Milrinone vs Dobutamine for Cardiogenic Shock

Recruiting in Palo Alto (17 mi)

Overseen by Valluvan Jeevanandam, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase < 1

Recruiting

Sponsor: University of Chicago

Disqualifiers: Severe coronary artery disease, others

No Placebo Group

Trial Summary

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.

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}

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.

Trial 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 (Beta-1 Adrenergic Receptor Agonist)
• Milrinone (Phosphodiesterase Inhibitor)

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 Dobutamine or Milrinone Active Control 1 Intervention

Patients will be randomized 1:1 to either Milrinone or Dobutamine. Dobutamine will be infused at 10-40 mcg/kg/min during the infusion phase, and for those randomized to dobutamine for maintenance, they will be kept at 5-10 mcg/kg/min. Milrinone will be given as a bolus at a dose of 5 mcg/kg/min over 15 minutes, for a total of 75 mcg/kg. For patients randomized to the arm for maintenance milrinone, they will be maintained at 0.125-0.375 mcg/kg/min.

Group II: 1:1 Randomization to Milrinone or Dobutamine Active Control 1 Intervention

Patients will be randomized 1:1 to either Milrinone or Dobutamine. Milrinone will be given as a bolus at a dose of 5 mcg/kg/min over 15 minutes, for a total of 75 mcg/kg. For patients randomized to the arm for maintenance milrinone, they will be maintained at 0.125-0.375 mcg/kg/min. Patients may be randomized to dobutamine will be infused at 10-40 mcg/kg/min during the infusion phase and for those randomized to dobutamine for maintenance, they will be kept at 5-10 mcg/kg/min.

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

The University of Chicago Chicago, IL

Who Is Running the Clinical Trial?

University of Chicago Lead Sponsor

References

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

Improved mortality and haemodynamics with milrinone in cardiogenic shock due to acute decompensated heart failure. [2023] Studies in cardiogenic shock (CS) often have a heterogeneous population of patients, including those with acute myocardial infarction and acute decompensated heart failure (ADHF-CS). The therapeutic profile of milrinone may benefit patients with ADHF-CS. We compared the outcomes and haemodynamic trends in ADHF-CS receiving either milrinone or dobutamine.

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

Efficacy of Milrinone and Dobutamine in Cardiogenic Shock: An Updated Systematic Review and Meta-Analysis. [2023] Inotropic support is commonly used in patients with cardiogenic shock (CS). High-quality data guiding the use of dobutamine or milrinone among this patient population is limited. We compared the efficacy and safety of these two inotropes among patients with low cardiac output states (LCOS) or CS.

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

Comparative Effectiveness and Safety Between Milrinone or Dobutamine as Initial Inotrope Therapy in Cardiogenic Shock. [2020] Inotropes are an integral component of the early stabilization of the patient presenting with cardiogenic shock. Despite years of clinical experience with the 2 most commonly used inotropes, dobutamine and milrinone, there remains limited data comparing outcomes between the two. We conducted a retrospective review to compare the effectiveness and safety of milrinone or dobutamine for the initial management of cardiogenic shock. Adult patients with cardiogenic shock regardless of etiology who received initial inotrope therapy with either milrinone (n = 50) or dobutamine (n = 50) and did not receive mechanical circulatory support were included. The primary end point was the time to resolution of cardiogenic shock. Changes in hemodynamic parameters from baseline and adverse events were also assessed. Resolution of shock was achieved in similar numbers in both the groups (milrinone 76% vs dobutamine 70%, P = .50). The median time to resolution of shock was 24 hours in both groups (P = .75). There were no differences in hemodynamic changes during inotrope therapy, although dobutamine trended toward a greater increase in cardiac index. Arrhythmias were more common in patients treated with dobutamine than milrinone, respectively (62.9% vs 32.8%, P &lt; .01), whereas hypotension occurred to a similar extent in both groups (milrinone 49.2% vs dobutamine 40.3%, P = .32). The use of concomitant vasoactive medications, dosage required, and duration of therapy did not differ between groups. There was no difference in the overall rate of discontinuation due to adverse event; however, milrinone was more commonly discontinued due to hypotension (13.1% vs 0%, P &lt; .01) and dobutamine was more commonly discontinued due to arrhythmia (0% vs 11.3%, P &lt; .01). Milrinone and dobutamine demonstrated similar effectiveness and safety profiles but with differences in adverse events. The choice of milrinone or dobutamine as initial inotrope therapy for cardiogenic shock may depend more on tolerability of adverse events.

