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Pirfenidone and Advanced Liver Fibrosis. (PROMETEO)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT04099407
Recruitment Status : Recruiting
First Posted : September 23, 2019
Last Update Posted : September 23, 2019
Information provided by (Responsible Party):
Jorge L Poo, Grupo Mexicano para el Estudios de las Enfermedades Hepaticas

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.

Condition or disease Intervention/treatment Phase
Liver Fibrosis Chronic Liver Disease Drug: Pirfenidone Other: Standard of care Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: 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
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pirfenidone in Combination With Standard of Care Treatment in Patients With Advanced Liver Fibrosis. Multicenter, Open Trial Focused on Safety, Fibrosis Efficacy Evaluation, and Pharmacokinetic Data.
Actual Study Start Date : August 1, 2019
Estimated Primary Completion Date : August 31, 2020
Estimated Study Completion Date : December 31, 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Pirfenidone

Arm Intervention/treatment
Experimental: Antifibrotic plus standard of care treatment
Prolonged release pirfenidone formulation in combination with standard of care treatment.
Drug: Pirfenidone
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.

Other: Standard of care
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.

Primary Outcome Measures :
  1. Fibrosis reversal based on Fibrotest [ Time Frame: 12 months ]
    Reduction of fibrosis score by at least 30% in Fibrotest units.

  2. Fibrosis reversal based on Hepatic Elastography [ Time Frame: 12 months ]
    Reduction of fibrosis score by at least 30% in kilo Pascals (kPa) according to accurate hepatic elastography measurements.

  3. Fibrosis reversal based on METAVIR [ Time Frame: 12 months ]
    Reduction of fibrosis score by at least one point on the METAVIR fibrosis scale.

  4. Safety endpoint based on clinical side effects [ Time Frame: 12 months ]
    Clinical side effects wiil be evaluated according to World Health Organization grade modified toxicity scale.

Secondary Outcome Measures :
  1. Improvement in Quality of life [ Time Frame: 12 months ]
    Quality of life will be evaluated according to nonutility-based Short Form-36 survey.

  2. Improvement in Liver function values: bilirubin [ Time Frame: 12 months ]
    Improvement by at least 30% in serum Bilirubin levels (mg/dL)

  3. Improvement in Liver function values:albumin [ Time Frame: 12 months ]
    Improvement by at least 30% in serum albumin levels (mg/dL)

  4. Improvement in fibrosis molecular marker [ Time Frame: 12 months ]
    Improvement in serum concentrations of transforming growth factor beta (TGF-β1), quantified by ELISA in an automated enzyme-linked immunosorbent assay (EIA) analyzer.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. 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)..
  2. 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).
  3. Stable liver disease.

Exclusion Criteria:

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT04099407

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Contact: Jorge L Poo, MD 525556668304
Contact: Javier Lizardi, MD 525556668305

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Liver Clinic 1 Recruiting
Mexico City, Mexico
Contact: Jorge L Poo, MD    525556668304 ext 525556668304   
Contact: Javier Lizardi, MD    525556668305   
Sponsors and Collaborators
Grupo Mexicano para el Estudios de las Enfermedades Hepaticas
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Responsible Party: Jorge L Poo, Principal Investigador, Head of Liver Clinic, Grupo Mexicano para el Estudios de las Enfermedades Hepaticas Identifier: NCT04099407    
Other Study ID Numbers: PROMHEPA
First Posted: September 23, 2019    Key Record Dates
Last Update Posted: September 23, 2019
Last Verified: September 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Jorge L Poo, Grupo Mexicano para el Estudios de las Enfermedades Hepaticas:
Liver fibrosis
Fibrosis treatment
Fibrosis reversibility
Additional relevant MeSH terms:
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Liver Diseases
Liver Cirrhosis
Pathologic Processes
Digestive System Diseases
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Anti-Inflammatory Agents
Antirheumatic Agents
Antineoplastic Agents