LVAD Conditioning for Heart Failure

Overseen By John Kirk

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: STAVROS G DRAKOS

Disqualifiers: Adverse events, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores ways to improve heart function in individuals with severe heart failure who use a Left Ventricular Assist Device (LVAD). Researchers will adjust the LVAD to encourage the heart to work slightly harder, potentially improving heart health and quality of life. This trial is ideal for patients with an implanted LVAD who are awaiting a heart transplant. As an unphased trial, it offers patients a unique opportunity to contribute to innovative research that could enhance their heart health and quality of life.

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications.

What prior data suggests that this myocardial conditioning protocol is safe for heart failure patients?

Research has shown that Left Ventricular Assist Devices (LVADs) can extend the lives of people with heart failure, though they carry risks such as strokes and other serious issues. Many studies have also found that LVADs might improve heart failure, with some patients eventually discontinuing use after their heart function improved.

The treatment under investigation is called LVAD conditioning, which involves adjusting the LVAD speed to help the heart gradually work harder. While the devices have known risks, the conditioning process aims to carefully manage the heart's workload. Specific data on the safety of this conditioning method is not yet available, but since LVADs are already approved and used for heart failure, some safety evidence exists from their general use. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about LVAD Conditioning for heart failure because it offers a new approach to managing the condition. Unlike traditional treatments that primarily focus on medication or device implantation to support heart function, LVAD Conditioning involves adjusting the device's speed to gradually "reload" the heart. This controlled cardiac reloading could potentially help the heart regain some of its natural function, which is a significant shift from merely providing mechanical support. This process might improve heart health in the long term and reduce dependency on the device, offering hope for better outcomes for heart failure patients.

What evidence suggests that LVAD conditioning is effective for heart failure?

Research has shown that LVADs, devices that assist the heart in pumping blood, can enhance heart function in individuals with severe heart failure. In this trial, participants will undergo myocardial conditioning, a process where researchers adjust the LVAD speed. This method aims to gradually increase the heart's workload, potentially aiding the heart in recovering and functioning independently. Some patients have reduced their reliance on these devices. Although using LVADs carries some risks, this conditioning method appears promising for improving recovery and quality of life. ^{2 3 4 6 7}

Who Is on the Research Team?

Stavros Drakos, MD

Principal Investigator

University of Utah

Are You a Good Fit for This Trial?

This trial is for heart failure patients who are getting an LVAD implant as a temporary step before a transplant. They must be part of another study (IRB 30622) and able to give consent. People who don't understand English or have been hospitalized due to complications during earlier treatment phases cannot join.

Inclusion Criteria

Enrolled in the Effects of Mechanical Unloading on Myocardial Function and Structure study (IRB 30622)

I am diagnosed with heart failure and will get an LVAD before a transplant.

Exclusion Criteria

I or my representative do not understand spoken English.

Neither the subject nor the subject's representative is willing to provide written consent for participation

I was not hospitalized due to side effects during the initial treatment phase.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Optimum Unloading Phase

Heart failure patients undergo an optimum unloading phase with LVAD support to stabilize their condition before controlled reloading

Varies

Controlled Cardiac Reloading

Participants undergo controlled cardiac reloading through LVAD speed adjustment reductions to promote myocardial recovery

Up to 12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, including heart tissue analysis and echocardiography

12 months

What Are the Treatments Tested in This Trial?

Interventions

• LVAD Conditioning

Trial Overview The study tests if adjusting the speed of the LVAD can help improve heart function by gradually increasing the heart's workload. This method, known as myocardial conditioning, could potentially enhance quality of life for those with severe heart failure.

How Is the Trial Designed?

Group I: Controlled Cardiac Reloading Experimental Treatment 1 Intervention

Heart failure patients with recent LVAD implantation after an optimum unloading phase, will undergo controlled cardiac reloading through LVAD speed adjustment reductions in a controlled reloading phase

LVAD Conditioning is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Left Ventricular Assist Device for:

• Advanced heart failure
• Bridge to transplant
• Destination therapy

Approved in United States as Left Ventricular Assist Device for:

• Advanced heart failure
• Bridge to transplant
• Destination therapy

Approved in Canada as Left Ventricular Assist Device for:

• Advanced heart failure
• Bridge to transplant
• Destination therapy

Approved in Japan as Left Ventricular Assist Device for:

• Advanced heart failure
• Bridge to transplant
• Destination therapy

Who Is Running the Clinical Trial?

STAVROS G DRAKOS

Lead Sponsor

Trials

3

Recruited

600+

American Heart Association

Collaborator

Trials

352

Recruited

6,196,000+

Published Research Related to This Trial

In a study of 6205 patients with centrifugal-flow left ventricular assist devices, the Abbott HeartMate3 (HM3) showed a significantly lower incidence of major neurologic adverse events (NAEs) compared to the Medtronic HeartWare HVAD, with rates of 6.4% versus 16.4%, respectively.

