Effect of Aspirin on Reducing Cancer & Improving Outcomes in Primary Sclerosing Cholangitis

Trial Aim

Is low dose aspirin is safe and effective in reducing the risk of cancer, as well as the need for liver transplantation, and in increasing overall survival, in people with both PSC and IBD.

Design

• Investigator led
• Double-blind
• Randomised Controlled Trial
• Aspirin vs Placebo (2:1)
• For 5-years
• Multi-centre
• 968 patients needed

Patient Information Sheet

Asp-PSC Patient Information Sheet

Asp-PSC Protocol

Method

Patients will be given an appropriate time period to consider participation (at least 24 hours). Written consent will be obtained from those patients who agree to participate and randomisation will be performed using OpenClinica eCRF. At each recruiting centre, a log of all approached and screened patients will be kept.

Size of trial

968 patients will be recruited over 60 centres over 5 years.

Eligibility

Inclusion criteria

1. Age 18 years or above
2. Able to give written and informed consent.
3. Must have an established clinical diagnosis of large duct PSC-based on a standard disease definition of typical cholangiography findings on endoscopic retrograde cholangiography (ERCP) or magnetic resonance cholangiography (MRCP).
4. An established diagnosis of concomitant colonic IBD either in a pattern of Ulcerative Colitis, Crohn’s disease or IBD unclassified.
5. Patients must be at least one-year post PSC diagnosis.
6. If pre-treated with ursodeoxycholic acid (UDCA) – UDCA therapy should remain at a stable dose for 12 weeks prior to screening, and not exceeding 20mg/kg/day.
7. Must have had a colonoscopy within the last year of randomisation date as part of routine clinical care. If not this must be done within the screening interval.
8. If a patient has cirrhosis, they must have undertaken a hepatobiliary ultrasound (US), MRCP scan, magnetic resonance imaging (MRI) liver or regional computerised tomography (CT) scan within 6 months of screening date as part of routine clinical care. If not, this must be done within the screening interval.
9. If non-cirrhotic, then the patient must have had an US, MRCP, dynamic MRI or regional CT within the last 12 months as part of routine clinical care. If not, this must be done within the screening interval.

Exclusion criteria

1. Evidence of concomitant disease(s) that causes secondary sclerosing cholangitis.
2. Evidence of any of the following diseases: IgG4 related disease, PBC, acute or chronic viral hepatitis, alcohol-related liver disease, Wilson disease, Budd-Chiari syndrome, portal vein thrombosis, alpha-1-antitrypsin disease, hepatic sarcoidosis, cystic fibrosis, Progressive familial intrahepatic cholestasis (PFIC), hereditary haemochromatosis, non-alcoholic steatohepatitis (NASH) – those with simple hepatic steatosis without evidence of NASH or liver fibrosis secondary to fatty liver disease are allowed to participate, other metabolic liver disease, active malignancy in the last five years (except treated/excised non-melanomatous skin cancer).
3. Have a previous diagnosis of colorectal cancer, cholangiocarcinoma, gallbladder cancer at any time point.
4. Has received a liver transplant, has been referred for liver transplant assessment, or is listed for a liver transplant.
5. Had any of the following procedures: colonic resection of any nature, including those with a defunctioning ostomy.
6. Consume more than the recommended allowance of 14 units of alcohol per week (as set out by the Department of Health).
7. Current or recent participation in any other clinical trial of an investigational medicinal product (CTIMP) within the last 6 weeks prior to first dose of aspirin/placebo
8. Already taking aspirin.
9. History of non-variceal upper gastrointestinal (GI) bleeding within one year.
10. A history of congestive cardiac failure.
11. A known diagnosis of glucose-6 -phosphate dehydrogenase.
12. Childs Pugh B or C cirrhosis
13. Untreated thyrotoxicosis or hypothyroidism
14. Familial history of a hereditary cancer syndrome, or confirmed genetic predisposition that heightens cancer risk.
15. Vaccination for varicella zoster in the six weeks prior to screening period
16. Known allergy to aspirin
17. A history of NSAID/ aspirin induced asthma and nasal polyps
18. Concurrently taking non-steroidal anti-inflammatory drugs (NSAIDs) in the four weeks prior to screening
19. History of haemophilia and/or other bleeding disorders where aspirin is contraindicated
20. Taking other anti-platelet or anti-coagulant medication (e.g., clopidogrel, prasugrel, warfarin, apixaban, rivaroxaban, dabigatran or therapeutic heparin preparations)
21. Active, or history of recurrent peptic ulcer
22. Patients who are suffering from gout
23. Severe renal impairment
24. Taking methotrexate at a dose of >15mg/week
25. Taking selective serotonin-reuptake inhibitors

Funding

This project is funded by Cancer Research UK.