Introducing Palliative Care (PC) Within the Treatment of End Stage Liver Disease (ESLD) (PAL-LIVER)

Introducing Palliative Care (PC) Within the Treatment of End Stage Liver Disease (ESLD): A Cluster Randomized Controlled Trial

This is a comparative effectiveness study of two pragmatic models aiming to introduce palliative care for end stage liver disease patients. The 2 comparators are:

Model 1: Consultative Palliative Care (i.e. direct access to Palliative Care provider), Model 2: Trained Hepatologist- led PC intervention (i.e. a hepatologist will receive formal training to deliver Palliative Care services)

Primary Outcome: The change in quality of life from baseline to 3 months post enrollment as assessed by FACT-Hep (Functional Assessment of Cancer Therapy- Hepatobiliary).

Primary Hypothesis: Compared to consultative PC, the trained hepatologist-led PC for ESLD patients will show superior primary outcome. In the event of nonsignificant superiority, the trained hepatologist-led PC led will show non-inferiority (NI) by ruling out a 4-point reduction (NI margin) in mean of the primary outcome as compared to the consultative PC.

Power: The study has 83.2% power to detect minimal clinically important difference (MCID) of 9 points in mean of the primary outcome between the two randomized arms. We have 79.2% power for the noninferiority hypothesis, under assumption that the trained hepatologist-led PC arm performs better than the consultative PC arm by half of the above MCID.

Setting: 19 Clinical Centers across US are recruited to participate in this study.

Qualitative nested study will interview patients, caregivers and providers to assess their experiences with participating in the palliative care trial.

Study Overview

• Status: Completed
• Conditions: End Stage Liver Disease; Decompensated Cirrhosis of Liver
• Intervention / Treatment: Other: Palliative Care

Detailed Description

This is a two armed comparative effectiveness cluster randomized controlled trial (RCT), to assess the effectiveness of two pragmatic PC models for patients with ESLD (Consultative PC vs. Trained hepatologist led PC). To prevent bias at the level of providers, randomization will take place at the level of clinical centers; however patients will be the unit of inference. There is no standard of care arm.

Embedded within this cluster-RCT is a qualitative study will be undertaken to evaluate the patient/caregiver experiences in the two PC models, using semi structured interviews.

To execute this project, we have identified 19 clinical centers to participate; 8 Veterans Health Administration (VHA) systems and 11 non-VHA, Academic Medical Centers.

Comparative Approaches:

1. Consultative PC led approach (Model 1): The PC model will include: 1) routine PC consults, using a standardized checklist , 2) in-person or telehealth visits at initial, 1, 2 and 3 months. .
2. Trained hepatologist led PC (Model 2): The Hepatologist Led PC model will comprise: 1) Hepatologist training (through E Learning modules), and 2) in person or telehealth visits utilizing the same PC checklist as utilized in Model 1. The study visits will occur at initial, 1, 2 and 3 months i.e. similar to Model 1 and follow the same visit specified agenda.

Study visits in both models could occur in-person or telehealth based, especially during in-person visit restrictions due to COVID pandemic.

Adult patients with end stage liver disease and their caregivers 18 years of age or older will be enrolled.

Primary Outcome: The change in quality of life from baseline to 3 months post enrollment as assessed by FACT-Hep (Functional Assessment of Cancer Therapy- Hepatobiliary).

Primary Hypothesis: Compared to consultative PC, the trained hepatologist-led PC for ESLD patients will show superior primary outcome. In the event of nonsignificant superiority, the trained hepatologist-led PC led will show non-inferiority (NI) by ruling out a 4-point reduction (NI margin) in mean of the primary outcome as compared to the consultative PC.

Power: The study has 83.2% power to detect clinically important difference (MCID) of 9 points in mean of the primary outcome between the two randomized arms. We have 79.2% power for the noninferiority hypothesis, under assumption that the trained hepatologist-led PC arm performs better than the consultative PC arm by half of the above MCID.

