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

NCT04391231 | Withdrawn Phase 4 FDA Drug

• 1 other identifier: CSMC - STUDY00000179
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Hemolysis Intravascular; Acute Decompensated Heart Failure

Keywords

CHF; Hemolysis; Impella

Outcome Measures

Primary Outcomes (1)

• Reduction in REBC hemolysis

  Measured by change in plasma free hemoglobin and lactate dehydrogenase levels

  Up to 30 Days post-device implant

Secondary Outcomes (6)

• hemolysis requiring adjustment of device speed settings

  Up to 30 Days post-device implant

• device malfunction

  Up to 30 Days post-device implant

• duration of Impella support

  Up to 30 Days post-device implant

• bleeding

  Up to 30 Days post-device implant

• infection

  Up to 30 Days post-device implant

Study Arms (2)

Pentoxifylline Arm

EXPERIMENTAL

Pentoxifylline (in suspension with SyrSpend SF)

Drug: Pentoxifylline Oral Product

Placebo Arm

PLACEBO COMPARATOR

Placebo (SyrSpend SF only)

Drug: Placebo

Interventions

Pentoxifylline Oral Product DRUG

Blinded Pentoxifylline (in suspension with SyrSpend SF)

Pentoxifylline Arm

Placebo DRUG

Placebo (SyrSpend SF only)

Placebo Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Cedars-Sinai Medical Center: lead

Study Sites (1)

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

Related Publications (8)

• Lima B, Kale P, Gonzalez-Stawinski GV, Kuiper JJ, Carey S, Hall SA. Effectiveness and Safety of the Impella 5.0 as a Bridge to Cardiac Transplantation or Durable Left Ventricular Assist Device. Am J Cardiol. 2016 May 15;117(10):1622-1628. doi: 10.1016/j.amjcard.2016.02.038. Epub 2016 Mar 4.

  PMID: 27061705 BACKGROUND

• 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.

  PMID: 25582036 BACKGROUND

• 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.

  PMID: 26418208 BACKGROUND

• 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.

  PMID: 24418733 BACKGROUND

• 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.

  PMID: 23865494 BACKGROUND

• 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.

  PMID: 23896772 BACKGROUND

• 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.

  PMID: 31156882 BACKGROUND

• 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.

  PMID: 27660567 BACKGROUND

MeSH Terms

Conditions

Hemolysis

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Domininc Emerson, MD

  Cedars-Sinai Medical Center; Smidt Heart Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: This study will be a double-blinded randomized placebo-controlled study.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Staff Physician

Model Details: This study will be a double-blinded randomized placebo-controlled study to determine the efficacy of Pentoxifylline in reducing RBC hemolysis caused by Impella support.

Study Record Dates

• First Submitted: May 7, 2020
• First Posted: May 18, 2020
• Study Start: June 1, 2020
• Primary Completion: June 1, 2022
• Study Completion: June 1, 2022
• Last Updated: May 31, 2025

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)