Can Aspirin Reduce the Risk of HCC in Cirrhosis: The AspiRe HCC Trial (AspiRe HCC)

Can Aspirin Reduce the Risk of Hepatocellular Carcinoma (HCC) in Participants With Cirrhosis: a Multicentre, Placebo-controlled Clinical Trial - The AspiRe HCC Trial

This clinical trial is testing whether taking a low dose aspirin tablet (100 mg) once a day can help prevent liver cancer (hepatocellular carcinoma, HCC) in people who have cirrhosis, which is severe scarring of the liver. People with cirrhosis have a higher risk of developing HCC. Currently, there is no approved treatment that prevents liver cancer in this group.

Research from around the world suggests that low dose aspirin might reduce the risk of liver cancer by up to half and is safe for people with cirrhosis. However, it is not yet approved for this purpose in Australia. A trial is needed to find out if aspirin really can prevent liver cancer in people with cirrhosis and is safe for these people to use.

890 people from up to 7 hospitals across Australia will take part.

Participants will take medication daily for 4 years. They will be randomly allocated to either aspirin or a placebo (dummy pill).

Participants will continue to have their regular 6 monthly clinic visit with liver ultrasounds and blood tests as part of their normal care.

If at any time liver cancer is found, they will stop the trial.

Participants will also complete some extra tasks:

• Record missed doses or other medications in a small diary.
• Fill in two short quality of life surveys each year.
• Return their medication and diary at their regular 6 monthly appointments.
• In Western Australia only: they will be invited to give optional blood samples for future research.

Study Overview

• Status: Not yet recruiting
• Conditions: Liver Cirrhosis
• Intervention / Treatment: Drug: Low-dose aspirin; Drug: Placebo Comparator

Detailed Description

The AspiRe HCC trial is a large clinical study designed to find out whether daily low-dose aspirin (100 mg) can help prevent hepatocellular carcinoma (HCC)-the most common form of liver cancer-in people who already have liver cirrhosis.

HCC rates are rising in Australia and worldwide and more than 90% of HCC cases occur in people with cirrhosis. Less than 20% of people with cirrhosis have HCC diagnosed early enough for it to be curable. Diagnosis of HCC at an early stage increases the chances of being able to cure it or stop it from growing or spreading. Previous research suggests aspirin may reduce the risk of developing HCC by 50-70%, with stronger benefits in people who already have cirrhosis.

Ideally, we need to prevent HCC developing in the first place. However, there is no current treatment to preventing HCC in people with cirrhosis.

Experimental studies in animals and humans have shown that that aspirin treatment is safe and may prevent HCC, reducing the risk by at least 50% in people with cirrhosis. Studies from around the world have shown that people taking low-dose aspirin (100 mg daily or sometimes called "mini-aspirin") for other reasons (such as for heart disease or stroke prevention) have a much lower risk of developing HCC. Importantly, people who use aspirin in these settings do not seem to have any increase in the rates of side effects compared to people who do not take aspirin.

If proven effective, aspirin could become a simple and affordable preventative treatment, potentially saving hundreds of lives each year and reducing healthcare costs.

People with lived experience of cirrhosis and liver cancer have been involved in designing and reviewing the study to ensure it is relevant, ethical and meaningful. They will continue contributing as members of the Trial Steering Committee.

This trial is a multi-centre, prospective, pragmatic 4-year RCT of aspirin versus placebo therapy in 890 stable, well-compensated cirrhotic participants attending hospital outpatient clinics and otherwise receiving standard of care treatment at up to seven sites across Australian.

Participants will be randomly assigned in a 1:1 ratio to either a 100 mg tablet of enteric-coated aspirin daily or placebo therapy, according to a block-randomisation procedure and their date of enrolment in the study.

Participants will continue their usual care. At each 6 monthly standard of care visit, during their 4 years on study, the site team will enter data into a REDCap database:

• Routine blood test results
• Routine liver imaging for monitoring of occurrence of HCC (ultrasound, CT, or MRI)
• Routine liver elastography once a year
• Any hospital admissions or new symptoms
• QOL information via two surveys' (Ed-5q-5L and CLDQ)

Western Australian participants may consent to optional additional blood sample collection, at baseline and end of trial, for a biological specimen repository to support future research.

All participants will be invited to consent to provision of their MBS/PBS data during the trial, to analyse the cost of treatment and life years saved.

Any participant who is diagnosed with HCC during their time on trial has reached the primary endpoint and will cease their participation

• Study Type: Interventional
• Enrollment (Estimated): 890
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Rachel Galettis, PhD; Phone Number: +61 (08) 9266 9509; Email: rachel.galettis@curtin.edu.au
• Study Contact Backup: Name: Jacquita Affandi, PhD; Phone Number: +61 (08) 9266 5860; Email: jacquita.affandi@curtin.edu.au

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Provide written informed consent to participate in the trial according to ICH GCP (R3) and national/local regulations.
• Diagnosed with liver cirrhosis for at least 6 months
• Has a current Child-Pugh score ≤6 (Child A - clinically and biochemically compensated cirrhosis)
• Has been participating in ultrasound or non-ultrasound (computed tomography (CT) or magnetic resonance imaging (MRI)) based surveillance for at least 6 months prior to entry.
• Has not had any focal lesions, other than haemangiomas, detected during the past 6 months.