• Study Type: Interventional
• Enrollment (Actual): 1494
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama
  • Arizona
    • Phoenix, Arizona, United States, 85006
      • Banner Health- University Medical Center
  • California
    • Fresno, California, United States, 93701
      • UCSF Fresno
    • Loma Linda, California, United States, 92354
      • Loma Linda Unversity Health
  • Connecticut
    • West Haven, Connecticut, United States, 06516
      • VA West Haven
  • Florida
    • Gainesville, Florida, United States, 32611
      • University of Florida
    • Miami, Florida, United States, 33125
      • Miami VA Medical Center
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University
  • Massachusetts
    • Boston, Massachusetts, United States, 02130
      • VA Boston
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Medical Center
  • Missouri
    • Kansas City, Missouri, United States, 64128
      • Kansas City VA Medical Center
  • New York
    • Brooklyn, New York, United States, 11209
      • VA New York Harbor
    • The Bronx, New York, United States, 10468
      • VA Bronx
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • UNC Liver Center
    • Durham, North Carolina, United States, 27705
      • Durham V.A. Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19141
      • Albert Einstein Medical Center
    • Philadelphia, Pennsylvania, United States, 19104
      • Corporal Michael J. Crescenz VA Medical Center
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 120 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Eligible patients were adults (≥18 years) with:

1. cirrhosis and a decompensation event indicative of ESLD (such as ascites, variceal bleeding or hepatic encephalopathy) within the prior 6 months, or
2. hepatocellular cancer (HCC) except Barcelona Stage D, or multifocal HCC (as defined by standard guidelines and confirmed by treating hepatologist).

Additional inclusion criteria included English literacy and the capacity to complete study assessments.

Exclusion criteria were hepatologist assessed life expectancy <6 months, prior liver transplantation, anticipated liver transplantation within 3 months, inability to consent, or receipt of PC within the previous three months.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Model 1: Consultative Palliative Care; Direct access to Palliative Care provider, who will offer palliative care to patients and caregivers, as guided by a standard PC (palliative care) checklist.	Other: Palliative Care; The intervention will comprise an approach to render palliative care, as taught to hepatologists through an on-line learning platform, and as delivered by PC providers as routine care. The elements of the intervention, which will be guided by a checklist and implemented over the course of interactions with the patient and caregivers at the initial, 1, 2, and 3 month visits, to include: Patient/caregiver understanding of diagnosis, illness and prognosis; Symptom assessment and management; Psychosocial assessment and management; Distress screening and management; Discussion of goals of care; Advanced directives
Active Comparator: Model 2: Trained Hepatologist- led PC; 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	Other: Palliative Care; The intervention will comprise an approach to render palliative care, as taught to hepatologists through an on-line learning platform, and as delivered by PC providers as routine care. The elements of the intervention, which will be guided by a checklist and implemented over the course of interactions with the patient and caregivers at the initial, 1, 2, and 3 month visits, to include: Patient/caregiver understanding of diagnosis, illness and prognosis; Symptom assessment and management; Psychosocial assessment and management; Distress screening and management; Discussion of goals of care; Advanced directives

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality of Life (QOL)	FACT-Hep (Functional Assessment of Cancer Therapy- Hepatobiliary) will be used to assess QOL. This is a 45 item self-reported instrument. FACT-Hep total score is the primary outcome. The scores range from 0 to 180. Higher scores reflect better QOL. This measure is for patients only.	Mean change in FACT-Hep total score from baseline to 3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient's Symptom Burden	Modified Edmonton Symptom Assessment Scale (ESAS) evaluated 13 symptoms (tiredness, nausea, depression, anxiety, drowsiness, appetite, well-being, shortness of breath, muscle cramps, sexual function, sleep, itch, pain) on a 10-point scale, where 0 is no symptom and 10 is the maximum severity of symptom. The total score ranges from 0-130. Higher scores reflect higher symptom burden. This measure is for patients only.	Change in ESAS total score from baseline to 3 months
Patient's Depression Severity	PHQ-9 (Personal Health Questionnaire) is one of the very commonly used tools to assess severity of depression in different settings, and has 9 questions. Each question is rated on a 4 point scale, with total score ranging from 0 to 27. Higher scores reflects greater severity of depression. Scores from 0-4 equates to no depression, 5-9 mild, 10-14 moderate, 15-19 mod severe and >20 reflects severe depression. This measure is for patients only.	Change in PHQ-9 scores from baseline to 3 months
Patient Satisfaction	FAMCARE-P13 (Family Satisfaction with Cancer Care- Patient scale) is a brief validated instrument used to assess patient satisfaction with outpatient palliative care interventions. It consists of 13 questions, with Likert scale response options. Higher scores imply better satisfaction from the care received. This measure is for patients only.	Change in FAMCARE-P scores from baseline to 3 months.
Caregiver Burden (Completed by the Caregivers of Patients Who Were Enrolled as a Dyad). Caregivers Were Consented Separately.	Zarit Burden Interview-12 (ZBI-12) a short, validated instrument is extensively used for palliative care research in diverse populations. It has high internal consistency, reliability and convergent validity to assess caregiver burden. Higher score reflects higher caregiver burden. The score ranges from 0- 48. This measure is for caregivers only.	Change in ZBI-12 scores from baseline to 3 months
Distress	Distress thermometer (DT) ranks level of distress from 0- 10, Higher scores reflect higher distress. This is for patients only.	Change in Distress from baseline to 3 months
Goal Concordant Care Questionnaire/ GCC (Patients)	There are two subscales which assess Goal Concordant Care (GCC): Goals of Care Conversations (GoC) (7 items scale), assessing the perceived extent to which providers have engaged the patient in the process of advance care planning (score range 0-10) and; Care Concordant with Preferences (CCP) (4 items scale), measuring the perceived alignment of delivered care with patient preferences (score range 0-2). Higher values represent a better outcome. There is no total score for this measure, only subscale scores apply.	Change in GCC scales from baseline to 3 months
Caregiver Quality of Life	PROMIS- 29 (Patient Reported Outcomes Measurement Information System) assess overall quality of life and is summarized as : Physical and Mental health summary scores. Range 0-100 for both. Higher scores reflect higher physical function but worse mental health (as higher scores reflect higher domain assessed). Here we report for caregivers only.	Change in caregiver QoL from baseline to 3 months
Goal Concordant Care/ GCC (Caregivers)	There are two subscales which assess Goal Concordant Care (GCC): Goals of Care Conversations (GoC) (7 items scale), assessing the perceived extent to which providers have engaged the patient in the process of advance care planning (score range 0-10) and; Care Concordant with Preferences (CCP) (4 items scale), measuring the perceived alignment of delivered care with patient preferences (score range 0-2). Higher values represent a better outcome. There is no total score for this measure, only subscale scores apply. Here we report for caregivers.	Change in GCC from baseline to 3 months
Mortality Over 12 Months.	Number of Patients that Died from Baseline to 12 Month.	Survival over 12 months