The increased risk of NAEs with the HVAD persisted beyond the early post-implantation period, indicating that patients with this device had a 5.71 times higher hazard of experiencing major NAEs during the constant hazard phase compared to those with the HM3.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cerebrovascular Events in Patients With Centrifugal-Flow Left Ventricular Assist Devices: Propensity Score-Matched Analysis From the Intermacs Registry. Cho, SM., Mehaffey, JH., Meyers, SL., et al.[2021]

In a study of 9,489 patients receiving continuous flow left ventricular assist devices (LVADs), 16% experienced strokes within the first two years, with significant mortality risks associated with both ischemic and hemorrhagic strokes.

The study found that disabling strokes led to a much higher mortality rate, with only 70% survival after an ischemic stroke and less than 50% after a hemorrhagic stroke, highlighting the critical need for effective stroke prevention strategies in LVAD patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quantifying the impact from stroke during support with continuous flow ventricular assist devices: An STS INTERMACS analysis. Kirklin, JK., Naftel, DC., Myers, SL., et al.[2021]

In a study of 430 patients implanted with left ventricular assist devices (LVADs) in the Netherlands, long-term survival rates were over 50% after 5 years, with better outcomes for those receiving the device as a bridge to transplant compared to destination therapy.

Major adverse events, particularly infections and bleeding, were common but showed a decrease with the use of the HeartMate 3 LVAD, indicating improvements in safety with contemporary devices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Left ventricular assist device implantation and clinical outcomes in the Netherlands. Damman, K., Caliskan, K., Birim, O., et al.[2023]

Patients with end-stage renal disease (ESRD) who received left ventricular assist devices (LVADs) had a significantly higher risk of death compared to those without ESRD, with 81.9% of ESRD patients dying during follow-up, often within just 16 days after surgery.

The study highlights the extremely poor prognosis for ESRD patients undergoing LVAD placement, emphasizing the need for careful consideration and shared decision-making regarding treatment options for advanced heart failure in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes Associated With Left Ventricular Assist Devices Among Recipients With and Without End-stage Renal Disease. Bansal, N., Hailpern, SM., Katz, R., et al.[2019]

Left ventricular assist devices (LVADs) have significantly improved the quality of life and long-term survival rates for patients with heart failure, addressing a critical health issue.

The latest LVAD models are designed to be smaller and more efficient, leading to fewer adverse events and better durability, but careful patient selection is essential for achieving the best outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Challenges and Future Directions in Left Ventricular Assist Device Therapy. Kanwar, MK., Bailey, S., Murali, S.[2018]

A study of 26 patients who underwent LVAD explantation showed that using a standardized weaning protocol and a minimally invasive technique resulted in good long-term survival rates, with 88% survival at 1 year and 77% at 6 years.

The average left ventricular ejection fraction improved to 44.25% one year after explantation, indicating potential myocardial recovery in patients after long-term LVAD support.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A detailed explantation assessment protocol for patients with left ventricular assist devices with myocardial recovery. Monteagudo Vela, M., Rial Bastón, V., Panoulas, V., et al.[2022]

In a study of 6205 patients with centrifugal-flow left ventricular assist devices, the Abbott HeartMate3 (HM3) showed a significantly lower incidence of major neurologic adverse events (NAEs) compared to the Medtronic HeartWare HVAD, with rates of 6.4% versus 16.4%, respectively.

The increased risk of NAEs with the HVAD persisted beyond the early post-implantation period, indicating that patients with this device had a 5.71 times higher hazard of experiencing major NAEs during the constant hazard phase compared to those with the HM3.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cerebrovascular Events in Patients With Centrifugal-Flow Left Ventricular Assist Devices: Propensity Score-Matched Analysis From the Intermacs Registry. Cho, SM., Mehaffey, JH., Meyers, SL., et al.[2021]

In a study of six patients who underwent a device upgrade to the HeartMate 3™ LVAD, the three-year survival rate was 100%, indicating excellent safety and efficacy of the new device.

While the HeartMate 3™ showed superior hemocompatibility and reduced pump thrombosis, there was a high risk of local re-infection in patients who exchanged their devices due to severe infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Three-year follow-up after less-invasive left ventricular assist device exchange to HeartMate 3™. Hanke, JS., Mariani, S., Merzah, AS., et al.[2022]

Left ventricular assist devices (LVADs) are crucial for providing mechanical support to patients suffering from end-stage heart failure, helping to improve their quality of life and survival rates.

