LiverPAL: A Trial of Inpatient Palliative Care for Patients With Advanced Liver Disease (LiverPAL)

LiverPAL: A Randomized Trial of Inpatient Palliative Care for Patients With Advanced Liver Disease

The goal of this clinical trial is to evaluate whether early integration of palliative care in the care of hospitalized patients with advanced liver disease (AdvLD) can improve patients' quality of life, physical symptoms, mood, and serious illness communication. Palliative care is a medical specialty focused on lessening (or "palliating") symptoms and assisting in coping with serious illness.

Study Overview

• Status: Recruiting
• Conditions: Cirrhosis; Cirrhosis, Liver; End Stage Liver DIsease; Liver Disease Chronic; Advanced Cirrhosis
• Intervention / Treatment: Behavioral: LiverPAL

Detailed Description

The main purpose of this study is to compare two types of care - usual hepatology care and usual hepatology care with early involvement of palliative care clinicians to see which is better for improving the experience of hospitalized patients with advanced liver disease (AdvLD).

The investigators aim to find out whether introducing hospitalized patients with AdvLD to the palliative care team that specializes in symptom management can improve the quality of life and physical and psychological symptoms that patients and families experience during their hospitalizations as well as enhance the quality of patients' end of life care.

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Lucinda Li, BS; Phone Number: 617-726-3670; Email: luli1@mgh.harvard.edu
• Study Contact Backup: Name: Ennie Zhu, AB; Phone Number: 617-724-1316; Email: ezhu3@mgh.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts General Hospital
      • Contact: Lucinda Li, BS; Phone Number: 617-726-3670; Email: luli@mgh.harvard.edu
      • Contact: Enya Zhu, BA; Phone Number: 617-724-1316; Email: ezhu3@mgh.harvard.edu
      • Principal Investigator: Nneka Ufere, MD MSCE

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Patient Inclusion Criteria:

1. Hospitalized patient with a diagnosis of advanced liver disease, defined as cirrhosis with one of the following (new or ongoing) within the prior six months from date of consent:

   • Ascites (requiring diuretics or serial large volume paracenteses)
   • Spontaneous bacterial peritonitis
   • Hepatic hydrothorax (requiring diuretics)
   • Variceal bleed (with one or more occurrences)
   • Overt hepatic encephalopathy (requiring medications)
2. Ability to comprehend English

Patient Exclusion Criteria:

1. Prior history of liver transplantation
2. Have uncontrolled hepatic encephalopathy, cognitive impairment, psychiatric disorder or other comorbid condition which the primary medical, hepatology, and/or transplant surgery teams believes prohibits the ability to provide informed consent
3. Current or recent (within 5 years of receiving curative cancer treatment) history of extrahepatic malignancy (excluding non-melanoma skin cancer)
4. Presence of hepatocellular carcinoma beyond Milan criteria
5. Are already receiving hospice care
6. Receive a score of <10 on the Simplified Animal Naming Test

Caregiver Inclusion Criteria

1. Adult caregiver (≥ 18 years of age)
2. A relative or friend identified by the patient upon whom the patient relies for help and who likely is to be present in-person during hospitalizations or clinic appointments, or willing to participate by phone
3. Ability to comprehend English and can complete questionnaires

