Inotrope Therapy for Cardiogenic Shock

(DOREMI-2 Trial)

Recruiting at 2 trial locations

Overseen By Baylie Morgan, RN

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Ottawa Heart Institute Research Corporation

Must be taking: Inotropes

Must not be taking: Milrinone, Dobutamine

Disqualifiers: Pregnancy, Breast-feeding, OHCA, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 12 hours

346 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

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 Dobutamine and Milrinone for treating cardiogenic shock?

Research shows that both Dobutamine and Milrinone are effective in resolving cardiogenic shock, with similar success rates and time to resolution. However, they have different side effects, with Dobutamine more likely to cause irregular heartbeats and Milrinone more likely to cause low blood pressure. ^{1 2 3 4 5}

Is inotrope therapy with milrinone or dobutamine safe for humans?

Milrinone and dobutamine are generally safe for humans, but they can have different side effects. Milrinone may cause low blood pressure, while dobutamine may lead to irregular heartbeats. Both drugs have been used safely in patients with heart conditions, but the choice between them often depends on which side effects are more tolerable for the patient. ^{1 2 3 5 6}

How do the drugs dobutamine and milrinone differ from other treatments for cardiogenic shock?

Dobutamine and milrinone are unique in their ability to improve heart function by increasing the strength of heart contractions, which can help stabilize patients with cardiogenic shock. Unlike some other treatments, they are administered intravenously (through a vein) and are often chosen based on their different side effect profiles, with dobutamine more likely to cause arrhythmias (irregular heartbeats) and milrinone more likely to cause hypotension (low blood pressure). ^{1 3 4 5 6}

Research Team

Rebecca Mathew, MD

Principal Investigator

Ottawa Heart Institute Research Corporation

Eligibility Criteria

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.

Inclusion Criteria

I have severe heart failure.

I am 18 or older and currently in intensive care.

Exclusion Criteria

Patients who are currently pregnant or breast-feeding

Unwilling or unable to obtain informed consent by the participant or substitute decision maker

I have been given milrinone or dobutamine in the last 24 hours.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive inotrope or placebo therapy for cardiogenic shock, with doses adjusted based on clinical status

12 hours

Continuous monitoring in CICU

Open-label Treatment

Participants move to open-label treatment where continued use of inotropes is at the discretion of the treating physician

Duration of hospitalization

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 12 weeks following admission

Treatment Details

Interventions

• Dobutamine
• Milrinone
• Normal Saline

Trial Overview 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.

Participant Groups

Group I: Inotrope Active Control 2 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: Placebo Placebo Group 1 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.

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?

Ottawa Heart Institute Research Corporation

Lead Sponsor

Trials

200

Recruited

95,800+

Findings from Research

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 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 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]

Inotropes and inopressors, such as dobutamine and norepinephrine, are critical first-line treatments for patients experiencing cardiogenic shock, helping to improve heart function and blood pressure.

The article reviews the pharmacology and clinical use of these medications, highlighting their indications and contraindications in managing acute decompensated heart failure and cardiogenic shock.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Review of Inotropes and Inopressors for Effective Utilization in Patients With Acute Decompensated Heart Failure. Nandkeolyar, S., Ryu, R., Mohammad, A., 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 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]

References

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

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

2. Canada pubmed.ncbi.nlm.nih.gov

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

3. England pubmed.ncbi.nlm.nih.gov

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

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

A Review of Inotropes and Inopressors for Effective Utilization in Patients With Acute Decompensated Heart Failure. [2023]

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

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

6. 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]