Milrinone for Heart Function After Surgery

(MIDAS Trial)

Recruiting at 18 trial locations

Overseen By Patrick J McNamara

Age: < 18

Sex: Any

Trial Phase: Phase 3

Sponsor: NICHD Neonatal Research Network

Must not be taking: Vasodilators, Inodilators

Disqualifiers: Congenital malformation, Heart disease, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 3-5 days

316 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether milrinone (also known as Primacor) can improve heart function in infants after surgery to close a patent ductus arteriosus (PDA), a heart condition. Researchers aim to determine if milrinone reduces the risk of death or severe lung problems within a week of surgery and enhances survival and brain development over two years. The trial includes a milrinone group and a placebo group for comparison. Suitable candidates for this trial are infants born very early (before 28 weeks), under three months old, requiring breathing support, and scheduled for PDA closure surgery. As a Phase 3 trial, this study represents the final step before FDA approval, offering a chance to contribute to potentially life-saving advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it excludes those who are currently using vasodilator or inodilator agents. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that milrinone is likely to be safe for humans?

Research has shown that milrinone aids the heart in pumping blood more effectively during heart surgeries. It can reduce the risk of low cardiac output syndrome, particularly at higher doses. However, some studies found that milrinone might increase the risk of irregular heartbeats and potentially higher mortality rates in adults after heart surgery. While milrinone offers benefits, it also carries risks. Prospective trial participants should discuss these findings with their doctor to understand their implications. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Milrinone is unique because it directly enhances heart muscle contraction and promotes blood vessel dilation, which can improve heart function after surgery. Unlike standard treatments that primarily stabilize heart rate and rhythm, milrinone works by increasing the heart's pumping strength and easing blood flow, potentially offering a quicker recovery for patients. Researchers are excited about milrinone because its dual action on the heart and blood vessels could lead to better outcomes and faster stabilization after cardiac surgery compared to traditional therapies.

What evidence suggests that milrinone might be an effective treatment for heart function after surgery?

In this trial, participants will receive either milrinone or a placebo to assess its effects on heart function after surgery. Research has shown that milrinone may improve heart performance post-surgery. One study found that milrinone lowered the risk of low cardiac output syndrome, a condition where the heart doesn't pump enough blood, by 48%. Another study found that it reduced heart attacks after surgery, with only 4.7% of patients experiencing a heart attack compared to 18% who did not use milrinone. Milrinone also helps lower pressure in the lungs' blood vessels, improving blood flow. While it might not reduce death rates in all cases, these findings suggest that milrinone could aid heart function and recovery after surgery. ^{3 5 6 7 8}

Are You a Good Fit for This Trial?

This trial is for infants who have undergone PDA closure, a heart procedure. It's designed to see if milrinone can help their hearts supply oxygen better post-surgery. Infants with specific conditions like Postpericardiotomy syndrome, Klinefelter Syndrome, and Triple X Syndrome are included.

Inclusion Criteria

Hemodynamically significant PDA with minimum transductal diameter ≥1.0 mm within 2 days of intervention

My baby was born at or before 27 weeks and 6 days and is younger than 3 months.

I use a machine to help with my breathing, but not just a simple nose tube.

Exclusion Criteria

Any major congenital malformation

Acute renal failure defined by urine output < 0.5 mL/kg/hour OR rise of serum creatinine by 0.3 mg/dL within 48 hours OR rise of serum creatinine more than 40% above baseline serum creatinine within prior 72 hours

I do not have significant congenital heart disease, except for very small defects.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Infants receive either milrinone or placebo after PDA closure, with close monitoring and dose adjustments based on response

3-5 days

Continuous monitoring during hospital stay

Follow-up

Participants are monitored for safety and effectiveness after treatment, including a follow-up visit at 2 years of age to assess neurodevelopmental outcomes

22 to 26 months

1 visit (in-person) at 2 years of age

Post-treatment Monitoring

Monitoring for post-ligation cardiac syndrome or death within 7 days of PDA closure

7 days

What Are the Treatments Tested in This Trial?

Interventions

• Milrinone

Trial Overview The study compares the effects of milrinone infusion versus a placebo on infant heart function after PDA closure surgery. The main focus is whether milrinone reduces death or PLCS risk within 7 days and its impact on two-year survival and neurodevelopment.

How Is the Trial Designed?

Group I: Milrinone Active Control 1 Intervention

An intravenous (iv) infusion of milrinone will be administered at an initial dose of 0.33 mcg/kg/min and accompanied by an iv bolus of 10 mL/kg of 0.9% NaCl (administered over 60 minutes).

Group II: Placebo Placebo Group 1 Intervention

An iv infusion of placebo (0.9% saline) of equivalent volume will be administered. The infusion will be accompanied by an iv bolus of 10 mL/kg of 0.9% NaCl (administered over 60 minutes) to ensure blinding is maintained.

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

Approved in United States as Primacor for:

• Acute heart failure
• Cardiogenic shock

Approved in Canada as Milrinone for:

• Acute heart failure
• Cardiogenic shock

Approved in European Union as Milrinone for:

• Acute heart failure

Who Is Running the Clinical Trial?

NICHD Neonatal Research Network

Lead Sponsor

Trials

62

Recruited

209,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Citations

1. bmccardiovascdisord.biomedcentral.com bmccardiovascdisord.biomedcentral.com/articles/10.1186/s12872-020-01598-8

The effect of milrinone on mortality in adult patients who ... Based on the current results, compared with placebo, milrinone might be unable to decrease mortality in adult CABG surgical patients but can ...

2. jcvaonline.com jcvaonline.com/article/S1053-0770(18)30941-8/fulltext

Milrinone in Adult Cardiac Surgery: More Evidence Is ... The researchers discovered that IvMil was associated with significantly lower mean pulmonary artery pressures and systemic vascular resistance ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4699515/

Effect of milrinone on cardiac functions in patients ... In milrinone group, five out of 106 patients (4.7%) had myocardial infarction 24 hours after CABG versus 19 out of 106 patients (18%) who had it ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/105307709290097Q

Intravenous milrinone following cardiac surgery: I. effects of ... The hemodynamic and adverse effects of intravenous milrinone were studied in 99 adult patients (66 men) following elective myocardial revascularization, ...

5. ahajournals.org ahajournals.org/doi/10.1161/01.cir.0000051365.81920.28

Efficacy and Safety of Milrinone in Preventing Low Cardiac ... The use of high-dose milrinone reduced the risk of the LCOS through the final visit by 48% (P=0.049). Conclusions— The use of high-dose milrinone after ...

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S105307701200417X

Meta-analysis of Randomized Trials of Effect of Milrinone ... A recent meta-analysis suggested that it might increase mortality in patients undergoing cardiac surgery.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7346403/

The effect of milrinone on mortality in adult patients who ... In some studies on cardiac surgeries, a tendency for an increased mortality rate and incidence of arrhythmia has been found in milrinone groups compared with ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3941037/

Relation of Milrinone Following Surgery for Congenital Heart ... Data from adults undergoing cardiac surgery suggest an association between milrinone and increased risk for postoperative arrhythmias.