Caregiver Exclusion Criteria

1. Inability to comprehend English

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Usual Hepatology Care; Usual hepatology care
Experimental: Usual Hepatology Care with Early Palliative Care; Usual hepatology care with early palliative care	Behavioral: LiverPAL; The intervention include integrating early palliative care with usual hepatology care to evaluate and treat patients' symptoms, enhance their illness and prognostic understanding, support their coping, and coordinate their serious illness, transitional, and end-of-life care.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient Quality of Life (Functional Assessment of Chronic Illness Therapy - Palliative Care, FACIT-Pal) up t0 4 weeks	Compare patient quality of life (FACIT-Pal) scores up to 4 weeks adjusting for baseline quality of life scores between the study arms. Score range 0-184 with higher scores indicating better quality of life.	Up to 4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient FACIT-Pal Score longitudinally between study arms	Compare patient quality of life (FACIT-Pal) scores longitudinally between the study arms. Score range 0-184 with higher scores indicating better quality of life.	Up to 6 months
Patient Symptom Burden (revised Edmonton Symptom Assessment Scale, ESAS-r)	Compare patient symptom burden scores (ESAS-r) between the study arms. Score range 0-100 with higher scores indicating higher symptom burden.	Up to 6 months
Patient Depression Symptoms (Hospital Anxiety and Depression Scale, HADS-D)	Compare patient depression symptoms (HADS-D) between the study arms. Score range 0-21 with higher scores indicating higher depression symptoms.	Up to 6 months
Patient Anxiety Symptoms (Hospital Anxiety and Depression Scale, HADS-A)	Compare patient anxiety symptoms (HADS-A) between study arms. Score range 0-21 with higher scores indicating higher anxiety symptoms.	Up to 6 months
Patient Quality of Life (PROMIS-29+2)	Compare patient quality of life (PROMIS-29+2) scores between study arms. Scores range 4-20 for raw items and 2-10 for cognitive function, with a higher score represents more of the concept being measured. Raw scores are translated into standardized T-scores.	Up to 6 months
Patient End-of-Life (EOL) Care Communication with Caregivers	"Has [participant] talked with [participant's] family or friends about the kind of medical care [participant] would want if [participant] were very sick or near the end of life?"	Final assessment prior to patient death or at 6 months
Patient End-of-Life (EOL) Care Communication with Clinicians	"Has [participant] talked with [participant's] doctor about the kind of medical care [participant] would want if [participant] were very sick or near the end of life?"	Final assessment prior to patient death or at 6 months
Documentation of Patient End-of-Life (EOL) Care Preferences	Compare documentation of EOL care preferences in the electronic health record between study arms since baseline.	After patient death, up to 60 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient End-of-Life (EOL) Care	Compare rate of receipt of intensive EOL care (renal replacement therapy, mechanical ventilation, and/or cardiopulmonary resuscitation or death in the intensive care unit) between study arms.	Within 30 days of patient death
Caregiver Quality of Life (PROMIS-29+2)	Compare caregiver quality of life (PROMIS-29+2) between study arms. Scores range 4-20 for raw items and 2-10 for cognitive function, with a higher score represents more of the concept being measured. Raw scores are translated into standardized T-scores.	Up to 6 months
Caregiver Depression Symptoms (Hospital Anxiety and Depression Scale, HADS-D)	Compare caregiver depression symptoms (HADS-D) between study arms. Score range 0-21 with higher scores indicating higher depression symptoms.	Up to 6 months
Caregiver Burden (Zarit Burden Index 12, ZBI-12)	Compare caregiver burden scores (ZBI-12) between study arms. Score range 0-48 with higher scores indicating higher caregiver burden.	Up to 6 months
Quality of Life Near Death (QOD)	Bereaved caregivers will be asked "Just prior to the death of [the patient] (eg, his/her last week; when last seen), how would [participant] rate [the patient's] level of…" (1) "psychological distress?" (0 = none; 10 = extremely upset); (2) "physical distress?" (0 = none; 10 = extremely distressed); and (3) "overall quality of life in the last week of life/death?" (0 = worst possible; 10 = best possible). Ratings for these three items will be averaged (with reverse coding for the psychological and physical distress items). Scores range 0-10 with higher composite scores representing better QOD.	After patient death, up to 60 months
Prolonged Grief Disorder (PG-13-R)	Compare rates of prolonged grief disorder (PG-13-R) among bereaved caregivers between study arms. Score range 10-50 for symptom items with higher scores indicating worsening symptoms.	At least 12 months after patient death, up to 60 months
Healthcare Utilization at End-of-Life - Hospice	Compare rates of hospice utilization (yes/no) between study arms.	After patient death, up to 60 months
Healthcare Utilization at End-of-Life - Hospice length of stay	Compare number of days in hospice for patients admitted to hospice between study arms.	After patient death, up to 60 months
Healthcare Utilization - Days alive and out of the hospital	Compare days alive and out of the hospital at 6 months (180 days) after randomization	Up to 6 months
Healthcare Utilization - liver transplantation	Compare rates of liver transplantation (yes/no) between study arms	Up to 60 months
Patient Coping (Brief COPE)	Compare patient coping using the Brief Cope questionnaire between study arms. We will administer 14 items of the Brief COPE comprising seven subscales (active coping, use of emotional support, positive reframing, acceptance, behavioral disengagement, denial, and self-blame). Higher scores on each subscale indicate more use of that particular coping strategy.	Up to 6 months
Caregiver Coping (Brief COPE)	Compare caregiver coping using the Brief Cope questionnaire between study arms. We will administer 14 items of the Brief COPE comprising seven subscales (active coping, use of emotional support, positive reframing, acceptance, behavioral disengagement, denial, and self-blame). Higher scores on each subscale indicate more use of that particular coping strategy.	Up to 6 months
Patient Feeling Heard and Understood Scale	We will use the validated 4-item scale "Feeling Heard and Understood" as a self-reported measure capturing seriously ill patients' global assessment of their health care quality in the hospital environment. Response options range from 0 (not at all true) to 4 (completely true) for a score range of 0-16.	Up to 6 months
Caregiver Feeling Heard and Understood Scale	We will use the validated 4-item scale "Feeling Heard and Understood" as a self-reported measure capturing seriously ill patients' caregivers' global assessment of their loved one's health care quality in the hospital environment. Response options range from 0 (not at all true) to 4 (completely true) for a score range of 0-16.	Up to 6 months
Caregiver Anxiety Symptoms (Hospital Anxiety and Depression Scale, HADS-A) between study arms.	Compare caregiver anxiety symptoms (HADS-A) between study arms. Score range 0-21 with higher scores indicating higher anxiety symptoms.	Up to 6 months
Receipt of goal-concordant end-of-life care - patient wishes followed	Bereaved caregivers will be asked "In [participant's] opinion, to what extent were [the patient's] wishes followed in the medical care received in the last month of life?" Receipt of goal-concordant end-of-life care - patient wishes followed will be defined as care that "followed patients' wishes a great deal."	At least 1 month after patient death, up to 3 months

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Investigators: Principal Investigator: Nneka Ufere, MD MSCE, Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 20, 2023
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2027

Study Registration Dates

• First Submitted: August 11, 2023
• First Submitted That Met QC Criteria: August 11, 2023
• First Posted (Actual): August 18, 2023

Study Record Updates

• Last Update Posted (Estimated): December 7, 2023
• Last Update Submitted That Met QC Criteria: December 1, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Failure; Hepatic Insufficiency; Pathologic Processes; Liver Diseases; End Stage Liver Disease; Fibrosis; Liver Cirrhosis
• Other Study ID Numbers: 2023P001894; 80736 (Other Grant/Funding Number: Robert Wood Johnson Foundation); 242379 (Other Grant/Funding Number: Cambia Health Foundation); 243432 (Other Grant/Funding Number: American Association for the Study of Liver Diseases); 236965 (Other Grant/Funding Number: Massachusetts General Hospital Executive Committee on Researrch)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No