Texas Hepatocellular Carcinoma Consortium (THCCC) Project 5

• ClinicalTrials.gov Identifier: NCT02582918
• Recruitment Status: Active, not recruiting
• First Posted: October 21, 2015
• Last Update Posted: May 19, 2020
• Sponsor: University of Texas Southwestern Medical Center
• Collaborators: Parkland Health and Hospital System; VA Medical Center, Houston
• Information provided by (Responsible Party): University of Texas Southwestern Medical Center

Study Description

Brief Summary:

Project 5 of the Texas HCC Consortium (THCCC) is a comparative effectiveness pragmatic randomized control trial (RCT) of outreach strategies to increase hepatocellular cancer (HCC) surveillance process completion among a socioeconomically and racially diverse cohort of Texans with cirrhosis. Through this project the investigators will implement and evaluate system-level mailed outreach interventions to identity at-risk patients with cirrhosis, promote HCC surveillance, and ensure timely follow-up of tests at UT Southwestern (UTSW) Medical Center, Parkland Health and Hospital System (PHHS), and the Houston Veterans Affairs (VA) Medical Center. The study population will include adult patients with documented or unrecognized cirrhosis and at least one outpatient clinic visit in year prior to randomization. Patients will be identified using an EMR-enabled case identification algorithm. The investigators will randomize 3000 patients (1500 per arm) identified by this algorithm to: usual care, with opportunistic visit-based HCC surveillance (Group 1); or, mailed HCC surveillance outreach with patient education and patient navigation services (Group 2).

Condition or disease	Intervention/treatment	Phase
Carcinoma, Hepatocellular; Liver Neoplasms	Behavioral: Outreach with patient education and patient navigation services	Not Applicable

Detailed Description:

Hepatocellular cancer (HCC) is the most common (≥ 95%) of liver cancers. HCC is also the fastest rising cause of cancer-related deaths in the U.S. HCC is particularly important for Texas residents. Texas has the second highest death rate from HCC in the nation. The 5-year HCC survival remains low (10-15%) and most patients get diagnosed at late stages. Texas residents notably Hispanics and African Americans are greatly affected with established HCC risk factors including hepatitis C virus, hepatitis B virus and alcoholic liver disease. Furthermore, emerging HCC risk factors, specifically the metabolic syndrome and non-alcoholic fatty liver disease (NAFLD), are exceptionally common in Texans.

The goal of the Texas Hepatocellular Carcinoma Consortium (THCCC) is to reduce the death and suffering related to liver cancer in Texas and the world through five research projects.

This protocol outlines Project 5 of the THCCC which is a comparative effectiveness randomized controlled trial of strategies to increase HCC surveillance. This is the first multi-center outreach intervention aimed at improving surveillance process completion among at-risk patients with cirrhosis.

This study is based at 3 health systems in Texas: UT Southwestern (UTSW) Medical Center, Parkland Health and Hospital System (PHHS), and the Houston Veterans Affairs (VA) Medical Center. Across these 3 sites, we will implement and evaluate system-level mailed outreach interventions to identity at-risk patients with cirrhosis, promote HCC surveillance, and ensure timely follow-up of tests. This study uses an EMR-enabled case-finding algorithm to identify patients with documented cirrhosis, using ICD-9 codes, and those with unrecognized cirrhosis, using laboratory data.

Over 3000 patients identified by this algorithm will be randomized to:

• Group 1: Usual care with opportunistic visit-based HCC surveillance.
• Group 2: Mailed HCC surveillance outreach with patient education and patient navigation services.

The Specific Aims are:

• Aim 1: Compare the clinical effectiveness of the intervention strategies to increase completion of the HCC surveillance process.
• Aim 2: Compare patient-reported satisfaction and acceptability of the HCC surveillance strategies.
• Aim 3: Evaluate whether intervention effects are moderated by patient sex, race/ethnicity, socioeconomic status, health care utilization, and documented vs. unrecognized cirrhosis.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 2871 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Care Provider)
• Primary Purpose: Screening
• Official Title: Comparative Effectiveness Trial of Care Delivery Strategies for HCC Screening Process Completion
• Actual Study Start Date: March 26, 2018
• Estimated Primary Completion Date: August 2022
• Estimated Study Completion Date: August 2022

Arms and Interventions

Arm	Intervention/treatment
No Intervention: Group 1: Usual Care; Usual care with opportunistic visit-based HCC surveillance.
Experimental: Group 2: Patient Education and Patient Navigation Services; Mailed HCC surveillance outreach with patient education and patient navigation services.	Behavioral: Outreach with patient education and patient navigation services; Outreach invitations include number to call for more information about scheduling an ultrasound and alpha fetoprotein (AFP) blood test.; Patients receive up to three phone calls 2-4 weeks after invitations and a reminder call 5-7 business days before appointments.; If results are normal, the patient is invited to repeat screening in 6 months.; If suspicious mass on ultrasound or abnormal AFP level, the patient is referred for follow-up testing with triple-phase CT scan or MRI.; If CT/MRI is unremarkable, the patient is referred back for routine screening.; If HCC is confirmed, the patient and their primary care provider will be contacted with the results.; All patients diagnosed with HCC will be seen in the multi-disciplinary HCC clinic.

