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

Acute Decompensated Heart Failure Clinical Trial

Official title:

HEMolysis in a Percutaneous Axial Flow Left Ventricular Assist Device, Effects of Pentoxifylline in a Randomized Controlled Trial

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04391231
• Other study ID #: CSMC - STUDY00000179
• Status: Not yet recruiting
• Phase: Phase 4
• Start date: September 15, 2021
• Est. completion date: June 1, 2027

Study information

• Verified date: August 2021
• Source: Cedars-Sinai Medical Center
• Contact: Dominic Emerson, MD
• Phone: 310.423.3300
• Email: dominic.emerson[@]cshs.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 50
• Est. completion date: June 1, 2027
• Est. primary completion date: June 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Acute Decompensated Heart Failure
• Hemolysis
• Hemolysis Intravascular

Intervention

Drug:
• Pentoxifylline Oral Product
Blinded Pentoxifylline (in suspension with SyrSpend SF)
• Placebo
Placebo (SyrSpend SF only)

Locations

Country	Name	City	State
United States	Cedars-Sinai Medical Center	Los Angeles	California

Sponsors (1)

Lead Sponsor	Collaborator
Cedars-Sinai Medical Center

Country where clinical trial is conducted

United States, 

References & Publications (8)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. Review. — View Citation

Polonini HC, Silva SL, de Almeida TR, Brandão 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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Reduction in REBC hemolysis	Measured by change in plasma free hemoglobin and lactate dehydrogenase levels	Up to 30 Days post-device implant
Secondary	hemolysis requiring adjustment of device speed settings	Measured by change in plasma free hemoglobin and lactate dehydrogenase levels	Up to 30 Days post-device implant
Secondary	device malfunction	Impella system malfunction requiring intervention or device replacement	Up to 30 Days post-device implant
Secondary	duration of Impella support	Hours/days of Impella use	Up to 30 Days post-device implant
Secondary	bleeding	As assessed by drop in blood count	Up to 30 Days post-device implant
Secondary	infection	Assessed by fever and changes in laboratory assessments	Up to 30 Days post-device implant
Secondary	death	morbidity from all causes	Up to 30 Days post-device implant