osartan treatment for non-alcoholic steatohepatitis (NASH)

Phase 3

Completed

• Conditions: Fibrosis resulting from non-alcoholic steatohepatitis; Digestive System; Other diseases of liver

• Registration Number: ISRCTN57849521
• Lead Sponsor: ewcastle upon Tyne Hospitals NHS Foundation Trust (UK)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2009-10-12
• Last Update Posted: 22 May 2017

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 214

Inclusion Criteria

Current inclusion criteria as of 16/06/2011:
Adults (both males and females, aged 18+) with steatohepatitis and fibrosis (Kleiner F1-F3), resulting from non-alcoholic fatty liver disease

Previous inclusion criteria:
Adults (both males and females, aged 18+) with fibrosis resulting from non-alcoholic steatohepatitis.

Exclusion Criteria

Current exclusion criteria as of 09/07/2012:
1. Refusal or inability (lack of capacity) to give informed consent
2. Average alcohol ingestion >21 units/week (males) or >14 units/week (females)
3. History or presence of Type 1 diabetes mellitus
4. Haemoglobin A1C >15.0
5. Other causes of chronic liver disease or hepatic steatosis
6. Any contra-indication to liver biopsy
7. History of or planned gastrointestinal bypass surgery
8. Hepatocellular carcinoma
9. Previous liver transplantation
10. Recent significant weight loss (>5% total body weight within last 6 months)
11. Electrolyte disturbance: potassium level outside the normal (local) range.
12. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >10 x upper limit of normal (ULN) at screening
13. Recent (within 6 months of baseline liver biopsy and screening visit) or concomitant use of agent known to cause hepatic steatosis (corticosteroids, amiodarone, methotrexate, tamoxifen, tetracycline, high dose oestrogens, valproic acid) or concomitant use of pioglitazone, fluconazole, rifampicin or any drug contra-indicated in the Losartan SmPC.
14. Introduction of metformin, glitazones, a GLP-1 agonist, Vitamin E or C, betaine, s-adenosyl methionine, ursodeoxycholic acid, silymarin, fibrate, pentoxifylline, orlistat, sibutramine or rimonabant within 3 months of baseline liver biopsy and screening visit.
15. Intolerance of angiotensin receptor blockers (ARBs) or presence of multiple allergic reactions to drugs
16. Use of angiotensin-converting enzyme (ACE) inhibitor or ARB in previous year
17. Hypotension (systolic <100, diastolic <60)
18. Renal failure (Cr >130)
19. Participation in any clinical study of an investigational agent within 30 days or five half-lives of the investigational product, whichever is longer
20. Presence of clinically relevant cardiovascular, pulmonary, gastro-intestinal, renal, hepatic, metabolic, haematological, neurological, psychiatric, systemic, ocular, gynaecologic or any acute infectious disease or signs of acute illness that, in the opinion of the investigator, might compromise the patient's safe participation in the trial
21. Presence or history of cancer within the past 5 years with exception of adequately treated localised basal cell carcinoma of the skin, in situ cervical carcinoma or solid malignancy surgically excised in toto without recurrence for five years
22. Women of child-bearing potential not protected by effective contraceptive method of birth control or surgical sterilization and/or who are unwilling or unable to be tested for pregnancy (Pregnancy status will be checked by serum pregnancy testing before initiation of study treatment and by urine pregnancy testing during the trial)
23. Known allergy or sensitivity to losartan or its excipients (microcrystalline cellulose [E460]; lactose monohydrate; pregelaatinized maize starch; magnesium stearate [E572]; hydroxypropyl cellulose [E463]; hypromellose [E464])

Previous exclusion criteria until 09/07/2012:
4. Haemoglobin A1C>9.0
14. Recent (within 3 months of baseline liver biopsy and screening visit) change in anti-diabetes treatment or change in dose or regimen, or introduction of Vitamin E or C, betaine, s-adenosyl methionine, ursodeoxycholic acid, silymarin, fibrate, pentoxifylline, orlistat, sibutramine or rimonabant.

Previous exclusion criteria:
4. Haemoglobin A1C >8.5
12. Recent (within 6 months of baseline liver biopsy and screening visit) or concomitant use of a

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Kleiner fibrosis score, based on histological fibrosis stage at trial entry and end of study (96 weeks)

Secondary Outcome Measures

Name	Time	Method
1. Measurement of change in fibroscan score performed at trial entry, 48 weeks and end of study <br>2. Serological (Enhanced Liver Fibrosis test [ELF™ test]) markers of fibrosis performed at trial entry, 48 weeks and end of study <br>3. Change in non-alcoholic fatty liver disease (NAFLD) activity score (NAS) from baseline, determined by liver biopsy at trial entry and end of study