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

Significant Valvular Dysfunction and Outcomes in Cardiogenic Shock: Insights From the Randomized DOREMI Trial. [2022] Patients with cardiogenic shock (CS) suffer high rates of in-hospital mortality, with little evidence guiding management. The impact of valvular heart disease in patients with CS remains unclear. We therefore conducted a post hoc analysis of the randomized Dobutamine Compared to Milrinone (DOREMI) trial to determine the impact of valvular disease on outcomes in patients with CS.

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] Milrinone and dobutamine are positive inotropic agents with beneficial hemodynamic effects in patients with congestive heart failure. This study was undertaken to compare the effects of intravenous milrinone and dobutamine in patients with stable New York Heart Association class III or IV congestive heart failure and to test the hypothesis that intravenous milrinone is at least as beneficial as dobutamine in this setting. Seventy-nine patients were randomized to either dobutamine therapy at incremental doses of 2.5, 5, 7.5, 10, 12.5 and 15 micrograms/kg/min, or milrinone as a bolus of 50 or 75 micrograms/kg followed by an infusion of 0.5 to 1.0 micrograms/kg/min. Both agents significantly increased heart rate, cardiac index and stroke volume index and decreased pulmonary artery wedge pressure and systemic vascular resistance compared with baseline levels (p less than 0.01). During sustained infusion for 48 hours, no difference in hemodynamic effects was observed between the 2 drugs. Ventricular tachycardia occurred in 5 patients (3 taking milrinone, 2 taking dobutamine); 1 patient taking milrinone had ventricular fibrillation. Milrinone and dobutamine elicited similar beneficial hemodynamic results with relatively few adverse effects.

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

Efficacy of milrinone and dobutamine in low cardiac output states: Systematic review and meta-analysis. [2021] Patients in cardiac intensive care units (ICU) are admitted with increasingly higher disease acuity and a larger burden of non-cardiac critical illness. Accordingly, positive inotropes are being used with increased frequency and little comparative data to support drug selection. We compared the effectiveness and safety of dobutamine and milrinone in low cardiac output states (LCOS) and/or cardiogenic shock (CS).

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

Implications of Myocardial Infarction on Management and Outcome in Cardiogenic Shock. [2022] Background The randomized DOREMI (Dobutamine Compared to Milrinone) clinical trial evaluated the efficacy and safety of milrinone and dobutamine in patients with cardiogenic shock. Whether the results remain consistent when stratified by acute myocardial infarction remains unknown. In this substudy, we sought to evaluate differences in clinical management and outcomes of acute myocardial infarction complicated by cardiogenic shock (AMICS) versus non-AMICS. Methods and Results Patients in cardiogenic shock (n=192) were randomized 1:1 to dobutamine or milrinone. The primary composite end point in this subgroup analysis was all-cause in-hospital mortality, cardiac arrest, non-fatal myocardial infarction, cerebrovascular accident, the need for mechanical circulatory support, or initiation of renal replacement therapy (RRT) at 30-days. Outcomes were evaluated in patients with (n=65) and without (n=127) AMICS. The primary composite end point was significantly higher in AMICS versus non-AMICS (hazard ratio [HR], 2.21; 95% CI, 1.47-3.30; P=0.0001). The primary end point was driven by increased rates of all-cause mortality, mechanical circulatory support, and RRT. No differences in other secondary outcomes including cardiac arrest or cerebrovascular accident were observed. AMICS remained associated with the primary composite outcome, 30-day mortality, and RRT after adjustment for age, sex, procedural contrast use, multivessel disease, and inotrope type. Conclusions AMI was associated with increased rates of adverse clinical outcomes in cardiogenic shock along with increased rates of mortality and initiation of mechanical circulatory support and RRT. Contrast administration during revascularization likely contributes to increased rates of RRT. Heterogeneity of outcomes in AMICS versus non-AMICS highlights the need to study interventions in specific subgroups of cardiogenic shock. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03207165.

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

Inotropic support in cardiogenic shock: who leads the battle, milrinone or dobutamine? [2022] Cardiovascular diseases remain the leading cause of death globally, with acute myocardial infarction being one of the most frequent. One of the complications that can occur after a myocardial infarction is cardiogenic shock. At present, the evidence on the use of inotropic agents for the management of this complication is scarce, and only a few trials have evaluated the efficacy-adverse effects relationship of some agents. Milrinone and Dobutamine are some of the most frequently mentioned drugs that have been studied recently. However, there are still no data that affirm with certainty the supremacy of one over the other. The aim of this review is to synthesize evidence on basic and practical aspects of these agents, allowing us to conclude which might be more useful in current clinical practice, based on the emerging literature.