Outcome Measures

Primary Outcome Measures :

1. Completion of HCC surveillance process [ Time Frame: 3 years post randomization ]

   Ascertained through EMR.

   HCC surveillance process completion will be defined as:

   • normal ultrasound and AFP every 6 ± 1 months for two consecutive years,
   • abnormal ultrasound or AFP ≥20 ng/mL and follow-up diagnostic CT or MRI without HCC, then appropriate surveillance as indicated for total of 2 years, or
   • abnormal ultrasound or AFP, HCC detected on CT/MRI, and timely HCC treatment consultation.

   Effective surveillance requires repeat testing every 6 months in patients with normal tests to maximize sensitivity while minimizing patient burden.

   Patients with abnormal surveillance tests (i.e. liver mass on ultrasound or AFP ≥20 ng/mL) require 4-phase CT or MRI within 3 months, with a 3-month cut-off based on HCC tumor doubling time.

   Patients with non-contrast imaging, two-phase CT, or imaging > 3 months after abnormal tests will be coded as failure.

   Likewise, patients with HCC confirmed on CT/MRI will need HCC-directed treatment within 3 months.

2. Patient satisfaction and acceptability [ Time Frame: 3 years post randomization ]

   Assessed by 15-20 minute telephone semi-structured interviews.

   Patients will be called >24 months post-randomization to ensure interviews do not interfere with likelihood of surveillance process completion.

   The investigators will interview 30 completers and 30 non-completers from each group at each site (540 total).

   The investigators will stratify sampling to include both patients with documented cirrhosis and unrecognized cirrhosis. Likert scale items will assess reactions:

   • Participants were confused why they were referred for HCC screening
   • Participants were not given enough information to make a decision
   • Participants don't want to know if they have HCC
   • Information about HCC was new and items assessing if invitations included more, right amount, or not enough information as the participants would like.

   Interviews will also assess what HCC testing (if any) patients think they should have.

Secondary Outcome Measures :

1. Early HCC [ Time Frame: 3 years post randomization ]

   HCC will be defined by AASLD criteria and staged by Barcelona Clinic Liver Cancer (BCLC) system.

   Tumors >1 cm can be diagnosed if CT/MRI shows characteristic findings (arterial enhancement and delayed washout).

   Biopsy may be needed if imaging is not diagnostic.

   Early HCC will be defined as BCLC stage A tumors that are amenable to curative therapy.

   HCC diagnoses and stage will be ascertained from EMR data and confirmed by site investigators.

2. One-time Screening [ Time Frame: Outcomes will be adjudicated 6 months after randomization. ]
   Defined as the proportion of patients completing HCC screening within 6 months of randomization.
3. Repeat Screening [ Time Frame: Outcomes will be adjudicated 12 months after randomization. ]
   Defined as the proportion of patients completing HCC screening every 6 months within 12 months of randomization. Patients will be categorized as completed all screening (2 screening in 12 months), some screening (1 screening in 12 months), or no screening (0 screening in 12 months).

Eligibility Criteria

• Ages Eligible for Study: 21 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Adult patients (>21 years old)
• Documented cirrhosis
• Unrecognized cirrhosis
• An outpatient visit in year prior to randomization
• English or Spanish speaking

Exclusion Criteria:

• History of HCC
• History of liver transplantation
• Child Pugh C cirrhosis
• Significant comorbid conditions with life expectancy < 1 year, (e.g., extrahepatic malignancy)

Contacts and Locations

Locations

United States, Texas

University of Texas Southwestern Medical Center

Dallas, Texas, United States, 75390

Sponsors and Collaborators

University of Texas Southwestern Medical Center

Parkland Health and Hospital System

VA Medical Center, Houston

Investigators

• Principal Investigator: Amit G Singal, MD; University of Texas Southwestern Medical Center

More Information

• Responsible Party: University of Texas Southwestern Medical Center
• ClinicalTrials.gov Identifier: NCT02582918
• Other Study ID Numbers: 062015-054
• First Posted: October 21, 2015
• Last Update Posted: May 19, 2020
• Last Verified: May 2020

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University of Texas Southwestern Medical Center:

Randomized Controlled Trial; Mass Screening

Additional relevant MeSH terms:

Carcinoma; Carcinoma, Hepatocellular; Liver Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases