Anti-Fibrotic Effects of Losartan In Nash Evaluation Study (FELINE)

Newcastle-upon-Tyne Hospitals NHS Trust

Status and phase

Completed

Phase 3

Conditions

Nonalcoholic Steatohepatitis

Treatments

Drug: Losartan

Study type

Interventional

Funder types

Other

Identifiers

NCT01051219

ISRCTN (Registry Identifier)

EME-08/43/15

Details and patient eligibility

About

This is a randomized, controlled trial to determine whether Losartan is effective at slowing down, halting or reversing liver fibrosis in patients with non-alcoholic steatohepatitis (NASH). Liver fibrosis is the accumulation of tough, fibrous scar tissue in the liver which occurs in patients with NASH. NASH resembles alcoholic liver disease, but occurs in people who drink little or no alcohol. The major feature in NASH is fat in the liver, along with inflammation and damage, which may lead to cirrhosis, in which the liver is permanently damaged and scarred and no longer able to function properly.

Primary hypothesis:

That losartan is superior to placebo in reversing, slowing down or halting fibrosis in patients with non-alcoholic fatty liver disease, after 24 months of treatment.

Secondary hypothesis:

That the safety profile of the angiotensin receptor blocker (losartan) in this patient population is acceptable
That losartan can prevent clinical deterioration in non-alcoholic fatty liver disease
That serum, radiological and histological markers of fibrosis correlate in these patients over a 24 month period

Enrollment

45 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Adults (both males and females, aged 18+) with steatohepatitis and fibrosis (Kleiner F1-F3), resulting from non-alcoholic fatty liver disease.

Exclusion criteria

Refusal or inability (lack of capacity) to give informed consent
Average alcohol ingestion >21 units/week (males) or >14 units/week (females)
History or presence of Type 1 diabetes mellitus
Haemoglobin A1C >15.0
Other causes of chronic liver disease or hepatic steatosis
Any contra-indication to liver biopsy
History of, or planned, gastrointestinal bypass surgery
Hepatocellular carcinoma
Previous liver transplantation
Recent significant weight loss (>5% total body weight within last 6 months)
Electrolyte disturbance: potassium level outside the normal (local) range
Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >10 x upper limit of normal (ULN) at screening
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
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
Intolerance of angiotensin receptor blockers (ARBs) or presence of multiple allergic reactions to drugs
Use of angiotensin-converting enzyme (ACE) inhibitor or ARB in previous year
Hypotension (systolic <100, diastolic <60)
Renal failure (Cr >130)
Participation in any clinical study of an investigational agent within 30 days or five half-lives of the investigational product, whichever is longer
Presence of clinically relevant cardiovascular, pulmonary, gastrointestinal, 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
Presence or history of cancer within the past 5 years with exception of adequately treated localized basal cell carcinoma of the skin, in situ cervical carcinoma or solid malignancy surgically excised in toto without recurrence for five years
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)
Known allergy or sensitivity to losartan or its excipients (microcrystalline cellulose [E460]; lactose monohydrate; pregelitanized maize starch; magnesium stearate [E572]; hydroxypropyl cellulose [E463]; hypromellose [E464])