As LVADs become more common, it is essential for healthcare providers to understand how these devices work, the potential complications that may arise, and effective management strategies for patients using them.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical considerations for the evaluation of patients with left ventricular assist devices. McMullen, L., Barker, K., Fried, J., et al.[2023]

In a study of 3,836 patients with continuous-flow LVADs, pre-operative health status was found to have a limited association with post-surgery outcomes, indicating that initial health conditions may not predict mortality or rehospitalization after LVAD implantation.

However, health status measured three months after surgery, particularly using the Kansas City Cardiomyopathy Questionnaire (KCCQ), was significantly associated with increased mortality risk, suggesting that ongoing health assessments post-LVAD could be crucial for patient management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of global and disease-specific health status with outcomes following continuous-flow left ventricular assist device implantation. Flint, KM., Spertus, JA., Tang, F., et al.[2018]

In a study of 734 patients implanted with continuous-flow left ventricular assist devices (LVADs), the HeartWare HVAD was associated with a significantly higher risk of stroke compared to the HeartMate II (HR: 1.8), indicating a safety concern for patients using this device.

Overall mortality rates were similar between the two devices (7.3% for HMII and 7.5% for HVAD), but the analysis revealed that while gastrointestinal bleeding and infections were comparable, the HVAD showed a concerning trend of increased stroke risk over time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events in contemporary continuous-flow left ventricular assist devices: A multi-institutional comparison shows significant differences. Stulak, JM., Davis, ME., Haglund, N., et al.[2015]

In a study of 652 patients, 74 elderly patients (aged 70 and older) received left ventricular assist devices (LVADs) as a viable treatment option for heart failure, showing that LVAD implantation can be safely performed in this age group.

Elderly patients experienced similar rates of complications and mid-term survival compared to younger patients, indicating that age alone should not be a barrier to LVAD therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Septuagenarian population has similar survival and outcomes to younger patients after left ventricular assist device implantation. Galand, V., Flécher, E., Chabanne, C., et al.[2020]

In a case series of 6 patients with left ventricular assist devices (LVADs) who underwent percutaneous coronary intervention (PCI), the procedures were performed without any acute complications, indicating a level of safety in this high-risk population.

However, the study highlighted significant risks, including fatal gastrointestinal bleeding and intractable ventricular tachycardia, particularly related to the use of combined antiplatelet and anticoagulation therapies, suggesting that while PCI can be performed, its benefits may be limited and further research is needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PCI in Patients Supported With CF-LVADs: Indications, Safety, and Outcomes. Anyanwu, EC., Ota, T., Sayer, G., et al.[2017]

Patients on the heart transplant waiting list supported by contemporary continuous-flow LVADs have significantly lower mortality rates compared to those without LVADs, particularly in urgency statuses 1A and 1B, indicating improved outcomes with modern devices.

However, complications related to LVADs can lead to a 28% rate of status upgrades, which significantly increase mortality risk, especially in patients requiring biventricular assist devices or temporary VADs, highlighting the importance of managing these complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Morbidity and mortality in heart transplant candidates supported with mechanical circulatory support: is reappraisal of the current United network for organ sharing thoracic organ allocation policy justified? Wever-Pinzon, O., Drakos, SG., Kfoury, AG., et al.[2021]

Citations

1. withpower.com withpower.com/trial/phase-heart-failure-5-2017-f9bb0

LVAD Conditioning for Heart Failure Research shows that while left ventricular assist devices (LVADs) can improve survival, they are associated with risks such as strokes and other adverse events.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12363120/

the evolving role of LVAD in reversing heart failure Multiple studies have demonstrated the potential for cardiac function recovery and subsequent weaning from mechanical assistance following the ...

3. centerwatch.com centerwatch.com/clinical-trials/listings/NCT03238690/lvad-conditioning-for-cardiac-recovery

LVAD Conditioning for Cardiac Recovery The purpose of this study is to investigate the potential recovery of heart function in end-stage heart failure patients supported with a ...

4. aging.networkofcare.org aging.networkofcare.org/sanmateo/CommunityResources/ClinicalTrials/Detail/NCT03238690?keyword=%22LVAD%22

LVAD Conditioning for Cardiac Recovery The purpose of this study is to investigate the potential recovery of heart function in end-stage heart failure patients supported with a Left Ventricular ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1934148214002159

Outcomes of Acute Inpatient Rehabilitation of Patients With ... To investigate the benefits of comprehensive inpatient rehabilitation for patients after left ventricular assist device (LVAD) implantation. Design. A ...

6. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/172239

LVAD Conditioning for Cardiac Recovery The purpose of this study is to investigate the potential recovery of heart function in end-stage heart failure patients supported with a ...

7. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/46/NCT02362646/Prot_SAP_000.pdf

Protocol Treatment of Congestive Heart Failure (REMATCH) Study Group. Long-term use of a left ventricular assist device for end-stage heart failure. N Engl J Med ...