Phenylephrine for Mitral Valve Regurgitation

Overseen By Mario Garcia, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Montefiore Medical Center

Disqualifiers: Heart failure, Coronary artery disease, Arrhythmias, Hypertension, others

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

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

Compensation: Varies

Number of Visits: 1

Duration: 40 minutes

35 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called phenylephrine to determine if it can help doctors better assess the severity of mitral valve regurgitation (a heart valve issue where blood flows backward) during a special heart test. The goal is to align the test results more closely with everyday activities, enabling doctors to make better treatment decisions. Individuals diagnosed with mitral valve regurgitation and already scheduled for a transesophageal echocardiogram (TEE) might be suitable candidates for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to contribute to groundbreaking medical 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.

What prior data suggests that this phenylephrine protocol is safe for use during transesophageal echocardiography?

Studies have shown that phenylephrine can raise blood pressure, even with just one dose. This is important because higher blood pressure can affect the heart. Research suggests that individuals with certain conditions, such as heart issues or low blood volume, should exercise caution when using phenylephrine. It can also cause other heart-related side effects, especially in high doses or in sensitive individuals.

Phenylephrine is often found in cold medicines to help clear stuffy noses by narrowing blood vessels. This action may also alter blood flow in other parts of the body. Overall, while phenylephrine is generally safe for many, those with heart problems should remain cautious. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard treatments for mitral valve regurgitation, which often involve surgery or other medications like ACE inhibitors and beta-blockers, phenylephrine offers a unique approach by acting as a vasoconstrictor. This means it works by narrowing blood vessels and potentially reducing the backward flow of blood through the mitral valve. Researchers are excited about phenylephrine because its fast-acting nature could offer quicker symptomatic relief compared to existing treatments. Additionally, its administration as an intravascular bolus allows for precise control over dosage, which might lead to better management of acute symptoms.

What evidence suggests that this phenylephrine protocol is effective for mitral valve regurgitation?

Research has shown that phenylephrine, which participants in this trial will receive, can help evaluate mitral valve regurgitation (MR), a condition where the heart's mitral valve doesn't close tightly, causing blood to flow backward. One study found that phenylephrine reduced the severity of MR from an average grade of 4.60 (moderate/severe) to 2.06 (mild/moderate). This treatment increases the resistance the heart faces when pumping blood, similar to normal physical activity, aiding doctors in assessing MR severity. Additionally, phenylephrine narrows blood vessels, helping to maintain stable blood pressure during medical procedures, making it useful in surgeries. ^{6 7 8 9 10}

Who Is on the Research Team?

Mario Garcia, MD

Principal Investigator

Montefiore Medical Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 with Mitral Regurgitation (MR) detected on an initial heart scan, who are fit for a more detailed heart scan called transesophageal echocardiography (TEE). People with unstable heart conditions, severe artery disease, recent strokes or high blood pressure aren't eligible.

Inclusion Criteria

I am 18 or older and have mitral regurgitation, scheduled for a TEE test.

Exclusion Criteria

I have a slow heartbeat (below 50 beats per minute) or heart block.

My blood pressure is not higher than 150/90 mmHg.

My blood pressure is not above 100 mmHg and I don't have severe heart valve leakage.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Administration of phenylephrine during transesophageal echocardiography to assess mitral regurgitation severity

40 minutes

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Phenylephrine

Trial Overview

The study tests the use of Mydfrin (phenylephrine) during TEE to increase afterload and mimic normal physical stress. This aims to better assess MR severity by observing changes in its grade under these simulated conditions, which could improve clinical decisions.

How Is the Trial Designed?

Group I: Mydfrin Experimental Treatment 1 Intervention

Phenylephrine is available as phenylephrine hydrochloride injection, 10 mg/mL in 1 mL vial. For intravascular bolus administration, the investigators will prepare a solution containing 100 mcg/mL of phenylephrine hydrochloride, by withdrawing 10 mg (1ml of 10mg/mL) of phenylephrine injection and diluting with 99 mL of 5% dextrose injection or 0.9% sodium chloride injection.

Who Is Running the Clinical Trial?

Montefiore Medical Center

Lead Sponsor

Trials

468

Recruited

599,000+

Baylor College of Medicine

Collaborator

Trials

1,044

Recruited

6,031,000+

Published Research Related to This Trial

A case study of an atopic woman revealed that she experienced type IV hypersensitivity reactions, including nasal congestion and difficulty breathing, after using products containing phenylephrine, indicating a potential allergic response to this sympathomimetic agent.

