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

NCT ID: NCT03540771

Last Updated: 2025-12-02

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

1494 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-01-30

Study Completion Date

2025-08-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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End Stage Liver Disease Decompensated Cirrhosis of Liver

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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)
Primary Study Purpose

SUPPORTIVE_CARE

Blinding Strategy

NONE

The study investigators were masked to comparative outcomes measures until the study was completed and database was locked.

Study Groups

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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.

Group Type ACTIVE_COMPARATOR

Palliative Care

Intervention Type OTHER

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

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

Group Type ACTIVE_COMPARATOR

Palliative Care

Intervention Type OTHER

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

Interventions

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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:

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

Intervention Type OTHER

Eligibility Criteria

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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).
Minimum Eligible Age

18 Years

Maximum Eligible Age

120 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Patient-Centered Outcomes Research Institute

OTHER

Sponsor Role collaborator

Albert Einstein Healthcare Network

OTHER

Sponsor Role lead

Responsible Party

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Manisha Verma

Director, Research, Department of Medicine

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Manisha Verma, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

Albert Einstein Healthcare Network

Victor Navarro, MD

Role: PRINCIPAL_INVESTIGATOR

Albert Einstein Healthcare Network

Locations

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University of Alabama

Birmingham, Alabama, United States

Site Status

Banner Health- University Medical Center

Phoenix, Arizona, United States

Site Status

UCSF Fresno

Fresno, California, United States

Site Status

Loma Linda Unversity Health

Loma Linda, California, United States

Site Status

VA West Haven

West Haven, Connecticut, United States

Site Status

University of Florida

Gainesville, Florida, United States

Site Status

Miami VA Medical Center

Miami, Florida, United States

Site Status

Indiana University

Indianapolis, Indiana, United States

Site Status

VA Boston

Boston, Massachusetts, United States

Site Status

University of Michigan Medical Center

Ann Arbor, Michigan, United States

Site Status

Kansas City VA Medical Center

Kansas City, Missouri, United States

Site Status

VA New York Harbor

Brooklyn, New York, United States

Site Status

VA Bronx

The Bronx, New York, United States

Site Status

UNC Liver Center

Chapel Hill, North Carolina, United States

Site Status

Durham V.A. Medical Center

Durham, North Carolina, United States

Site Status

Corporal Michael J. Crescenz VA Medical Center

Philadelphia, Pennsylvania, United States

Site Status

Albert Einstein Medical Center

Philadelphia, Pennsylvania, United States

Site Status

Medical University of South Carolina

Charleston, South Carolina, United States

Site Status

Baylor College of Medicine

Houston, Texas, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 32167615 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 34719137 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 33868897 (View on PubMed)

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.

Reference Type DERIVED
PMID: 41072740 (View on PubMed)

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.

Reference Type DERIVED
PMID: 31486722 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan: Study Protocol with detailed outcomes and procedures

View Document

Document Type: Statistical Analysis Plan: Detailed Statistical Analysis Plan

View Document

Related Links

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Other Identifiers

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Pro00092149

Identifier Type: -

Identifier Source: org_study_id

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