465094/

Efficacy of Milrinone and Dobutamine in Cardiogenic Shock The primary outcome, all-cause mortality, favored milrinone in observational studies only (odds ratio [OR] 1.19 (95% CI, 1.02–1.39; p = 0.02).

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37649849/

Efficacy of Milrinone and Dobutamine in Cardiogenic Shock The primary outcome, all-cause mortality, favored milrinone in observational studies only (odds ratio [OR] 1.19 (95% CI, 1.02-1.39; p = 0.02).

4. sciencedirect.com sciencedirect.com/science/article/pii/S2049080122015230

Inotropic support in cardiogenic shock: who leads the battle ... Primary outcomes occurred more frequently in the Dobutamine group compared to Milrinone (54% vs 49%; RR 0.90; 95% CI, 0.69–1.19, p = 0.47). However, these were ...

5. jacc.org jacc.org/doi/10.1016/j.jacadv.2023.100393

Milrinone vs Dobutamine for the Management of ... The interaction was characterized by lower risk of primary outcome and death with milrinone compared to dobutamine in patients without, but not ...

6. journals.lww.com journals.lww.com/ccejournal/fulltext/2023/09000/efficacy_of_milrinone_and_dobutamine_in.10.aspx

Efficacy of Milrinone and Dobutamine in Cardiogenic ... Based on the current data available, there is a consistent trend toward a reduction in in-hospital mortality with milrinone use in CS when compared with ...