Primary Prevention Hepatocellular Carcinoma by Metformin

NCT02319200 | Terminated Phase 3 DMC

• 1 other identifier: P120138
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

Metformin treatment during 36 months could be associated with decreased risk of HCC occurrence and liver related death in patients with compensated HCV cirrhosis and insulinoresistance. This study is an ancillary of the observational study from the CIRVIR cohort in which more than 1200 patients with compensated HCV cirrhosis are currently included. participating centers : 26

Conditions

Hepatocellular Carcinoma; Hepatitis C, Chronic; Cirrhosis

Keywords

Chemoprevention; Decompensation of cirrhosis; Hepatocellular Carcinoma; Death; Efficacy; Safety

Outcome Measures

Primary Outcomes (1)

• rate of HCC occurrence and liver related-death or transplantation.

  at 6 months

Secondary Outcomes (1)

• occurrence of liver-related complications (Ascites , gastrointestinal bleeding, encephalopathy)

  at 6 months

Study Arms (2)

Metformin

EXPERIMENTAL

1000 mg (2x500 mg) at morning and 1000 mg (2x500 mg) at afternoon (2000 mg per day) Metformin daily during 36 months

Drug: Metformin

placebo tablet

PLACEBO COMPARATOR

2 tablets at morning and 2 tablets at afternoon 4 tablets per day

Drug: placebo tablet

Interventions

Metformin DRUG

1000 mg (2x500 mg) at morning and 1000 mg (2x500 mg) at afternoon (2000 mg per day) Metformin daily during 36 months

Also known as: Glucophage

Metformin

placebo tablet DRUG

4 tablets per day for 36 months

placebo tablet

Eligibility Criteria

• Age: 18 Years - 77 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age of 18 years or older
• Patients included in ANRS cohort CO12 CirVir
• No indication for liver transplantation at baseline
• Without co-infection with HIV or HBV
• Insulino-resistance: (HOMA ≥2), or Body mass index≥ 25 kg/m ² without diabetes, or untreated known diabetes with HbA1c \< 7 %
• No treatment with Metformin or other oral hypoglycemic containing metformin within 30 days before enrollment
• Available healthcare insurance
• Signed written informed consent.

You may not qualify if:

• Patient under guardianship or homeless
• Pregnant or breast-feeding women
• Patients with severe disease (excluding HCV liver disease) may threaten short-term life
• Cirrhosis with Child Pugh score\> 7
• An alcohol consumption, higher than 40g / day for men and 30g / day for women
• Type 1 diabetes
• Diabetes treated with metformin
• Diabetes not treated with metformin with HbA1c ≥ 7%
• Hypersensitivity / intolerance in biguanides
• Hypersensitivity to the active substance or to any of the excipients.
• Kidney failure defined by creatinine clearance less than 30 ml/ min (MDRD formula)

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• ANRS, Emerging Infectious Diseases: collaborator

Study Sites (1)

Roulot Dominique

Bobigny, 93009, France

Location

Related Publications (8)

• Nkontchou G, Cosson E, Aout M, Mahmoudi A, Bourcier V, Charif I, Ganne-Carrie N, Grando-Lemaire V, Vicaut E, Trinchet JC, Beaugrand M. Impact of metformin on the prognosis of cirrhosis induced by viral hepatitis C in diabetic patients. J Clin Endocrinol Metab. 2011 Aug;96(8):2601-8. doi: 10.1210/jc.2010-2415. Epub 2011 Jul 13.

  PMID: 21752887 BACKGROUND

• Sangiovanni A, Prati GM, Fasani P, Ronchi G, Romeo R, Manini M, Del Ninno E, Morabito A, Colombo M. The natural history of compensated cirrhosis due to hepatitis C virus: A 17-year cohort study of 214 patients. Hepatology. 2006 Jun;43(6):1303-10. doi: 10.1002/hep.21176.

  PMID: 16729298 BACKGROUND

• N'Kontchou G, Mahamoudi A, Aout M, Ganne-Carrie N, Grando V, Coderc E, Vicaut E, Trinchet JC, Sellier N, Beaugrand M, Seror O. Radiofrequency ablation of hepatocellular carcinoma: long-term results and prognostic factors in 235 Western patients with cirrhosis. Hepatology. 2009 Nov;50(5):1475-83. doi: 10.1002/hep.23181.

  PMID: 19731239 BACKGROUND

• Perseghin G, Calori G, Lattuada G, Ragogna F, Dugnani E, Garancini MP, Crosignani P, Villa M, Bosi E, Ruotolo G, Piemonti L. Insulin resistance/hyperinsulinemia and cancer mortality: the Cremona study at the 15th year of follow-up. Acta Diabetol. 2012 Dec;49(6):421-8. doi: 10.1007/s00592-011-0361-2. Epub 2012 Jan 4.

  PMID: 22215126 BACKGROUND

• Goodwin PJ, Ennis M, Pritchard KI, Trudeau ME, Koo J, Taylor SK, Hood N. Insulin- and obesity-related variables in early-stage breast cancer: correlations and time course of prognostic associations. J Clin Oncol. 2012 Jan 10;30(2):164-71. doi: 10.1200/JCO.2011.36.2723. Epub 2011 Dec 12.

  PMID: 22162568 BACKGROUND

• Nkontchou G, Bastard JP, Ziol M, Aout M, Cosson E, Ganne-Carrie N, Grando-Lemaire V, Roulot D, Capeau J, Trinchet JC, Vicaut E, Beaugrand M. Insulin resistance, serum leptin, and adiponectin levels and outcomes of viral hepatitis C cirrhosis. J Hepatol. 2010 Nov;53(5):827-33. doi: 10.1016/j.jhep.2010.04.035. Epub 2010 Jul 14.

  PMID: 20728234 BACKGROUND

• Salmon D, Bani-Sadr F, Loko MA, Stitou H, Gervais A, Durant J, Rosenthal E, Quertainmont Y, Barange K, Vittecoq D, Shoai-Tehrani M, Alvarez M, Winnock M, Trinchet JC, Dabis F, Sogni P. Insulin resistance is associated with a higher risk of hepatocellular carcinoma in cirrhotic HIV/HCV-co-infected patients: results from ANRS CO13 HEPAVIH. J Hepatol. 2012 Apr;56(4):862-8. doi: 10.1016/j.jhep.2011.11.009. Epub 2011 Dec 13.

  PMID: 22173166 BACKGROUND

• Svegliati-Baroni G, Faraci G, Fabris L, Saccomanno S, Cadamuro M, Pierantonelli I, Trozzi L, Bugianesi E, Guido M, Strazzabosco M, Benedetti A, Marchesini G. Insulin resistance and necroinflammation drives ductular reaction and epithelial-mesenchymal transition in chronic hepatitis C. Gut. 2011 Jan;60(1):108-15. doi: 10.1136/gut.2010.219741. Epub 2010 Oct 21.

  PMID: 20966027 BACKGROUND

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Hepatitis C, Chronic; Fibrosis; Death

Interventions

Metformin

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases; Hepatitis C; Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis, Chronic; Hepatitis; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• Dominique Roulot, MD

  Hospital Avicenne

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 13, 2014
• First Posted: December 18, 2014
• Study Start: June 1, 2015
• Primary Completion: April 1, 2016
• Study Completion: April 1, 2016
• Last Updated: January 11, 2017

Record last verified: 2017-01

Locations

FR (1)