Pirfenidone and Advanced Liver Fibrosis.

NCT04099407 | Completed Phase 2

• 1 other identifier: PROMETEO Study
• Study Type: interventional
• Target: 122
• Locations: 1 country
• Sites: 1

Brief Summary

Pirfenidone (PFD), an oral antifibrotic drug with anti-inflammatory and anti-oxidant properties, has been granted marketing authorization by the European Medicine Agency and FDA, for the treatment of idiopathic pulmonary fibrosis (IPF). However, few studies have focused on its clinical utilization in patients with advanced hepatic fibrosis. Therefore, Investigators aim to evaluate a prolonged-release PFD formulation (PR-PFD) plus standard of care management on disease progression in patients with advanced liver fibrosis (ALF). Methods: Patients with diverse chronic liver disease etiology (alcohol-related, hepatitis B or C, autoimmune or fatty liver disease) will be screened with two non invasive liver fibrosis methods (Fibroscan®) and Fibro Test®) and those with ALF (F3 or F4) will be treated for at least 12 months with PR-PFD. Antifibrotic effects Will be assessed at 6 and 12 months; variations greater than 30% in estimated fibrosis scores or 1 point on the METAVIR scale will be considered clinically significant. PFD plasma levels, serum endothelin-1, IL6, TNFα and TGFβ1, Quality of life and fatigue scales will be evaluated. Parametric and non parametric statistics will be utilized and p values lower tan 5% will be considered clinically significant.

Conditions

Liver Fibrosis; Chronic Liver Disease

Keywords

Liver fibrosis; Fibrosis treatment; Fibrosis reversibility; Pirfenidone

Outcome Measures

Primary Outcomes (4)

• Fibrosis reversal based on Fibrotest

  Reduction of fibrosis score by at least 30% in Fibrotest units.

  12 months

• Fibrosis reversal based on Hepatic Elastography

  Reduction of fibrosis score by at least 30% in kilo Pascals (kPa) according to accurate hepatic elastography measurements.

  12 months

• Fibrosis reversal based on METAVIR

  Reduction of fibrosis score by at least one point on the METAVIR fibrosis scale.

  12 months

• Safety endpoint based on clinical side effects

  Clinical side effects wiil be evaluated according to World Health Organization grade modified toxicity scale.

  12 months

Secondary Outcomes (4)

• Improvement in Quality of life

  12 months

• Improvement in Liver function values: bilirubin

  12 months

• Improvement in Liver function values:albumin

  12 months

• Improvement in fibrosis molecular marker

  12 months

Study Arms (1)

Antifibrotic plus standard of care treatment

EXPERIMENTAL

Prolonged release pirfenidone formulation in combination with standard of care treatment.

Drug: Pirfenidone; Other: Standard of care

Interventions

Pirfenidone DRUG

Treatment consist of 600 mg tablets of a prolonged-released formulation of Pirfenidone. Patients are instructed to take medication orally, every 12 h, after breakfast and dinner.

Antifibrotic plus standard of care treatment

Standard of care OTHER

All participants will require to adhere to a standard of care including nutritional support, quarterly medical evaluation to review lab results and adjust medications, bi-annual Fibrotest, FibroScan and liver ultrasound, and annual upper-gastrointestinal endoscopy.

Antifibrotic plus standard of care treatment

Eligibility Criteria

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

You may qualify if:

• Patients with chronic liver disease whose fibrosis continued to progress despite abstaining from alcohol (ALD), achieving sustained virologic response (VHC), or otherwise maintaining stable disease (NAFLD, AIH)..
• Advanced liver fibrosis defined as fibrosis grade 3 or grade 4 according to METAVIR scale based in two non-invasive liver fibrosis evaluation methods (FibroScan and Fibrotest).
• Stable liver disease.

You may not qualify if:

• Patients with mild fibrosis (F1-F2)
• Under medication with colchicine, silymarin, non-steroidal anti-inflammatory drugs, and any hepatotoxic drug.
• Decompensation based on a history of hepatic encephalopathy, esophageal variceal bleeding, or ascites in the previous 6 months
• HIV, Hepatitis B virus (HBV) or any active infectious processes not of a self-limited nature.
• Concomitant or prior history of malignancy other than curatively-treated skin cancer or surgically-cured in situ carcinoma of the cervix.
• Hemoglobinopathy or any disease associated with hemolysis.
• History of significant cardiac or pulmonary disease that could be exacerbated by anemia.
• Liver masses detected by baseline scanner or Alpha-fetoprotein \>100 ng/L.
• Pregnancy.
• Alcohol or intravenous drug abuse within the previous year.

Sponsors & Collaborators

• Grupo Mexicano para el Estudios de las Enfermedades Hepaticas: lead

Study Sites (1)

Liver Clinic 1

Mexico City, Mexico

Location

Related Publications (1)

• Poo JL, Torre A, Aguilar-Ramirez JR, Cruz M, Mejia-Cuan L, Cerda E, Velazquez A, Patino A, Ramirez-Castillo C, Cisneros L, Bosques-Padilla F, Hernandez L, Gasca F, Flores-Murrieta F, Trevino S, Tapia G, Armendariz-Borunda J, Munoz-Espinosa LE. Benefits of prolonged-release pirfenidone plus standard of care treatment in patients with advanced liver fibrosis: PROMETEO study. Hepatol Int. 2020 Sep;14(5):817-827. doi: 10.1007/s12072-020-10069-3. Epub 2020 Aug 19.

  PMID: 32813194 DERIVED

MeSH Terms

Conditions

Liver Cirrhosis

Interventions

pirfenidone; Standard of Care

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigador, Head of Liver Clinic

Model Details: This will be a real-life, multicenter, open-label, proof of concept trial to determine the safety and efficacy of 12 months of treatment with PR-PFD in combination with standard of care treatment

Study Record Dates

• First Submitted: September 17, 2019
• First Posted: September 23, 2019
• Study Start: August 1, 2019
• Primary Completion: August 31, 2020
• Study Completion: December 31, 2020
• Last Updated: April 2, 2024

Record last verified: 2024-04

Locations

ME (1)