HEMolysis in a Percutaneous Axial Flow LVAD, Effects of Pentoxifylline in a Randomized Controlled Trial

NCT ID: NCT04391231

Last Updated: 2025-05-31

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE4
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-06-01
• Study Completion Date: 2022-06-01

Brief Summary

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.

Detailed Description

Subjects will be screened prior to Impella device implant for eligibility. Informed consent will be obtained from eligible subjects. After implant of their Impella Device (5.0/5.5), results of laboratory tests (plasma free hemoglobin & lactate dehydrogenase levels) every 12 hrs for the first 3 days and then daily thereafter. Subjects will receive study medication every 6 hrs from device implant until device explant, death or Day 30 occurs. Impella therapy, concomitant medications and adverse events will be collected until the same. Subjects that don't qualify or opt out of participating will not receive the study medication. The data being collected for the study is based on routine standard of care. The difference between the SOC Impellas subjects and the study patients is the addition of Pentoxifylline being administered along with their SOC medications.

Conditions

Hemolysis Intravascular; Acute Decompensated Heart Failure

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Pentoxifylline Arm

Pentoxifylline (in suspension with SyrSpend SF)

Group Type: EXPERIMENTAL

Pentoxifylline Oral Product

Intervention Type: DRUG

Blinded Pentoxifylline (in suspension with SyrSpend SF)

Placebo Arm

Placebo (SyrSpend SF only)

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo (SyrSpend SF only)

Interventions

Pentoxifylline Oral Product

Blinded Pentoxifylline (in suspension with SyrSpend SF)

Intervention Type: DRUG

Placebo

Placebo (SyrSpend SF only)

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Age >/= 18 years of age
• Heart failure patients who undergo axillary Impella 5.0 or 5.5 insertion for acute decompensated heart failure

Exclusion Criteria

• Concomitant temporary mechanical circulatory support (ECMO, RVAD)
• Heparin induced thrombocytopenia
• Recent cerebral and/or retinal hemorrhage or in patients who have
• Previous intolerance to Pentoxifylline or methylxanthines such as caffeine, theophylline, and theobromine
• Women who are currently pregnant, nursing or planning on becoming pregnant.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Cedars-Sinai Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Dominic Emerson, MD

Staff Physician

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Domininc Emerson, MD

Role: PRINCIPAL_INVESTIGATOR

Cedars-Sinai Medical Center; Smidt Heart Institute

Locations

Cedars-Sinai Medical Center

Los Angeles, California, United States

Countries

United States

References

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Reference Type: BACKGROUND

PMID: 27061705 (View on PubMed)

Katz JN, Jensen BC, Chang PP, Myers SL, Pagani FD, Kirklin JK. A multicenter analysis of clinical hemolysis in patients supported with durable, long-term left ventricular assist device therapy. J Heart Lung Transplant. 2015 May;34(5):701-9. doi: 10.1016/j.healun.2014.10.002. Epub 2014 Nov 4.

Reference Type: BACKGROUND

PMID: 25582036 (View on PubMed)

Badiye AP, Hernandez GA, Novoa I, Chaparro SV. Incidence of Hemolysis in Patients with Cardiogenic Shock Treated with Impella Percutaneous Left Ventricular Assist Device. ASAIO J. 2016 Jan-Feb;62(1):11-4. doi: 10.1097/MAT.0000000000000290.

Reference Type: BACKGROUND

PMID: 26418208 (View on PubMed)

Ravichandran AK, Parker J, Novak E, Joseph SM, Schilling JD, Ewald GA, Silvestry S. Hemolysis in left ventricular assist device: a retrospective analysis of outcomes. J Heart Lung Transplant. 2014 Jan;33(1):44-50. doi: 10.1016/j.healun.2013.08.019. Epub 2013 Nov 14.

Reference Type: BACKGROUND

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Nielsen VG, Pearson EC, Smith MC. Increased carbon monoxide production by hemeoxygenase-1 caused by device-mediated hemolysis: thrombotic phantom menace? Artif Organs. 2013 Nov;37(11):1008-14. doi: 10.1111/aor.12122. Epub 2013 Jul 19.

Reference Type: BACKGROUND

PMID: 23865494 (View on PubMed)

Jennings DL, Williams CT, Morgan JA. Pentoxifylline for the treatment of hemolytic anemia in a patient who developed recurrent gastrointestinal bleeding while on continuous-flow left ventricular assist device support. ASAIO J. 2013 Sep-Oct;59(5):526-7. doi: 10.1097/MAT.0b013e31829f0eb1.

Reference Type: BACKGROUND

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Polonini HC, Silva SL, de Almeida TR, Brandao MAF, Ferreira AO. Compatibility of caffeine, carvedilol, clomipramine hydrochloride, folic acid, hydrochlorothiazide, loperamide hydrochloride, methotrexate, nadolol, naltrexone hydrochloride and pentoxifylline in SyrSpend SF PH4 oral suspensions. Eur J Hosp Pharm. 2016 Nov;23(6):352-358. doi: 10.1136/ejhpharm-2016-000903. Epub 2016 Mar 24.

Reference Type: BACKGROUND

PMID: 31156882 (View on PubMed)

Bansal A, Bhama JK, Patel R, Desai S, Mandras SA, Patel H, Collins T, Reilly JP, Ventura HO, Parrino PE. Using the Minimally Invasive Impella 5.0 via the Right Subclavian Artery Cutdown for Acute on Chronic Decompensated Heart Failure as a Bridge to Decision. Ochsner J. 2016 Fall;16(3):210-6.

Reference Type: BACKGROUND

PMID: 27660567 (View on PubMed)

Other Identifiers

CSMC - STUDY00000179

Identifier Type: -

Identifier Source: org_study_id