Palliative Care for End Stage Liver Disease

(PAL-LIVER Trial)

No longer recruiting at 19 trial locations

Overseen By Manisha Verma, MBBS, MPH

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Albert Einstein Healthcare Network

Disqualifiers: MELD> 30, Life expectancy < 6 months

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: 4

Duration: 3 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two methods of providing palliative care to individuals with end-stage liver disease. One method offers patients direct access to a palliative care expert, while the other involves a liver specialist trained in palliative care. The trial aims to determine which method more effectively improves quality of life over three months. Individuals with end-stage liver disease and complications, such as liver cancer, may qualify if they have a caregiver willing to participate. As an unphased trial, this study provides a unique opportunity to contribute to research that could enhance future palliative care options.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that these palliative care models are safe for end stage liver disease patients?

Research has shown that palliative care is generally well-tolerated by people with end-stage liver disease (ESLD). Studies have found that it can improve quality of life and help manage symptoms for these patients.

In the consultative palliative care model, direct access to palliative care providers can increase patient comfort and reduce emergency room visits. Patients have reported better symptom control and greater satisfaction with their care.

In the trained hepatologist-led palliative care model, early findings suggest this approach is also safe. Hepatologists with special training in palliative care have effectively supported patients, improving their quality of life.

Both models aim to enhance patient comfort and overall well-being. Research has not identified any significant harmful effects linked to these palliative care methods. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the palliative care approaches for end-stage liver disease being studied because they aim to improve the quality of life for patients by offering personalized and accessible support. Unlike the standard care options, which primarily focus on medical management of symptoms, these models introduce direct palliative care either through a specialized provider or a specially trained hepatologist. This could enhance holistic care by addressing not just physical symptoms, but also emotional and psychological needs, potentially providing more comprehensive support for both patients and their caregivers.

What evidence suggests that this trial's palliative care models could be effective for end stage liver disease?

Research has shown that palliative care can greatly improve the quality of life for people with end-stage liver disease (ESLD). In this trial, participants will be assigned to one of two models of palliative care. Model 1 involves direct access to a palliative care specialist, which studies have found leads to better symptom management and overall well-being. Model 2 involves liver specialists who receive extra training to provide palliative care, a method also expected to enhance quality of life. Both approaches focus on meeting the physical and emotional needs of ESLD patients, providing them with relief and support. ^{2 6 7 8 9}

Who Is on the Research Team?

Victor Navarro, MD

Principal Investigator

Albert Einstein Healthcare Network

Manisha Verma, MD, MPH

Principal Investigator

Albert Einstein Healthcare Network

Are You a Good Fit for This Trial?

This trial is for patients with new or ongoing complications of End Stage Liver Disease, including liver cancer, regardless of their transplant status. They must have a caregiver willing to participate. It's not for those with a MELD score over 30 or an expected life expectancy under 6 months.

Inclusion Criteria

I have advanced liver disease or liver cancer and have a caregiver willing to participate.

Exclusion Criteria

Your liver disease is so severe (MELD score > 30) that you may not live more than 6 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive palliative care through either a consultative model or a trained hepatologist-led model, with in-person visits at initial, 1, 2, and 3 months

3 months

4 visits (in-person)

Follow-up

Participants are monitored for changes in quality of life, patient satisfaction, symptom burden, depression severity, and caregiver burden

3 months

What Are the Treatments Tested in This Trial?

Interventions

• Palliative Care

Trial Overview The study compares two ways to provide palliative care: one where patients see a specialist and another where liver doctors are trained in palliative care. The main goal is to see how these approaches affect quality of life after three months using the FACT-Hep scale.

How Is the Trial Designed?

Group I: Model 1: Consultative Palliative Care Active Control 1 Intervention

Direct access to Palliative Care provider, who will offer palliative care to patients and caregivers, as guided by a standard PC (palliative care) checklist.

