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End Stage Liver DiseasePAL-LIVERNCT03540771

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

A study testing Palliative Care in people with End Stage Liver Disease and Decompensated Cirrhosis of Liver, run by Albert Einstein Healthcare Network at 19 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 to 120 years
What is being tested?
Palliative Care
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1,494 participants
Where
19 sitesUnited States
Study dates
30 Jan 2019to 30 Aug 2025
Phase
Interventional
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 to 120 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Eligible patients were adults (≥18 years) with:
  • cirrhosis and a decompensation event indicative of ESLD (such as ascites, variceal bleeding or hepatic encephalopathy) within the prior 6 months, or
  • 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.

Who cannot join

None listed.

Trial locations and contacts

19 sites in 1 country.

19 sites in 1 country

United States19 sites

  • University of Michigan Medical Center

    Ann Arbor, Michigan, 48109

  • University of Alabama

    Birmingham, Alabama, 35233

  • VA Boston

    Boston, Massachusetts, 02130

  • VA New York Harbor

    Brooklyn, New York, 11209

  • UNC Liver Center

    Chapel Hill, North Carolina, 27599

  • Medical University of South Carolina

    Charleston, South Carolina, 29425

  • Durham V.A. Medical Center

    Durham, North Carolina, 27705

  • UCSF Fresno

    Fresno, California, 93701

  • University of Florida

    Gainesville, Florida, 32611

  • Baylor College of Medicine

    Houston, Texas, 77030

  • Indiana University

    Indianapolis, Indiana, 46202

  • Kansas City VA Medical Center

    Kansas City, Missouri, 64128

  • Loma Linda Unversity Health

    Loma Linda, California, 92354

  • Miami VA Medical Center

    Miami, Florida, 33125

  • Corporal Michael J. Crescenz VA Medical Center

    Philadelphia, Pennsylvania, 19104

  • Albert Einstein Medical Center

    Philadelphia, Pennsylvania, 19141

  • Banner Health- University Medical Center

    Phoenix, Arizona, 85006

  • VA Bronx

    The Bronx, New York, 10468

  • VA West Haven

    West Haven, Connecticut, 06516

Other trials in United States

About this study

Official title: 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)

Read more

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.

Read the 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.

Being tested
Palliative Care
Keywords
palliative care, hepatology, decompensated cirrhosis
Medical subject headings
End Stage Liver Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Palliative CareOther

    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:

    1. Patient/caregiver understanding of diagnosis, illness and prognosis
    2. Symptom assessment and management
    3. Psychosocial assessment and management
    4. Distress screening and management
    5. Discussion of goals of care
    6. Advanced directives
Study groups in NCT03540771
Study groupRoleWhat they receive
Model 1: Consultative Palliative CareActive comparatorDirect access to Palliative Care provider, who will offer palliative care to patients and caregivers, as guided by a standard PC (palliative care) checklist.
Receives: Other: Palliative Care
Model 2: Trained Hepatologist- led PCActive comparatorA 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
Receives: Other: Palliative Care

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Mean change in FACT-Hep total score from baseline to 3 months

Secondary outcomes (9)

  1. 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.

    Measured: Change in ESAS total score from baseline to 3 months

  2. 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.

    Measured: Change in PHQ-9 scores from baseline to 3 months

  3. 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.

    Measured: Change in FAMCARE-P scores from baseline to 3 months.

  4. Distress

    Distress thermometer (DT) ranks level of distress from 0- 10, Higher scores reflect higher distress.

    This is for patients only.

    Measured: Change in Distress from baseline to 3 months

  5. Goal Concordant Care Questionnaire/ GCC (Patients)

    There are two subscales which assess Goal Concordant Care (GCC):

    1. 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
    2. 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.

    Measured: Change in GCC scales from baseline to 3 months

  6. 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.

    Measured: Change in ZBI-12 scores from baseline to 3 months

  7. 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.

    Measured: Change in caregiver QoL from baseline to 3 months

  8. Goal Concordant Care/ GCC (Caregivers)

    There are two subscales which assess Goal Concordant Care (GCC):

    1. 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
    2. 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.

    Measured: Change in GCC from baseline to 3 months

  9. Mortality Over 12 Months.

    Number of Patients that Died from Baseline to 12 Month.

    Measured: Survival over 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 May 2018
  2. Study start30 Jan 2019
  3. Primary completion30 Jun 2025
  4. Study completion30 Aug 2025

Resources

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 N/A
Primary purpose
Supportive care
Allocation
Randomised
Intervention model
Parallel groups
Model description
Model 1: Consultative Palliative Care (i.e. direct access to Palliative Care provider), versus Model 2: Trained Hepatologist- led PC intervention (i.e. a hepatologist will receive formal training to deliver Palliative Care services)
Masking
None (open label)
Enrolment
1,494 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03540771
Sponsor's protocol ID
Pro00092149
Acronym
PAL-LIVER
Status last verified
Nov 2025
First submitted
17 May 2018
Last updated
2 Dec 2025
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 32167615

  • 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.

    PubMed 34719137

  • 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.

    PubMed 33868897

  • Verma M, Navarro V, Kosinski A, Taddei T, Kalman R, Barritt Iv AS, Jakab S, Serper M, Orman E, Balakrishnan M, Rakoski M, Rockey D, Hunt K, Cabrera R, Aytaman A, John B, Baffy G, Nathan R, Tapper E, Roytman M, McGuire B, Hoppmann N, Woodrell C, Bakitas M, Yue Y, Reeve B, Lin L, Tantala R, Volk M. Palliative Care Intervention for Patients With End-Stage Liver Disease: A Cluster Randomized Clinical Trial. JAMA Intern Med. 2026 Jun 1;186(6):677-686. doi: 10.1001/jamainternmed.2026.0571.

    PubMed 41973444

  • 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. 2026 Jan;71(1):157-167. doi: 10.1016/j.jpainsymman.2025.09.028. Epub 2025 Oct 8.

    PubMed 41072740

  • 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.

    PubMed 31486722

Questions about this trial

What is this clinical trial studying?

A study testing Palliative Care in people with End Stage Liver Disease and Decompensated Cirrhosis of Liver, run by Albert Einstein Healthcare Network at 19 sites 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 5 inclusion and 0 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: finished, as of the sponsor's last update on 2 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 19 sites 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 27 Oct 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Quality of Life (QOL) (time frame: Mean change in FACT-Hep total score from baseline to 3 months). 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 NCT03540771, which also lists 6 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 2 Dec 2025.

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