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

Trial Summary

What is the purpose of this trial?

The study proposes to develop a phenylephrine protocol to be used during transesophageal echocardiography, whereby intravenous phenylephrine would be used to increase afterload with the intent to mimic the awake hemodynamic profile and variation that occurs with normal physical activity. The expectation is to see changes in severity of Mitral Regurgitation (MR) grade with increasing afterload, which in turn can provide more accurate quantification of MR severity to assist in clinical decision making.

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 drug Phenylephrine for Mitral Valve Regurgitation?

The research does not provide direct evidence for the effectiveness of Phenylephrine in treating Mitral Valve Regurgitation. However, one case report mentions the use of Phenylephrine to maintain stable cardiovascular parameters during mitral valve surgery, suggesting it may help manage blood pressure in this context. ^{1 2 3 4 5}

Is phenylephrine generally safe for humans?

Phenylephrine is generally considered safe for humans, but it can cause rare allergic reactions and should be used cautiously in people with high blood pressure. It has a good safety record when used as a nasal decongestant. ^{6 7 8 9 10}

How does phenylephrine differ from other drugs 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, unlike other treatments like milrinone that focus on vasodilation and increasing cardiac output. ^{3 5 11 12 13}

Research Team

Mario Garcia, MD

Principal Investigator

Montefiore Medical Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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 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]

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]

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]

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]

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]

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]

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]

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]

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]

References

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

Haemodynamic effects and comparison of enoximone, dobutamine and dopamine following mitral valve surgery. [2013]

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

Prostaglandin E1. A new therapy for refractory right heart failure and pulmonary hypertension after mitral valve replacement. [2013]

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

Mitral valve replacement: a case report. [2012]

4. France pubmed.ncbi.nlm.nih.gov

[Comparison of the hemodynamic effects of dobutamine and enoximone in the treatment of low cardiac output after valvular surgery]. [2013]

5. Japan pubmed.ncbi.nlm.nih.gov

Effects of phosphodiesterase inhibitors after coronary artery bypass grafting. [2019]

6. Spain pubmed.ncbi.nlm.nih.gov

Type IV reaction due to phenylephrine administered nasally with cross-reactivity with ethylephrine. [2013]

7. Singapore pubmed.ncbi.nlm.nih.gov

Erythrodermia to pseudoephedrine in a patient with contact allergy to phenylephrine. [2019]

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

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

9. England pubmed.ncbi.nlm.nih.gov

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

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

Pseudoephedrine producing postural hypotension in a pilot. [2013]

11. Japan pubmed.ncbi.nlm.nih.gov

[The use of milrinone in a patient with mitral regurgitation and severe pulmonary hypertension: a case report]. [2013]

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

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

13. Japan pubmed.ncbi.nlm.nih.gov

Comparing the effects of milrinone and olprinone in patients with congestive heart failure. [2020]