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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Hemolysis Intravascular, Acute Decompensated Heart Failure

Intervention / Treatment
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* Drug: Pentoxifylline Oral Product
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 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.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pentoxifylline Arm<br>Pentoxifylline (in suspension with SyrSpend SF) | Drug: Pentoxifylline Oral Product<br>* Blinded Pentoxifylline (in suspension with SyrSpend SF)<br>|
| Placebo Comparator: Placebo Arm<br>Placebo (SyrSpend SF only) | Drug: Placebo<br>* Placebo (SyrSpend SF only)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | 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 | 

Secondary Outcome Measures

| Outcome Measure | 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 | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CHF, Hemolysis, Impella