Pentoxifylline for Heart Failure

Overseen By Dominic Emerson, MD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Cedars-Sinai Medical Center

Must not be taking: Methylxanthines

Disqualifiers: ECMO, RVAD, Heparin intolerance, others

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

Compensation: Varies

Number of Visits: 13

Duration: Up to 30 days

Trial Summary

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 evidence supports the effectiveness of the drug pentoxifylline for heart failure?

Research shows that pentoxifylline can improve heart function by increasing cardiac output (the amount of blood the heart pumps) and reducing vascular resistance (the force against which the heart must pump) in patients with heart failure. Additionally, it has been beneficial in patients with idiopathic dilated cardiomyopathy, a type of heart disease, when used alongside other heart medications. ^{1 2 3 4 5}

Is pentoxifylline safe for humans?

Pentoxifylline has been studied in people with heart failure and other heart conditions, and it is generally considered safe. It has anti-inflammatory effects and has been used to improve heart function, but its safety in advanced heart failure is not fully determined. ^{3 6 7 8 9}

How does the drug Pentoxifylline differ from other heart failure treatments?

Pentoxifylline is unique because it is primarily used to improve blood flow by reducing blood viscosity (thickness), which can help in conditions like peripheral artery disease. This mechanism might offer a novel approach for heart failure treatment compared to traditional drugs that focus on heart muscle contraction or blood pressure regulation. ^{10 11 12 13 14}

What is the purpose of this trial?

Temporary mechanical circulatory support devices are increasingly used for short-term support in patients with decompensated cardiogenic shock. Recently, a new axial flow pump has become widely available with the Impella System. The Impella has been FDA approved for short term usage. Hemolysis, however, has been a common complication that has increased morbidity and mortality in this patient population. It is hypothesized that a major source of hemolysis in this patient population is shear stress experienced by red blood cells (RBC) as they travel through the pump device. In addition to causing RBC loss and potential anemia, the hemolysis has multiple other downstream consequences including creation of a pro-thrombotic environment leading to clot formation and potential device failure and secondary end organ dysfunction (renal and liver failure). Due to the significant effects of hemolysis in this population, a great deal of interest has been recently focused on addressing this problem, but as of yet no durable solutions exist. Pentoxifylline improves red blood cell deformability and reduces blood viscosity. It is hypothesized here that administering Pentoxifylline to patients in CS who require temporary MCS will decrease the amount of shear stress related hemolysis through the improved deformability and durability of RBCs. We propose to perform a double-blinded randomized controlled trial in patients who undergo an axillary Impella 5.0 insertion for acute decompensated heart failure. There will be a control group who receives a placebo and the treatment group who receives pentoxifylline. Labs will be drawn to monitor hemolysis which is our current standard protocol for the life of the device to determine the efficacy of pentoxifylline in decreasing hemolysis in this patient population.

Research Team

Domininc Emerson, MD

Principal Investigator

Cedars-Sinai Medical Center; Smidt Heart Institute

Eligibility Criteria

This trial is for adults over 18 with heart failure who are getting an Impella device inserted due to acute decompensated heart failure. It's not for those who've had recent brain or eye bleeding, pregnant or nursing women, people allergic to Pentoxifylline or similar stimulants, have a specific blood platelet condition (HIT), or are on other mechanical circulatory support.

Inclusion Criteria

I have heart failure and had an Impella device inserted for worsening symptoms.

Exclusion Criteria

I am not pregnant, nursing, or planning to become pregnant.

Concomitant temporary mechanical circulatory support (ECMO, RVAD)

I have had a recent brain or eye bleed.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Treatment

Participants receive either Pentoxifylline or placebo every 6 hours from device implant until device explant, death, or Day 30

Up to 30 days

Continuous monitoring with lab tests every 12 hours for the first 3 days, then daily

Follow-up

Participants are monitored for safety and effectiveness after treatment, including device malfunction, bleeding, and infection

Up to 30 days post-device implant

Treatment Details

Interventions

• Pentoxifylline Oral Product
• Placebo

Trial Overview The study tests if Pentoxifylline can reduce red blood cell damage caused by the Impella heart pump in patients with cardiogenic shock. Participants will be randomly assigned to receive either Pentoxifylline or a placebo while their hemolysis levels are monitored.

Participant Groups

Group I: Pentoxifylline Arm Experimental Treatment 1 Intervention

Pentoxifylline (in suspension with SyrSpend SF)

Group II: Placebo Arm Placebo Group 1 Intervention

Placebo (SyrSpend SF only)

Who Is Running the Clinical Trial?

Cedars-Sinai Medical Center

Lead Sponsor

Trials

523

Recruited

165,000+

Findings from Research

ACE inhibitors are the most effective class of drugs for improving survival in chronic heart failure patients, regardless of the disease stage, and are currently being studied for their dose-effect relationship.

While beta-blockers enhance quality of life and physical performance, they have not shown a mortality benefit, and phosphodiesterase inhibitors, despite improving quality of life, are associated with increased mortality and are not recommended for heart failure treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Treatment of chronic heart failure: current views]. Komajda, M.[2009]

References

1. Hungary pubmed.ncbi.nlm.nih.gov

Immunological aspects of the effect of pentoxifylline (Trental) (a brief review). [2020]

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

Beneficial effects of pentoxifylline in patients with idiopathic dilated cardiomyopathy treated with angiotensin-converting enzyme inhibitors and carvedilol: results of a randomized study. [2019]

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

Pentoxifylline in heart failure: a meta-analysis of clinical trials. [2014]

4. Sweden pubmed.ncbi.nlm.nih.gov

Effects of pentoxifylline on central hemodynamics in patients with congestive heart failure. [2019]

5. Germany pubmed.ncbi.nlm.nih.gov

The effect of pentoxifylline on central and peripheral haemodynamics--an experimental clinical study. [2007]

6. England pubmed.ncbi.nlm.nih.gov

Randomised investigation of effects of pentoxifylline on left-ventricular performance in idiopathic dilated cardiomyopathy. [2015]

7. South Africa pubmed.ncbi.nlm.nih.gov

Pentoxifylline for heart failure: a systematic review. [2018]

8. England pubmed.ncbi.nlm.nih.gov

Pentoxifylline in ischemic, hypertensive and idiopathic-dilated cardiomyopathy: effects on left-ventricular function, inflammatory cytokines and symptoms. [2013]

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

Effects of pentoxifylline on cytokine profiles and left ventricular performance in patients with decompensated congestive heart failure secondary to idiopathic dilated cardiomyopathy. [2019]

10. Germany pubmed.ncbi.nlm.nih.gov

[Vasodilatation and positive inotropic effect of the phosphodiesterase inhibitor enoximone]. [2013]

11. England pubmed.ncbi.nlm.nih.gov

Extended-Release Oral Milrinone for the Treatment of Heart Failure With Preserved Ejection Fraction. [2021]

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

Chronic therapy of severe heart failure with enoximone. [2013]

13. France pubmed.ncbi.nlm.nih.gov

[Treatment of chronic heart failure: current views]. [2009]

14. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Potentialitis of phosphodiesterase inhibitors in management of patients with chronic heart failure complicating cardiac ischemia]. [2016]