Patch testing confirmed the patient's sensitivity to phenylephrine and its cross-reactivity with ethylephrine, marking the first documented instance of such a reaction to nasally administered phenylephrine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Type IV reaction due to phenylephrine administered nasally with cross-reactivity with ethylephrine. Bobadilla-González, P., Pérez-Rangel, I., García-Menaya, JM., et al.[2013]

In a study of 34 patients undergoing coronary artery bypass grafting (CABG), both milrinone and olprinone were found to effectively improve cardiac function and hemodynamics without causing significant hypotension when used with low-dose catecholamines.

Olprinone was particularly effective in reducing pressures in the aorta and pulmonary artery, as well as decreasing heart preload compared to milrinone, suggesting its potential benefits in managing post-cardiotomy cardiogenic shock.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of phosphodiesterase inhibitors after coronary artery bypass grafting. Orime, Y., Shiono, M., Hata, H., et al.[2019]

In a study of 288 hospitalized patients with congestive heart failure, those treated with milrinone experienced a higher incidence of major adverse cardiovascular and cerebrovascular events (MACCE) and cardiac death compared to those treated with olprinone, indicating milrinone may be less safe for these patients.

Milrinone was identified as an independent predictor of MACCE and cardiac death, particularly in patients with ischemic heart disease and chronic kidney disease, suggesting that olprinone may be a better option for managing CHF in these populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparing the effects of milrinone and olprinone in patients with congestive heart failure. Dobashi, S., Watanabe, I., Nakanishi, R., et al.[2020]

In a study of 25 patients undergoing mitral valve surgery, enoximone was found to be a highly effective first-line inotropic agent, successfully weaning all patients from cardiopulmonary bypass with significant improvements in cardiac index and stroke index without increasing heart rate.

Compared to dobutamine and dopamine, enoximone demonstrated superior hemodynamic effects, with fewer patients experiencing inadequate responses, highlighting its advantages in managing post-operative low output states.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Haemodynamic effects and comparison of enoximone, dobutamine and dopamine following mitral valve surgery. Tarr, TJ., Moore, NA., Frazer, RS., et al.[2013]

In a study of 40 patients with low cardiac output after mitral valve surgery, both Dobutamine and Enoximone significantly improved cardiac function, with similar increases in cardiac index (55% for Enoximone and 59% for Dobutamine) within two hours of treatment.

Enoximone was associated with a shorter treatment duration (59 hours) and reduced intensive care unit stay (92 hours) compared to Dobutamine (86 hours and 155 hours, respectively), suggesting it may be a more efficient option for managing low cardiac output states.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Comparison of the hemodynamic effects of dobutamine and enoximone in the treatment of low cardiac output after valvular surgery]. George, M., Atallah, G., Lehot, JJ., et al.[2013]

Phenylephrine (PE) is an ineffective substitute for pseudoephedrine (PDE) as a nasal decongestant, as it is poorly absorbed and its efficacy is unproven, despite both having good safety records.

Restricting the sale of PDE has not significantly reduced methamphetamine abuse or related arrests, suggesting that these restrictions may unnecessarily limit access to an effective treatment for nasal congestion.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Substitution of phenylephrine for pseudoephedrine as a nasal decongeststant. An illogical way to control methamphetamine abuse. Eccles, R.[2018]

In a case study of a 58-year-old woman with mitral regurgitation undergoing valve repair or replacement, careful anesthetic management was crucial, involving graded induction and the use of medications like isoflurane and phenylephrine to maintain stable cardiovascular parameters.

Milrinone was effectively used for inotropic support due to its vasodilator properties, which helped improve blood flow while minimizing pulmonary hypertension, highlighting the importance of tailored anesthetic strategies in patients with mitral regurgitation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mitral valve replacement: a case report. Reckard, D., Cipcic, E., Mackin, C.[2012]

In a study of five patients with severe pulmonary hypertension and right heart failure after mitral valve replacement, high-dose prostaglandin E1 effectively reduced pulmonary vasoconstriction and improved right ventricular function.

The combination of prostaglandin E1 with norepinephrine helped maintain blood pressure while enhancing pulmonary vasodilation, leading to successful recovery without any cases of right ventricular infarction or chronic heart failure post-surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prostaglandin E1. A new therapy for refractory right heart failure and pulmonary hypertension after mitral valve replacement. D'Ambra, MN., LaRaia, PJ., Philbin, DM., et al.[2013]

Milrinone effectively relaxes constricted tracheal spirals, lung parenchymal strips, and pulmonary artery rings, with IC50 values indicating it is less potent than isoproterenol but more potent than aminophylline in these effects.

The relaxant effects of milrinone are not influenced by common receptor blockers, suggesting a unique mechanism of action, particularly as indomethacin blocked its effects on tracheal spirals, indicating different modes of action across tissue types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of milrinone on contractile responses of guinea pig trachea, lung parenchyma and pulmonary artery. Rossing, TH., Drazen, JM.[2015]

A review of 12 clinical studies found that intranasal phenylephrine appears to be safe for patients with controlled hypertension, based on one double-blind randomized trial.