Exclusion Criteria:

• Any of the following:

  • autoimmune liver disease.
  • primary biliary cholangitis.
  • primary sclerosing cholangitis.
  • prior HCC
  • alcohol consumption >3 standard drinks per day in men and 2 standard drinks per day in women.
  • currently taking a nonsteroidal anti-inflammatory drug, anticoagulant drugs, non-vitamin K anticoagulant frugs, or other antiplatelet drugs, including aspirin, within the last 6 months.
  • a known bleeding disorder
  • a platelet count <50 x 109/L.
  • known history or endoscopic evidence of high risk oesophageal (grade 2 or higher) or gastric varices or, a history of bleeding varices.
  • chronic iron deficiency anaemia.
  • a prior history of liver decompensation or liver transplantation.
  • known peptic ulcer disease.
  • chronic kidney disease with eGFR <50ml/min; a contraindication to aspirin.
  • Any participant considered by the PI to be deemed unlikely to complete the study due to other comorbid conditions or poor compliance will also be excluded.

Pregnancy:

• Whilst low dose aspirin is considered safe in pregnancy, male and female participants of child-bearing potential are recommended use effective contraception during this trial.
• Any female participants who fall pregnant during the trial will be withdrawn if their treating obstetric doctor advises that you should do so.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Low dose Aspirin; Low dose aspirin, 100mg, once daily for 4 years or until diagnosis of HCC	Drug: Low-dose aspirin; a capsule containing100mg Low Dose Aspirin; Other Names: acetylsalicylic acid
Placebo Comparator: Placebo; Placebo, once daily for 4 years or until diagnosis of HCC	Drug: Placebo Comparator; an identical capsule containing no active drug

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall incidence of HCC in participants receiving aspirin or placebo	Incidence of HCC, which is defined as the presence or absence of HCC at study completion in participants receiving aspirin compared to placebo	Randomisation to End of study - 4 years treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Adverse Events	Total number and type of adverse events, reported using CTCAE terminology and relatedness, in participants receiving aspirin compared to placebo	Randomisation to End of study - 4 years treatment
Treatment Compliance	Adherence to treatment assessed by drug accountability and patient diary for participants receiving aspirin compared to placebo	Randomisation to End of study - 4 years treatment
Hospital admissions for clinical complications of cirrhosis	Total number of hospital admissions for clinical complications of cirrhosis occurring in participants receiving aspirin compared to placebo	Randomisation to End of study - 4 years treatment
Quality of Life (QOL) - EQ-5D-5L	The EQ-5D-5L is a short, easy-to-use, self-reported measure of health status. It includes two components: a health questionnaire and a visual analogue scale (EQ-VAS). The EQ-VAS asks respondents to rate their overall current health on a vertical scale ranging from "the best health you can imagine" to "the worst health you can imagine", providing a quantitative measure of perceived health and allowing changes over time to be monitored. The questionnaire assesses health across five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has five response levels, from no problems to extreme problems or inability. Responses are combined into a single utility score representing overall health status. Higher scores indicate worse quality of life. This utility score will be used to calculate Quality-Adjusted Life Years (QALYs) and results for participants treated with aspirin compared to placebo.	Randomisation to End of study - 4 years treatment
Quality of Life (QOL) - CLDQ	The Chronic Liver Disease Questionnaire (CLDQ) is a validated, self-reported measure of health-related quality of life in people with chronic liver disease. It comprises 29 items across six domains: abdominal symptoms, fatigue, emotional health, activity/energy, systemic symptoms, and worry. Each item is rated on a 7-point Likert scale ranging from "all of the time" to "none of the time", with higher scores indicating better quality of life. The higher the number, the better the quality of life. Results of participants treated with aspirin will be compared to those treated with placebo.	Randomisation to End of study - 4 years treatment
Resource Utilization and Cost-effectiveness of Treatment	Cost utility analysis of aspirin compared to placebo in preventing HCC in people with cirrhosis will be performed. The following data sources will be used to calculate this outcome measure. National Hospital Cost Data Collection (NHCDC) and Medical Cost Finder, Australian Refined Diagnosis Related Groups (AR-DRGs), Medicare Benefits Scheme (MBS), Pharmaceutical Benefits Scheme (PBS). AR-DRGs are large data cubes that represents the costing for a class of patients with similar clinical conditions requiring similar hospital service MBS/PBS data is Australian Government collected data recording prescriptions and health service use for the duration of participants time in the study. Health utilities scores will come from the CLDQ and EQ-5D-5L.	Randomisation to End of study - 4 years treatment

Collaborators and Investigators

• Sponsor: Curtin University
• Investigators: Principal Investigator: John K Olynyk, BMedSc MBBS FRACP MD FAASLD, Curtin University

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): June 30, 2030
• Study Completion (Estimated): June 30, 2030

Study Registration Dates

• First Submitted: March 19, 2026
• First Submitted That Met QC Criteria: April 13, 2026
• First Posted (Actual): April 14, 2026

Study Record Updates

• Last Update Posted (Actual): April 14, 2026
• Last Update Submitted That Met QC Criteria: April 13, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Cancer; Carcinoma; Cirrhosis; Hepatic; Liver; Hepatocellular
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Digestive System Diseases; Liver Diseases; Neoplasms, Glandular and Epithelial; Pathological Conditions, Signs and Symptoms; Neoplasms; Carcinoma; Fibrosis; Liver Cirrhosis; Organic Chemicals; Hydrocarbons; Hydrocarbons, Cyclic; Hydrocarbons, Aromatic; Phenols; Benzene Derivatives; Salicylates; Hydroxybenzoates; Aspirin
• Other Study ID Numbers: AspiRe HCC (RES-69007); 2041836 (Other Grant/Funding Number: National Health and Medical Research Council (NHMRC)); U1111-1335-6237 (Other Identifier: World Health Organization Universal Trial Number (UTN))

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