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

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ClinicalTrials.gov Identifier: NCT01051219
Recruitment Status : Completed
First Posted : January 18, 2010
Last Update Posted : October 7, 2015
Sponsor:
Collaborator:
Newcastle University
Information provided by (Responsible Party):
Newcastle-upon-Tyne Hospitals NHS Trust

Tracking Information
First Submitted Date  ICMJE January 15, 2010
First Posted Date  ICMJE January 18, 2010
Last Update Posted Date October 7, 2015
Study Start Date  ICMJE May 2011
Actual Primary Completion Date November 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 15, 2010)
The primary outcome will be change in Kleiner fibrosis score, [Kleiner DE et al Hepatology 2005], based on histological fibrosis stage (as judged by two independent blinded histopathologists from liver biopsies), from pre-treatment to end-of-study [ Time Frame: trial entry, end of study (2 years) ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 15, 2010)
  • Change in radiological (fibroscan) and serological (ELF) markers of fibrosis [ Time Frame: trial entry, 48 weeks, 96 weeks ]
  • change in NAFLD activity score (NAS) [ Time Frame: trial entry, end of study ]
  • comparison of "responder rate" - placebo versus intervention [ Time Frame: trial entry, end of study ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Anti-Fibrotic Effects of Losartan In Nash Evaluation Study
Official Title  ICMJE A Randomised, Controlled Trial of Losartan as an Anti-fibrotic Agent in Non-alcoholic Steatohepatitis
Brief Summary

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:

  1. That the safety profile of the angiotensin receptor blocker (losartan) in this patient population is acceptable
  2. That losartan can prevent clinical deterioration in non-alcoholic fatty liver disease
  3. That serum, radiological and histological markers of fibrosis correlate in these patients over a 24 month period
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Nonalcoholic Steatohepatitis
Intervention  ICMJE Drug: Losartan
50 milligrams to be taken orally, daily
Other Name: Losartan also known as Cozaar
Study Arms  ICMJE
  • Active Comparator: Losartan, daily medication
    50 milligrams Losartan to be taken orally daily
    Intervention: Drug: Losartan
  • Placebo Comparator: Placebo
    A matched placebo will be given for patients to take once daily
    Intervention: Drug: Losartan
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 6, 2015)
45
Original Estimated Enrollment  ICMJE
 (submitted: January 15, 2010)
214
Actual Study Completion Date  ICMJE December 2014
Actual Primary Completion Date November 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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])
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01051219
Other Study ID Numbers  ICMJE EME-08/43/15
ISRCTN ( Registry Identifier: 57849521 )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Newcastle-upon-Tyne Hospitals NHS Trust
Study Sponsor  ICMJE Newcastle-upon-Tyne Hospitals NHS Trust
Collaborators  ICMJE Newcastle University
Investigators  ICMJE
Study Chair: Christopher P Day, PhD Newcastle University
Study Director: Derek Mann, PhD Newcastle University
Study Director: Stephen F Stewart, PhD Newcastle University
Study Director: Elaine McColl, PhD Newcastle University
Study Director: Ian N Steen, PhD Newcastle University
PRS Account Newcastle-upon-Tyne Hospitals NHS Trust
Verification Date October 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP