Norepinephrine vs Vasopressin for Heart Surgery Patients

Overseen By Roberta Johnson

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: The Cleveland Clinic

Must be taking: Vasopressors

Must not be taking: Inhalational vasodilators

Disqualifiers: Transplant, Ventricular assist, others

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

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

Compensation: Varies

Number of Visits: 1

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two treatments, norepinephrine (a medication used to increase blood pressure) and vasopressin (a hormone that also raises blood pressure), to determine which is more effective for patients undergoing heart surgery who experience low blood pressure (hypotension). Researchers aim to understand how these drugs affect lung blood flow during surgery. Suitable participants are those scheduled for heart surgery with a pulmonary artery catheter to monitor their heart and who require continuous medication to maintain blood pressure. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants an opportunity to contribute to potentially groundbreaking treatments.

Do I need to stop my current medications for the trial?

The trial information does not specify if 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 has shown that norepinephrine is often used in intensive care, particularly during heart surgery, to control blood pressure. Some studies have found that it can sometimes cause problems like cardiac arrest, but this usually occurs in very sick patients. Norepinephrine is widely used, and doctors are very familiar with it.

Vasopressin is another medication used during and after heart surgery to stabilize blood pressure. Studies have shown that it generally controls blood pressure well without causing major side effects. In some cases, it even resulted in fewer issues, such as less chest tube drainage after surgery.

Both treatments have been used in similar situations before, and while risks exist, they are generally considered safe. This trial will directly compare their safety and effectiveness. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using norepinephrine and vasopressin for heart surgery patients because they offer different ways to manage blood pressure during surgery. Unlike standard treatments that primarily target the heart, norepinephrine and vasopressin work directly on blood vessels to adjust blood flow and pressure, which could lead to more stable outcomes during cardiac procedures. Norepinephrine acts as a powerful vasoconstrictor, increasing blood pressure by narrowing blood vessels, while vasopressin not only constricts blood vessels but also helps retain water in the body, potentially providing a more balanced hemodynamic effect. These unique mechanisms could make them particularly effective for maintaining stable circulation during heart surgery.

What evidence suggests that this trial's treatments could be effective for heart surgery patients?

This trial will compare norepinephrine and vasopressin in heart surgery patients. Research has shown that norepinephrine, one of the treatments in this trial, is often used to control blood pressure during heart surgery. It helps prevent low blood pressure, which is crucial for patient stability. However, some evidence suggests it might decrease urine output in patients with heart issues.

Studies have shown that vasopressin, the other treatment option, effectively manages blood flow after heart surgery and may cause fewer heart rhythm problems compared to norepinephrine. It is noted to handle blood pressure issues better after surgery, although it doesn't necessarily improve overall survival rates. Both treatments offer specific benefits for managing patients undergoing heart surgery. ^{1 6 7 8 9}

Who Is on the Research Team?

Mariya Geube, MD

Principal Investigator

The Cleveland Clinic

Are You a Good Fit for This Trial?

This trial is for adults over 18 who are having elective heart surgery with a device called CPB and need a pulmonary artery catheter. They must have low blood pressure during surgery needing drugs to raise it. It's not for those getting transplants, certain implants, specific lung surgeries, or using inhaled lung medicines before the study starts.

Inclusion Criteria

I need medication through an IV to maintain my blood pressure.

I am scheduled for heart surgery that will use a heart-lung machine.

I am over 18 years old.

Exclusion Criteria

I am getting a heart pump implant that is not an intra-aortic balloon.

I am scheduled for or have had a surgery to remove blood clots from my lungs.

I am scheduled for surgery to repair an aneurysm in my chest and abdomen.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Intraoperative Treatment

Participants receive vasopressor support with either vasopressin or norepinephrine during cardiac surgery

During surgery

1 visit (in-person, during surgery)

Immediate Postoperative Monitoring

Monitoring of mPAP-to-MAP ratio and RV function using transesophageal echocardiography

20 minutes after chest closure

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Norepinephrine
• Vasopressin

Trial Overview The study looks at how two drugs, Norepinephrine (NE) and Vasopressin (VP), affect blood pressure in the lungs compared to overall blood pressure during heart surgery. It also checks how these drugs influence right ventricle function when patients need vasopressor support.

How Is the Trial Designed?

Group I: use of vasopressin Active Control 1 Intervention

Hemodynamic effect of vasopressin on the pulmonary circulation in cardiac surgery patients

Group II: use of norepinephrine Active Control 1 Intervention

Hemodynamic effect of norepinephrine on the pulmonary circulation in cardiac surgery patients

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

Approved in United States as Levophed for:

• Severe, acute hypotension
• Cardiac arrest

Approved in Canada as Norepinephrine Bitartrate for:

• Severe, acute hypotension
• Cardiac arrest

Approved in European Union as Noradrenaline for:

• Severe, acute hypotension
• Cardiac arrest

Who Is Running the Clinical Trial?

The Cleveland Clinic

Lead Sponsor

Trials

1,072

Recruited

1,377,000+

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S2352556823000085

Epidemiology, risk factors and outcomes of norepinephrine ... Of 9316 patients screened during the study period, 2862 were included and 2510 were analyzed. Among them, 1549 (61%) were treated with norepinephrine with a ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36758855/

Epidemiology, risk factors and outcomes of norepinephrine ... Epidemiology, risk factors and outcomes of norepinephrine use in cardiac surgery with cardiopulmonary bypass: a multicentric prospective study.

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40233952/

A Prospective double-blind, randomised controlled trial ... A Prospective double-blind, randomised controlled trial comparing angiotensin II to norepinephrine to reduce length of hospital stay in cardiac ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05335954

NCT05335954 | Therapeutic Study Evaluating the Efficacy ... Therapeutic Study Evaluating the Efficacy of Noradrenaline in the Prevention of Hypotension Related to Intubation for Cardiac or Thoracic Surgery (EPITUBE-HEART).

5. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/full/10.1002/ehf2.13893

Norepinephrine use in cardiogenic shock patients is ... The results showed that norepinephrine use was associated with less urine output during the first 24 h in ICU patients with cardiogenic shock ( ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04312971

Norepinephrine Infusion During Cardiopulmonary Bypass The primary objective is to test the efficacy and safety of the accuracy of continuous intravenous infusion of norepinephrine during cardiopulmonary bypass ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9065839/

Norepinephrine use in cardiogenic shock patients is ... As for safety outcomes, cardiac arrest was more common in cardiogenic shock patients with norepinephrine use (OR 2.14, 95% CI 1.25–3.73, P = ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S2666602225000278

The current use of vasoactive agents in cardiogenic shock ... There have been mixed results on efficacy and safety of the administration route of vasoactive agents in CS, and most of the data is derived from observational ...

9. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/full/10.1111/aas.14519

Noradrenaline dose cutoffs to characterise the severity of ... We aimed to identify cutoffs for determining low, intermediate and high doses of noradrenaline (norepinephrine), the primary vasopressor used in intensive care.