Asp-PSC Trial

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 Protocol

Asp-PSC Patient Information Sheet

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 exceed 20 mg/kg/day
7. Must have had a colonoscopy within the last year of the first day of screening 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 a 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, nonalcoholic 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, or is being actively assessed for liver transplant, or is listed for a liver transplant.

5. Had any of the following procedures: colonic resection of any nature, including those with a defunctioning colostomy.

6. Known diagnosis of alcohol related liver disease
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. Known diagnosis of Lynch Syndrome or Li Fraumeni Syndrome
14. Vaccination for varicella zoster in the six weeks prior to screening period
15. Known allergy to aspirin
16. A history of NSAID/ aspirin induced asthma and nasal polyps
17. Chronic daily oral non-steroidal anti-inflammatory (NSAIDs) drug usage (continuously for 3 weeks prior to the first day of screening).

18. History of haemophilia and/or other bleeding disorders where aspirin is contraindicated
19. Taking other anti-platelet or anti-coagulant medication (e.g., clopidogrel, prasugrel, warfarin, apixaban, rivaroxaban, dabigatran or therapeutic heparin preparations)

20. Active, or history of recurrent peptic ulcer
21. Patients who are suffering from severe active gout
22. Severe renal impairment
23. Taking methotrexate at a dose of >15mg/week

Taking part in the study

If you are interested in taking part in the study, please see below for hospital study sites and contact email addresses. New hospital sites are added each month, so please do keep checking this website. Alternatively, contact Martine at research@pscsupport.org.uk, if you require more information.

Funding

This project is funded by Cancer Research UK.