Double-blind Clinical Trial to Evaluate the Safety and Efficacy of Two Doses of Prolonged Release Pirfenidone, Compared Against Placebo Plus Conventional Therapy in Patients With Compensated Liver Cirrhosis.

ODISEA Study

This will be a multicenter, double-blind clinical trial to evaluate the safety and efficacy of two doses of prolonged release pirfenidone, compared against placebo plus conventional therapy in patients with compensated liver cirrhosis. The study will be conducted in compliance with International Standard good clinical practices (GCPs) and the Declaration of Helsinki. The protocol is approved by a local Institutional Review Board and registered in clinical trials.gov.

2015-06-26

2021-12-30

2023-03-24

Completed

Early phase I

180

Inclusion Criteria: 1. Both genders over 18 years of age. 2. Patients with clinical, biochemical, radiological diagnostic confirmation as well as evidence of grade 4 fibrosis based on an invasive (liver biopsy) or non-invasive method (fibrotest and/or fibroscan). 3. With functional class A (score of 5 and 6) and B (score of 7 or 8) on the Child-Pugh scale. 4. Optionally, transjugular liver biopsy with measurement of the portal system flow pressure gradient, in at least 20% of the population. 5. Be controlled with medications that are consumed at stable doses for at least 30 days. 6. Have a BMI greater than 19.1 kg/m 2 and less than 34.9 kg/m 2 7. Have the required standardized and homogeneous diet for patients 8. Do not drink alcoholic beverages for at least one year prior to the start of the study. 9. Electrocardiogram normal or without clinical significance. 10. Laboratory tests that confirm your condition and functional class, with results that, in the opinion of the principal investigator, do not put the patient at risk: 1. Complete blood count, with hemoglobin values ≥ 12 g/dL, leukocytes ≥ 3,500 mL, platelets ≥ 50,000 mL 2. Blood chemistry (glucose, urea, creatinine, uric acid, cystatin C). 3. Complete liver function tests (total protein, globulin, albumin, ALT, AST, gamma-glutamyltransferase (GGT), alkaline phosphatase (AP), lactic dehydrogenase (LDH), Total Bilirubin, C-reactive Protein). 4. Fibrotest and/or FibroScan with a result of F4. 5. General urine examination. 11. Inclusion Criteria for patients with hepatitis C virus liver damage. 1. Having been previously treated with standardized antiviral management 2. More than 12 months have passed since the end of antiviral treatment. 12. Inclusion Criteria for patients with liver damage of autoimmune etiology. a. Be under immunosuppressive treatment (steroid plus azathioprine) at a stable dose for at least 6 months at the beginning of the study. 13. Inclusion Criteria for patients with liver damage due to alcohol. 1. With alcohol inactivity for at least one year before the start of the study. Exclusion Criteria: 1. Pregnancy and breastfeeding. 2. History of known allergy or hypersensitivity to PFD. 3. Have liver cirrhosis with functional reserve B (score of 9) or functional reserve C (score of 10 or more) on the Child-Pugh scale. 11 (See annexes). 4. History of Upper Gastrointestinal Bleeding, Ascites, Hepatic Encephalopathy or any other complication due to previous Portal Hypertension. 5. Body Mass Index less than 19 kg/m 2 or greater than 35 kg/m 2 6. Hemoglobin values less than 12 g/dL. 7. Have participated in another clinical study in the 60 days prior to the start of this one. 8. Hospitalization within 30 days prior to the start of medication administration. 9. Concomitant systemic infection other than hepatitis C virus (HCV), including Respiratory Tract Infections , Urinary Tract Infections, human immunodeficiency virus (HIV), cellulitis, etc. 10. Current use (less than 1 month) of colchicine, ursodeoxycholic acid, silimarin, or s-adenosine methionine, or cytotoxic agent, cytokine modulator or receptor antagonist, daily sildenafil or fluvoxamine, theophylline or other methylxanthines, or alternative medicine. 11. Have clinical data of pulmonary fibrosis, heart, respiratory or kidney failure (serum creatinine \> 1.5 mg/dL). 12. Other medications that, in the opinion of the principal investigator, may interfere with the study. 13. Any other clinical condition that causes fibrosis other than liver fibrosis or a condition that, in the opinion of the principal investigator, could compromise the safety and well-being of the patient or put the conduct of the study at risk, such as hepatocellular carcinoma. Elimination criteria Any patient who presents a clinical finding compatible with decompensated cirrhosis (bleeding of variceal origin, clinical ascites, evident hepatic encephalopathy, hepatocellular carcinoma) or an adverse event or condition that, in the opinion of the principal investigator, warrants suspension of the patient's participation will be suspended from the study, but their data will be considered in the "intention to treat" analysis, when applicable. In the event that a serious adverse event occurs that, in the opinion of the principal investigator, warrants suspension of the patient's participation. In these cases, clinical and biochemical data will be considered in the intention-to-treat analysis, when applicable.

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2024-02-20