Group II: Model 2: Trained Hepatologist- led PC Active Control 1 Intervention

A hepatologist will receive formal training to deliver Palliative Care (PC) services, and will offer palliative care to patients and caregivers following the same PC checklist as in Model 1

Palliative Care is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Palliative Care for:

• Symptom management for various conditions including cancer, neurological disorders, and end-of-life care

Approved in United States as Palliative Care for:

• Symptom management for various conditions including cancer, neurological disorders, and end-of-life care

Approved in Canada as Palliative Care for:

• Symptom management for various conditions including cancer, neurological disorders, and end-of-life care

Who Is Running the Clinical Trial?

Albert Einstein Healthcare Network

Lead Sponsor

Trials

65

Recruited

869,000+

Patient-Centered Outcomes Research Institute

Collaborator

Trials

592

Recruited

27,110,000+

Published Research Related to This Trial

Early integration of palliative care in patients with end-stage liver disease (ESLD) can significantly improve quality of life, reduce anxiety, and enhance satisfaction with care for both patients and caregivers, as supported by recent literature.

Despite its benefits, palliative care is still underutilized in liver disease, highlighting the need for better education among healthcare providers and the development of guidelines to promote its acceptance and implementation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Palliative care and end-stage liver disease: a critical review of current knowledge. Rakoski, MO., Volk, ML.[2020]

Specialist palliative care can significantly improve symptoms and facilitate advance care planning for patients on liver transplant waiting lists, but these patients often receive limited palliative care support.

Healthcare professionals, particularly liver physicians, are hesitant to refer patients to palliative care due to concerns about the perceived curative nature of liver transplants and a lack of clarity on referral criteria.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Palliative Care for Patients with End-Stage Liver Disease on the Liver Transplant Waiting List: An International Systematic Review. Vijeratnam, SS., Candy, B., Craig, R., et al.[2022]

Patients with advanced liver disease experience significant symptom burden and have considerable palliative care needs, highlighting the importance of improving their quality of life.

There is a global variability in the involvement of palliative care for these patients, indicating a need for further research and development of new care models to enhance access to specialist palliative services.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emerging Role of Palliative Care in Patients with Advanced Liver Disease. Jordan, RI., Tandon, P.[2021]

The Supportive and Palliative Care Indicator Tool (SPICT) demonstrated excellent performance in identifying liver patients who may need specialist palliative care, with a sensitivity of 93% and a positive predictive value of 93% based on a review of 117 medical notes.

The Bristol Prognostic Screening Tool (BPST) also showed good performance for identifying palliative care needs, but both tools had only moderate ability to predict 12-month mortality, indicating they are more effective for referral purposes than for mortality prediction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Do screening tools assess palliative care needs and 12-month mortality in patients admitted to hepatology in-patient wards? Low, J., Carroll, C., Wilson, J., et al.[2022]

The rising mortality rate from chronic liver disease in the UK highlights the urgent need for improved palliative care, as patients experience significant symptoms comparable to other life-limiting illnesses.

Effective palliative care should be integrated with active disease management by the hepatology team, ensuring that discussions about disease progression and advance care planning occur alongside treatment, while also addressing the social and psychological challenges faced by patients and their families.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Palliative care in liver disease: what does good look like? Woodland, H., Hudson, B., Forbes, K., et al.[2023]

In a study of 44,933 hospitalized patients, those with liver disease were younger and had a higher in-hospital mortality rate (28%) compared to cancer patients (16.8%), highlighting the severity of liver disease in hospital settings.

Patients with liver disease were more likely to receive palliative care consultations focused on goals of care (81.7%) rather than pain management (10.9%), yet both groups showed similar improvements in symptoms and changes in resuscitation preferences after consultations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes of Palliative Care Consultations for Hospitalized Patients With Liver Disease. Ufere, NN., O'Riordan, DL., Bischoff, KE., et al.[2020]

Palliative care services are often underutilized in managing patients with decompensated cirrhosis and end-stage liver disease (ESLD), which can negatively impact their quality of life.