The evidence regarding the safety of other sympathomimetic decongestants like phenylpropanolamine and pseudoephedrine in hypertensive patients is limited and unclear, suggesting that the belief they are unsafe is not strongly supported by research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Are oral decongestants safe in hypertension? An evaluation of the evidence and a framework for assessing clinical trials. Radack, K., Deck, CC.[2013]

A pilot experienced postural hypotension as a side effect of taking pseudoephedrine (Sudafed), highlighting the risks associated with self-medication for upper respiratory symptoms.

This case serves as a warning for flight crew members about the potential hazards of using over-the-counter medications like pseudoephedrine, which can impair their ability to safely perform their duties.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pseudoephedrine producing postural hypotension in a pilot. Beary, JF.[2013]

Milrinone effectively reduced pulmonary artery pressure and increased cardiac output in a 65-year-old female patient with mitral regurgitation and severe pulmonary hypertension, allowing for safe mitral valve surgery.

The use of milrinone not only helped manage the patient's pulmonary hypertension but also served as a valuable tool in assessing the reversibility of the condition prior to surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The use of milrinone in a patient with mitral regurgitation and severe pulmonary hypertension: a case report]. Yamada, T., Katori, N., Tagawa, M., et al.[2013]

An 18-year-old woman experienced two distinct allergic reactions to phenylephrine and pseudoephedrine, suggesting that while both drugs belong to the same family, they may not necessarily cause cross-reactive allergic responses.

Patch testing confirmed that the patient's reactions were specifically linked to phenylephrine and pseudoephedrine, highlighting the importance of individual drug testing in cases of suspected drug allergies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Erythrodermia to pseudoephedrine in a patient with contact allergy to phenylephrine. Gonzalo-Garijo, MA., Pérez-Calderón, R., de Argila, D., et al.[2019]

Citations

1.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/16950471/

Intraoperative assessment of mitral regurgitation

Objectives: We defined the effects of the operative (OP) state and phenylephrine challenge on the assessment of mitral regurgitation (MR) severity.

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8394282/

Phenylephrine provocation to evaluate the etiology of mitral ...

Phenylephrine administration resulted in a change from average baseline MR severity grade of 4.60 ± 0.12 (moderate/severe) to 2.06 ± 0.17 (mild/moderate) with a ...

3.

clinicaltrials.gov

clinicaltrials.gov/study/NCT04500899

Study Details | NCT04500899 | Use of Phenylephrine for ...

The study proposes to develop a phenylephrine protocol to be used during transesophageal echocardiography, whereby intravenous phenylephrine would be used ...

4.

withpower.com

withpower.com/trial/phase-2-mitral-valve-insufficiency-11-2020-46681

Phenylephrine for Mitral Valve Regurgitation

Phenylephrine is unique in its use for mitral valve regurgitation as it is primarily a vasoconstrictor, which helps maintain blood pressure during surgery, ...

5.

sciencedirect.com

sciencedirect.com/science/article/pii/S2957391224000561

Substantial challenge for a patient with severe mitral ...

We present a case highlighting 2 distinctive intraoperative events of a patient with severe mitral regurgitation and pulmonary hypertension undergoing the TEER ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC4500855/

simulation and narrative review

It has been estimated that a 20-mmHg increase in systolic blood pressure would occur with an oral dose of 45 mg phenylephrine in normotensive healthy people.

7.

ahajournals.org

ahajournals.org/doi/10.1161/cir.0000000000000426

Drugs That May Cause or Exacerbate Heart Failure

Risk factors consist of older age, female sex, longer duration of therapy (3 months–27 years; mean >10 years), elevated milligram per kilogram daily dose, ...

8.

drugs.com

drugs.com/disease-interactions/phenylephrine,sudafed-pe-congestion.html?professional=1

Sudafed PE Congestion Disease Interactions

Sympathomimetic agents may cause adverse cardiovascular effects, particularly when used in high dosages and/or in susceptible patients.

9.

heart.org

heart.org/en/news/2019/01/18/taking-medicine-for-a-cold-be-mindful-of-your-heart

Taking medicine for a cold? Be mindful of your heart.

Decongestants – like pseudoephedrine or phenylephrine – constrict blood vessels. They allow less fluid into your sinuses, "which dries you up," ...

10.

ncbi.nlm.nih.gov

ncbi.nlm.nih.gov/books/NBK534801/

Phenylephrine - StatPearls - NCBI Bookshelf - NIH

Contraindications · Phenylephrine use warrants caution in patients with a history of bradycardia, severe cardiac dysfunction, and hypovolemia.