Decompensated Cirrhosis of Liver, End Stage Liver Disease
Conditions
Keywords
palliative care, hepatology, decompensated cirrhosis
Brief 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. 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
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.
Interventions
OTHERPalliative 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
Sponsors
Patient-Centered Outcomes Research Institute
Albert Einstein Healthcare Network
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Masking description
The study investigators were masked to comparative outcomes measures until the study was completed and database was locked.
Intervention 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)
Eligibility
Sex/Gender
ALL
Age
18 Years to 120 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Quality of Life (QOL) | Mean change in FACT-Hep total score from baseline to 3 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Patient's Depression Severity | Change in PHQ-9 scores from baseline to 3 months | 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. |
| Patient Satisfaction | Change in FAMCARE-P scores from baseline to 3 months. | 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. |
| Distress | Change in Distress from baseline to 3 months | Distress thermometer (DT) ranks level of distress from 0- 10, Higher scores reflect higher distress. This is for patients only. |
| Goal Concordant Care Questionnaire/ GCC (Patients) | Change in GCC scales from baseline to 3 months | 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. |
| Patient's Symptom Burden | Change in ESAS total score from baseline to 3 months | 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. |
| Caregiver Quality of Life | Change in caregiver QoL from baseline to 3 months | 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. |
| Goal Concordant Care/ GCC (Caregivers) | Change in GCC from baseline to 3 months | 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. |
| Mortality Over 12 Months. | Survival over 12 months | Number of Patients that Died from Baseline to 12 Month. |
| Caregiver Burden (Completed by the Caregivers of Patients Who Were Enrolled as a Dyad). Caregivers Were Consented Separately. | Change in ZBI-12 scores from baseline to 3 months | 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. |
Countries
United States
Participant flow
Recruitment details
This study enrolled patients and caregivers separately. 935 Patients ( 516 in Model 1 and 419 in Model 2) and 559 caregivers (310 in Model 1 and 249 in Model 2) were enrolled. Recruitment occured from January 2019 to March 2025, with completion of data collection and database lock by June 30, 2025. Each row represents the patient and caregiver characteristics based on the actual enrollment numbers.
Pre-assignment details
This study consented and enrolled patients and caregivers separately. 935 Patients ( 516 in Model 1 and 419 in Model 2) and 559 caregivers (310 in Model 1 and 249 in Model 2) were enrolled.
Participants by arm
| Arm | Count |
|---|---|
| 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.
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 | 826 |
| 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
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 | 668 |
| Total | 1,494 |
Baseline characteristics
| Characteristic | Model 1: Consultative Palliative Care | Total | Model 2: Trained Hepatologist- Led PC |
|---|---|---|---|
| Age, Continuous Caregivers | 58 years STANDARD_DEVIATION 14.2 | 58 years STANDARD_DEVIATION 14.2 | 58 years STANDARD_DEVIATION 14.2 |
| Age, Continuous Patients | 64 years STANDARD_DEVIATION 10 | 63 years STANDARD_DEVIATION 10.3 | 62 years STANDARD_DEVIATION 10.4 |
| FACT-Hep total score | 118.2 units on a scale STANDARD_DEVIATION 28 | 116.1 units on a scale STANDARD_DEVIATION 28.2 | 113.4 units on a scale STANDARD_DEVIATION 28.1 |
| Race (NIH/OMB) Caregiver participants American Indian or Alaska Native | 2 Participants | 4 Participants | 2 Participants |
| Race (NIH/OMB) Caregiver participants Asian | 7 Participants | 10 Participants | 3 Participants |
| Race (NIH/OMB) Caregiver participants Black or African American | 50 Participants | 80 Participants | 30 Participants |
| Race (NIH/OMB) Caregiver participants More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Caregiver participants Native Hawaiian or Other Pacific Islander | 3 Participants | 3 Participants | 0 Participants |
| Race (NIH/OMB) Caregiver participants Unknown or Not Reported | 0 Participants | 16 Participants | 16 Participants |
| Race (NIH/OMB) Caregiver participants White | 248 Participants | 446 Participants | 198 Participants |
| Race (NIH/OMB) Patient participants American Indian or Alaska Native | 7 Participants | 11 Participants | 4 Participants |
| Race (NIH/OMB) Patient participants Asian | 7 Participants | 11 Participants | 4 Participants |
| Race (NIH/OMB) Patient participants Black or African American | 87 Participants | 147 Participants | 60 Participants |
| Race (NIH/OMB) Patient participants More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Patient participants Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Patient participants Unknown or Not Reported | 6 Participants | 24 Participants | 18 Participants |
| Race (NIH/OMB) Patient participants White | 409 Participants | 741 Participants | 332 Participants |
| Sex: Female, Male Caregivers (separate from patients) Female | 244 Participants | 430 Participants | 186 Participants |
| Sex: Female, Male Caregivers (separate from patients) Male | 66 Participants | 129 Participants | 63 Participants |
| Sex: Female, Male Patients Female | 123 Participants | 275 Participants | 152 Participants |
| Sex: Female, Male Patients Male | 393 Participants | 660 Participants | 267 Participants |
| Zarit Burden Interview- 12 | 8.7 units on a scale STANDARD_DEVIATION 8.2 | 9.2 units on a scale STANDARD_DEVIATION 8.2 | 10.0 units on a scale STANDARD_DEVIATION 8.2 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 84 / 516 | 81 / 419 |
| other Total, other adverse events | 0 / 516 | 0 / 419 |
| serious Total, serious adverse events | 0 / 516 | 0 / 419 |
Outcome results
Primary
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.