Integrating palliative care into the treatment of ESLD can enhance symptom management and provide essential support for patients and caregivers, highlighting the need for greater awareness and recognition of its benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Palliative care in end-stage liver disease: Time to do better? Mazzarelli, C., Prentice, WM., Heneghan, MA., et al.[2019]

Palliative care is increasingly recognized as essential for patients with decompensated cirrhosis, particularly during advanced and terminal stages, yet it is often overlooked by hepatologists and liver transplant teams.

Recent guidance emphasizes a collaborative and standardized approach to palliative care, focusing on symptom management and end-of-life issues, which should be adopted by all healthcare workers involved in the care of cirrhotic patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Palliative care in cirrhotic patients: Brief summary of recent AASLD guidance. Ozdogan, OC.[2022]

In a feasibility trial involving 36 patients with end-stage liver disease, long-term abdominal drains showed lower hospital resource utilization and costs compared to large-volume paracentesis, suggesting they may be a more efficient option for managing refractory ascites.

While complications like cellulitis and leakage were more common in the long-term drain group (41% vs. 11% in the paracentesis group), the overall safety profile and high questionnaire completion rates indicate that patients found long-term drains acceptable and potentially transformative for their care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomised clinical trial: palliative long-term abdominal drains vs large-volume paracentesis in refractory ascites due to cirrhosis. Macken, L., Bremner, S., Gage, H., et al.[2021]

Patients evaluated for liver transplantation who received palliative care (PC) were generally younger and had more severe liver disease, as indicated by higher MELD scores and rates of hepatic encephalopathy, compared to those who did not receive PC.

Utilization of PC services was associated with improved end-of-life outcomes, including a significantly lower likelihood of dying in the ICU and a higher likelihood of having advance care planning discussions and family meetings, indicating better quality of care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Palliative Care and End-of-Life Outcomes in Patients Considered for Liver Transplantation: A Single-Center Experience in the US Midwest. Kieffer, SF., Tanaka, T., Ogilvie, AC., et al.[2023]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40521696/

Effectiveness of palliative care in the management of end- ... The aim of this systematic review is to evaluate the effectiveness of palliative care in treating adults with end-stage liver disease (ESLD)

2. pcori.org pcori.org/research-results/2017/comparing-two-ways-offer-palliative-care-improve-quality-life-adults-end-stage-liver-disease

Comparing Two Ways To Offer Palliative Care To Improve ... This study compares quality of life outcomes for adults with end stage liver disease (ESLD), and their caregivers, who receive palliative ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12530434/

Examining the implementation of home-based palliative ... Despite robust evidence of the value of home palliative care in other advanced diseases, this has not been well studied in patients with ESLD.

4. mdpi.com mdpi.com/2673-4389/5/3/39

Palliative Care in End-Stage Liver Disease Multiple studies have demonstrated that palliative care improves symptom control and enhances quality of life in ESLD patients [38,73,74]. The pioneering study ...

5. journals.lww.com journals.lww.com/hep/fulltext/9900/developing_palliative_care_interventions_in_liver.1245.aspx

Developing palliative care interventions in liver disease... We describe the completed qualitative summative evaluation study, embedded within PALliative Care for end stage LIVER diseases, an in-progress ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10025682/

Palliative Care for Patients with End-Stage Liver Disease In a seminal study, patients were removed from the transplant wait list due to noncompliance or substance abuse in 26% and progressive organ ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05238779

An Integrative Model for Palliative Care in End-Stage Liver ... The purpose of this research study is to understand the impact of palliative care in ESLD on quality of life, emergency room or hospital visits, and on care ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S0885392425008711

Palliative Care for Advanced Liver Disease: Hepatology ... PAL-liative Care for end stage LIVER diseases (PAL-LIVER) was a 19-site cluster, randomized comparative effectiveness trial compared primary PC ...

9. journals.sagepub.com journals.sagepub.com/doi/10.1177/08258597241296116

Palliative Homecare in Chronic Liver Disease: A Cohort ... In end-stage liver disease (ESLD), the survival of patients is approximately 2 years. Despite the poor prognosis and high symptom burden, ...