Collaborators and Investigators

• Sponsor: Albert Einstein Healthcare Network
• Collaborators: Patient-Centered Outcomes Research Institute
• Investigators: Principal Investigator: Manisha Verma, MD, MPH, Albert Einstein Healthcare Network; Principal Investigator: Victor Navarro, MD, Albert Einstein Healthcare Network

Publications and helpful links

General Publications

• DeNofrio JC, Verma M, Kosinski AS, Navarro V, Taddei TH, Volk ML, Bakitas M, Ramchandran K. Palliative Care Always: Hepatology-Virtual Primary Palliative Care Training for Hepatologists. Hepatol Commun. 2022 Apr;6(4):920-930. doi: 10.1002/hep4.1849. Epub 2021 Oct 31.
• Verma M, Tapper EB, Singal AG, Navarro V. Nonhospice Palliative Care Within the Treatment of End-Stage Liver Disease. Hepatology. 2020 Jun;71(6):2149-2159. doi: 10.1002/hep.31226.
• Verma M, Bakitas MA. Creating Effective Models for Delivering Palliative Care in Advanced Liver Disease. Curr Hepatol Rep. 2021;20(2):43-52. doi: 10.1007/s11901-021-00562-0. Epub 2021 Apr 10.
• Hoppmann N, Bakitas M, Stockdill M, DeNofrio J, Navarro V, Verma M. Palliative Care for Advanced Liver Disease: Hepatology and Palliative Care Specialists Experiences. J Pain Symptom Manage. 2025 Oct 8:S0885-3924(25)00871-1. doi: 10.1016/j.jpainsymman.2025.09.028. Online ahead of print.
• Verma M, Kosinski AS, Volk ML, Taddei T, Ramchandran K, Bakitas M, Green K, Green L, Navarro V. Introducing Palliative Care within the Treatment of End-Stage Liver Disease: The Study Protocol of a Cluster Randomized Controlled Trial. J Palliat Med. 2019 Sep;22(S1):34-43. doi: 10.1089/jpm.2019.0121.

Helpful Links

• PCORI web release

Study record dates

Study Major Dates

• Study Start (Actual): January 30, 2019
• Primary Completion (Actual): June 30, 2025
• Study Completion (Actual): August 30, 2025

Study Registration Dates

• First Submitted: May 17, 2018
• First Submitted That Met QC Criteria: May 17, 2018
• First Posted (Actual): May 30, 2018

Study Record Updates

• Last Update Posted (Estimated): December 2, 2025
• Last Update Submitted That Met QC Criteria: November 18, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: palliative care; hepatology; decompensated cirrhosis
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Liver Failure; Hepatic Insufficiency; End Stage Liver Disease; Therapeutics; Patient Care; Health Services; Health Care Facilities Workforce and Services; Palliative Care
• Other Study ID Numbers: Pro00092149

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No