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Initially the study was underfunded; then, the device we planned to use was changed and the new pump significantly reduced hemolysis.
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Pentoxifylline Arm | Experimental | Pentoxifylline (in suspension with SyrSpend SF) |
|
| Placebo Arm | Placebo Comparator | Placebo (SyrSpend SF only) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Pentoxifylline Oral Product | Drug | Blinded Pentoxifylline (in suspension with SyrSpend SF) |
|
| Measure | Description | Time Frame |
|---|---|---|
| Reduction in REBC hemolysis | Measured by change in plasma free hemoglobin and lactate dehydrogenase levels | Up to 30 Days post-device implant |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| device malfunction | Impella system malfunction requiring intervention or device replacement |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Domininc Emerson, MD | Cedars-Sinai Medical Center; Smidt Heart Institute | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Cedars-Sinai Medical Center | Los Angeles | California | 90048 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 27061705 | Background | 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. | |
| 25582036 | Background |
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| ID | Term |
|---|---|
| D006461 | Hemolysis |
| ID | Term |
|---|---|
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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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.
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This study will be a double-blinded randomized placebo-controlled study.
| Placebo | Drug | Placebo (SyrSpend SF only) |
|
| Up to 30 Days post-device implant |
| duration of Impella support | Hours/days of Impella use | Up to 30 Days post-device implant |
| bleeding | As assessed by drop in blood count | Up to 30 Days post-device implant |
| infection | Assessed by fever and changes in laboratory assessments | Up to 30 Days post-device implant |
| death | morbidity from all causes | Up to 30 Days post-device implant |
| 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. |
| 26418208 | 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. |
| 24418733 | 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. |
| 23865494 | 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. |
| 23896772 | 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. |
| 31156882 | 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. |
| 27660567 | 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. |