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).

14 Clinical Centers across US are recruited to participate in this study.

Study Overview

• Status: Recruiting
• Conditions: End Stage Liver Disease
• Intervention / Treatment: Other: Palliative Care

Detailed Description

This is a two armed multicenter 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. Parallel to this cluster-RCT, 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 14 clinical centers to participate; 7 Veterans Health Administration (VHA) systems and 7 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 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 visits utilizing the same PC checklist as utilized in Model 1. The in-person visits will occur at initial, 1, 2 and 3 months i.e. similar to Model 1 and follow the same visit specified agenda.

Adult patients 18 years of age or older will be enrolled. With 14 clinical centers in different geographic locations and diversity in race/ ethnicity, 1260 patient/ caregiver dyads will be enrolled.

• Study Type: Interventional
• Enrollment (Anticipated): 1260
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Manisha Verma, MBBS, MPH; Phone Number: 2154561026; Email: VermaM@einstein.edu

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • Recruiting
      • University of Alabama
      • Contact: Brendan McGuire, MD
  • Arizona
    • Phoenix, Arizona, United States, 85006
      • Recruiting
      • Banner Health- University Medical Center
      • Contact: Rohit Nathan, DO
  • California
    • Fresno, California, United States, 93701
      • Recruiting
      • UCSF Fresno
      • Contact: Marina Roytman, MD
    • Loma Linda, California, United States, 92354
      • Recruiting
      • Loma Linda Unversity Health
      • Contact: Mina Rakoski, MD
  • Connecticut
    • West Haven, Connecticut, United States, 06516
      • Recruiting
      • VA West Haven
      • Contact: Simona Jakab, MD
  • Florida
    • Gainesville, Florida, United States, 32611
      • Recruiting
      • University of Florida
      • Contact: Roniel Cabrera, MD
    • Miami, Florida, United States, 33125
      • Recruiting
      • Miami VA Medical Center
      • Contact: Binu John, MD
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Recruiting
      • Indiana University
      • Contact: Eric Orman, MD
  • Massachusetts
    • Boston, Massachusetts, United States, 02130
      • Recruiting
      • VA Boston
      • Contact: Gyorgy Baffy, MD
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Recruiting
      • University of Michigan Medical Center
      • Contact: Elliott Tapper, MD
  • Missouri
    • Kansas City, Missouri, United States, 64128
      • Recruiting
      • Kansas City VA Medical Center
      • Contact: Prashant Pandya, MD
  • New York
    • Bronx, New York, United States, 10468
      • Recruiting
      • VA Bronx
      • Contact: Kristel Hunt, MD
    • Brooklyn, New York, United States, 11209
      • Recruiting
      • VA New York Harbor
      • Contact: Ayse Ayatman, MD
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • Recruiting
      • UNC Liver Center
      • Contact: Sidney Baritt, MD
    • Durham, North Carolina, United States, 27705
      • Completed
      • Durham V.A. Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • Corporal Michael J. Crescenz VA Medical Center
      • Contact: Marina Serper, MD
    • Philadelphia, Pennsylvania, United States, 19141
      • Recruiting
      • Albert Einstein Medical Center
      • Contact: Richard Kalman, MD
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Recruiting
      • Medical University of South Carolina
      • Contact: Donald Rockey, MD
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • Baylor College of Medicine
      • Contact: Maya Balakrishnan, MD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

Patients with new onset or ongoing complications of End Stage Liver Disease including Hepatocellular Cancer (HCC) (irrespective of their transplant status), with a caregiver willing to participate.

Exclusion Criteria:

MELD> 30 or Expected life expectancy of less than 6 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. The scores range from 0 to 160. Higher scores reflect better QOL.	Change in QOL from baseline to 3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient's symptom burden	Edmonton Symptom Assessment Scale (ESAS) will evaluate 11 symptoms (pain, fatigue, myalgia, sexual dysfunction, anxiety, sleep disturbance, appetite, well-being, dyspnea, pruritus and ability to think clearly) on a 10-point scale, where 0 is no symptom and 10 is the maximum severity of symptom.	Change in ESAS scores 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.	Change in PHQ-9 scores from baseline to 3 months
Caregiver burden	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. It has high correlation [Rho (95% CI) 0.95 (0.92- 0.96)] with the long form, and is less burdensome. The sensitivity and specificity is 92% and 94% with a cutoff score of 12.	Change in ZBI-12 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 measures the availability of care, symptom management, psychosocial care and information sharing including support for decision making. It consists of 13 questions, with Likert scale response options with high reliability. Higher scores imply better satisfaction from the care received.	Change in FAMCARE-P scores from baseline to 3 months.

Collaborators and Investigators

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

Publications and helpful links

General Publications

• 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.
• 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. Review.
• 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, 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. Review.

Helpful Links

• PCORI web release
• Study Protocol

Study record dates

Study Major Dates

• Study Start (Actual): January 30, 2019
• Primary Completion (Anticipated): July 31, 2024
• Study Completion (Anticipated): May 31, 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 (Actual): April 13, 2022
• Last Update Submitted That Met QC Criteria: April 5, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: palliative care; hepatology
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Failure; Hepatic Insufficiency; Liver Diseases; End Stage Liver Disease
• 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