Time frame: Mean change in FACT-Hep total score from baseline to 3 months
Population: Modified Intention to treatment population excludes patients who got a liver transplant or were transferred to Hospice within 3 months of enrollment (i.e. before completion of intervention).
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Model 1: Consultative Palliative Care | Quality of Life (QOL) | 7.02 score on a scale |
| Model 2: Trained Hepatologist- Led PC | Quality of Life (QOL) | 8.01 score on a scale |
Secondary
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.
Time frame: Change in ZBI-12 scores from baseline to 3 months
Population: Caregivers were enrolled separately. The study enrolled patients with caregivers or patients alone.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Model 1: Consultative Palliative Care | Caregiver Burden (Completed by the Caregivers of Patients Who Were Enrolled as a Dyad). Caregivers Were Consented Separately. | -0.69 score on a scale |
| Model 2: Trained Hepatologist- Led PC | Caregiver Burden (Completed by the Caregivers of Patients Who Were Enrolled as a Dyad). Caregivers Were Consented Separately. | 0.73 score on a scale |
Secondary
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.
Time frame: Change in caregiver QoL from baseline to 3 months
Population: Modified Intention to treatment population excludes caregivers whose patients who got a liver transplant or were transferred to Hospice within 3 months of enrollment (i.e. before completion of intervention).
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Model 1: Consultative Palliative Care | Caregiver Quality of Life | Physical Health Summary Score | 0.19 score on a scale |
| Model 1: Consultative Palliative Care | Caregiver Quality of Life | Mental Health Summary Score | -0.10 score on a scale |
| Model 2: Trained Hepatologist- Led PC | Caregiver Quality of Life | Physical Health Summary Score | 0.18 score on a scale |
| Model 2: Trained Hepatologist- Led PC | Caregiver Quality of Life | Mental Health Summary Score | -0.49 score on a scale |
Secondary
Distress
Distress thermometer (DT) ranks level of distress from 0- 10, Higher scores reflect higher distress. This is for patients only.
Time frame: Change in Distress from baseline to 3 months
Population: Modified Intention to treatment population excludes patients who got a liver transplant or were transferred to Hospice within 3 months of enrollment (i.e. before completion of intervention).
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Model 1: Consultative Palliative Care | Distress | -0.34 score on a scale |
| Model 2: Trained Hepatologist- Led PC | Distress | -0.27 score on a scale |
Secondary
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.
Time frame: Change in GCC from baseline to 3 months
Population: Modified Intention to treatment population excludes caregivers of patients who got a liver transplant or were transferred to Hospice within 3 months of enrollment (i.e. before completion of intervention).
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Model 1: Consultative Palliative Care | Goal Concordant Care/ GCC (Caregivers) | Goals of Care Conversations (GoC) scale | 0.21 score on a scale |
| Model 1: Consultative Palliative Care | Goal Concordant Care/ GCC (Caregivers) | Care Concordant with Preferences (CCP) scale | 0.32 score on a scale |
| Model 2: Trained Hepatologist- Led PC | Goal Concordant Care/ GCC (Caregivers) | Goals of Care Conversations (GoC) scale | 0.45 score on a scale |
| Model 2: Trained Hepatologist- Led PC | Goal Concordant Care/ GCC (Caregivers) | Care Concordant with Preferences (CCP) scale | 0.87 score on a scale |
Secondary
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.
Time frame: Change in GCC scales from baseline to 3 months
Population: Modified Intention to treatment population excludes patients who got a liver transplant or were transferred to Hospice within 3 months of enrollment (i.e. before completion of intervention).
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Model 1: Consultative Palliative Care | Goal Concordant Care Questionnaire/ GCC (Patients) | Goals of Care Conversations (GoC) scale | 0.17 score on a scale |
| Model 1: Consultative Palliative Care | Goal Concordant Care Questionnaire/ GCC (Patients) | Care Concordant with Preferences (CCP) scale | 0.53 score on a scale |
| Model 2: Trained Hepatologist- Led PC | Goal Concordant Care Questionnaire/ GCC (Patients) | Goals of Care Conversations (GoC) scale | 0.35 score on a scale |
| Model 2: Trained Hepatologist- Led PC | Goal Concordant Care Questionnaire/ GCC (Patients) | Care Concordant with Preferences (CCP) scale | 0.71 score on a scale |
Secondary
Mortality Over 12 Months.
Number of Patients that Died from Baseline to 12 Month.
Time frame: Survival over 12 months
Population: All enrolled patients are included in this analysis. We report the number of patients who died within 12 months from enrollment (as count of participants).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Model 1: Consultative Palliative Care | Mortality Over 12 Months. | 84 Participants |
| Model 2: Trained Hepatologist- Led PC | Mortality Over 12 Months. | 81 Participants |
Secondary
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.
Time frame: Change in FAMCARE-P scores from baseline to 3 months.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Model 1: Consultative Palliative Care | Patient Satisfaction | 0.91 score on a scale |
| Model 2: Trained Hepatologist- Led PC | Patient Satisfaction | 3.37 score on a scale |
Secondary
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.
Time frame: Change in PHQ-9 scores from baseline to 3 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Model 1: Consultative Palliative Care | Patient's Depression Severity | -0.90 score on a scale |
| Model 2: Trained Hepatologist- Led PC | Patient's Depression Severity | -1.18 score on a scale |
Secondary
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.
Time frame: Change in ESAS total score from baseline to 3 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Model 1: Consultative Palliative Care | Patient's Symptom Burden | -5.31 score on a scale |
| Model 2: Trained Hepatologist- Led PC | Patient's Symptom Burden | -7.52 score on a scale |