Hemolysis IntravascularPhase 4NCT04391231
HEMolysis in a Percutaneous Axial Flow LVAD, Effects of Pentoxifylline in a Randomized Controlled Trial
A Phase 4 study testing Pentoxifylline Oral Product in people with Hemolysis Intravascular and Acute Decompensated Heart Failure, run by Cedars-Sinai Medical Center at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hemolysis Intravascular, Acute Decompensated Heart Failure
- What is being tested?
- Pentoxifylline Oral Product
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jun 2020to 1 Jun 2022
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age >/= 18 years of age
- Heart failure patients who undergo axillary Impella 5.0 or 5.5 insertion for acute decompensated heart failure
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Cedars-Sinai Medical Center
Los Angeles, California, 90048
About this study
Official title: HEMolysis in a Percutaneous Axial Flow Left Ventricular Assist Device, Effects of Pentoxifylline in a Randomized Controlled Trial
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.
Read the 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.
- Being tested
- Pentoxifylline Oral Product, Placebo
- Keywords
- CHF, Hemolysis, Impella
- Medical subject headings
- Hemolysis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pentoxifylline Oral ProductDrug
Blinded Pentoxifylline (in suspension with SyrSpend SF)
PlaceboDrug
Placebo (SyrSpend SF only)
| Study group | Role | What they receive |
|---|---|---|
| Pentoxifylline Arm | Experimental | Pentoxifylline (in suspension with SyrSpend SF) Receives: Drug: Pentoxifylline Oral Product |
| Placebo Arm | Placebo comparator | Placebo (SyrSpend SF only) Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Reduction in REBC hemolysis
Measured by change in plasma free hemoglobin and lactate dehydrogenase levels
Measured: Up to 30 Days post-device implant
Secondary outcomes (6)
hemolysis requiring adjustment of device speed settings
Measured by change in plasma free hemoglobin and lactate dehydrogenase levels
Measured: Up to 30 Days post-device implant
device malfunction
Impella system malfunction requiring intervention or device replacement
Measured: Up to 30 Days post-device implant
duration of Impella support
Hours/days of Impella use
Measured: Up to 30 Days post-device implant
bleeding
As assessed by drop in blood count
Measured: Up to 30 Days post-device implant
infection
Assessed by fever and changes in laboratory assessments
Measured: Up to 30 Days post-device implant
death
morbidity from all causes
Measured: Up to 30 Days post-device implant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 May 2020
- Study start1 Jun 2020 (estimated)
- Primary completion1 Jun 2022
- Study completion1 Jun 2022
Why it stopped: Initially the study was underfunded; then, the device we planned to use was changed and the new pump significantly reduced hemolysis.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Hemolysis IntravascularStudies of the same condition, open and under way.
- More trials run by Cedars-Sinai Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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 blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cedars-Sinai Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dominic Emerson, MD, Cedars-Sinai Medical Center
- Investigators
- Domininc Emerson, MD, Principal investigator, Cedars-Sinai Medical Center; Smidt Heart Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04391231
- Sponsor's protocol ID
- CSMC - STUDY00000179
- Status last verified
- Sep 2022
- First submitted
- 7 May 2020
- Last updated
- 31 May 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 27061705Katz 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.
PubMed 25582036Badiye 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.
PubMed 26418208Ravichandran 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.
PubMed 24418733Nielsen 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.
PubMed 23865494Jennings 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.
PubMed 23896772Polonini 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.
PubMed 31156882Bansal 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.
PubMed 27660567
Study at a glance
From the registry record, last updated by the sponsor on 31 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- HEMolysis in a Percutaneous Axial Flow Left Ventricular Assist Device, Effects of Pentoxifylline in a Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT04391231
- Acronym / sponsor ID
- CSMC - STUDY00000179
- Keywords
- CHF, Hemolysis, Impella
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Initially the study was underfunded; then, the device we planned to use was changed and the new pump significantly reduced hemolysis.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Cedars-Sinai Medical CenterUniversity, hospital or other
- Study start
- 1 Jun 2020 (estimated)
- Primary completion
- 1 Jun 2022 (actual)
- Study completion
- 1 Jun 2022 (actual)
- First posted
- 18 May 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| Pentoxifylline Arm | Experimental | Drug: Pentoxifylline Oral ProductPentoxifylline (in suspension with SyrSpend SF) |
| Placebo Arm | Placebo comparator | Drug: PlaceboPlacebo (SyrSpend SF only) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Age >/= 18 years of age
- Heart failure patients who undergo axillary Impella 5.0 or 5.5 insertion for acute decompensated heart failure
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Pentoxifylline Oral ProductBlinded Pentoxifylline (in suspension with SyrSpend SF) | Drug | Pentoxifylline Arm |
| PlaceboPlacebo (SyrSpend SF only) | Drug | Placebo Arm |
Primary outcome
Reduction in REBC hemolysis
Time frame: Up to 30 Days post-device implant
Measured by change in plasma free hemoglobin and lactate dehydrogenase levels
6 secondary outcomes
hemolysis requiring adjustment of device speed settings
Time frame: Up to 30 Days post-device implant
device malfunction
Time frame: Up to 30 Days post-device implant
duration of Impella support
Time frame: Up to 30 Days post-device implant
bleeding
Time frame: Up to 30 Days post-device implant
infection
Time frame: Up to 30 Days post-device implant
death
Time frame: Up to 30 Days post-device implant
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 May 2025.
- Background: PubMed 27061705Lima 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.
- Background: PubMed 25582036Katz 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.
- Background: PubMed 26418208Badiye 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.
- Background: PubMed 24418733Ravichandran 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.
- Background: PubMed 23865494Nielsen 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.
- Background: PubMed 23896772Jennings 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.
- Background: PubMed 31156882Polonini 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.
- Background: PubMed 27660567Bansal 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Domininc Emerson, MD principal investigator
Cedars-Sinai Medical Center; Smidt Heart Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Pentoxifylline Oral Product in people with Hemolysis Intravascular and Acute Decompensated Heart Failure, run by Cedars-Sinai Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 31 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Reduction in REBC hemolysis (time frame: Up to 30 Days post-device implant). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04391231, which also lists 8 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 May 2025.