Primary sclerosing cholangitis with or without concomitant inflammatory bowel disease included in an unlimited surveillance program for hepatobiliary and colorectal malignancy
Conditions
Interventions
Trade Name: Ursofalk
Product Name: Ursofalk
Pharmaceutical Form: Capsule, hard
Sponsors
Sahlgrenska Academy
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Inclusion in the SILK PSC surveillance program 2. MRCP or ERCP confirmed large-duct PSC 3. ALP at screening >1.5x ULN (at =2 opportunities during =six months) 4. PSC-associated symptoms at ALP =1.5x ULN 5. Currently not taking UDCA for =3 months. Ongoing medication with UDCA is withdrawn for three months. These patients have an additional visit (V-1) three months before V1 (start of UDCA) 6. Age = 18 years 7. Written informed consent 8. Women with childbearing potential may participate in the trial since UDCA is considered save in pregnancy according to EASL and Swedish guidelines, at least in the second and third trimester, and is the first-line treatment in women with intrahepatic cholestasis of pregnancy (ICP). Pregnant women are advised to temporarily stop treatment with UDCA in the first trimester. 9. If a woman with PSC who is a UDCA non-responder becomes pregnant, UDCA may be administered for the treatment of ICP according to EASL and Swedish guidelines. UDCA then is withdrawn after delivery. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 450 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 50
Exclusion criteria
Exclusion criteria: 1. Chronic liver disease other than PSC (PBC, viral hepatitis, autoimmune liver disease, hemochromatosis, homozygous alpha1-antitrypsin deficiency and Wilson disease) 2. Evidence of a secondary cause of sclerosing cholangitis 3. Presence of complications or clinically significant hepatic decompensation of PSC: • History of liver transplantation, current placement on a liver transplant list or current MELD score = 15 • Portal hypertension with complications, including: known gastric or large esophageal varices, history of variceal bleeds, poorly controlled or diuretic resistant ascites, transjugular intrahepatic portosystemic shunt [TIPS]), or hepatic encephalopathy • Cirrhosis with complications, including history or presence of: spontaneous bacterial peritonitis, hepatocellular carcinoma • Hepatorenal syndrome (type I or II) 4. Presence of cholangiocarcinoma or other malignancy 5. Alcohol abuse (as assessed by the investigator) 6. Documented intolerance of UDCA, e.g., severe diarrhoea 7. Suggested non-compliance with the protocol.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: (i) To assess in incidence of biliary malignancy as assessed by surveillance MR/MRCP in patients with PSC with and without response to UDCA (ii) To assess in incidence of colorectal malignancy as assessed by surveillance colonoscopy in patients with PSC with and without response to UDCA ;Secondary Objective: (i) To assess safety and tolerability of 17-23 mg/kg/d of UDCA (ii) To assess the effect of UDCA on progression of liver failure (MELD score) (iii) To assess the effect of UDCA on development of complications of liver cirrhosis (iv) To assess the effect of UDCA on liver transplant-free survival (v) To assess the effect of UDCA on liver biochemistry (ALP, bilirubin, ALT, AST) (vi) To assess the effect of UDCA on inflammation markers CRP, TNFa, IL-6 (vii) To assess the effect of UDCA on tumor markers CA19-9 and CEA (viii)To assess the effect of UDCA on inflammatory bowel disease activity (MAYO scores) (ix) To assess the effect of UDCA on pruritus as assessed by visible analogue scale (VAS) (x) To assess the effect of UDCA on serum and fecal bile acids (xi) To assess the effect of UDCA on gut microbiota diversity ;Primary end point(s): - any hepatobiliary malignancy including low-grade dysplasia detected by surveillance MRCP - any colorectal malignancy including low-grade dysplasia detected by surveillance colonoscopy ;Timepoint(s) of evaluation of this end point: Every year after annual MRCP and colonoscopy | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - any incidental hepatobiliary malignancy including high-grade dysplasia - any incidental colorectal malignancy including high-grade dysplasia - progress to Child C liver cirrhosis - pruritus refractory to anion exchange raisins - liver transplantation ;Timepoint(s) of evaluation of this end point: Every year after annual MRCP and colonoscopy | — |
Countries
Sweden
Contacts
Public ContactHanns-Ulrich Marschall
Sahlgrenska Acaedmy
Outcome results
None listed