Safety and Efficacy Study of Pirfenidone to Treat Idiopathic Pulmonary Fibrosis(IPF)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified February 2012 by Beijing Kawin Technology Share-Holding Co., Ltd..
Recruitment status was  Recruiting
Sponsor:
Information provided by (Responsible Party):
Zuojun Xu, Beijing Kawin Technology Share-Holding Co., Ltd.
ClinicalTrials.gov Identifier:
NCT01504334
First received: December 30, 2011
Last updated: February 5, 2012
Last verified: February 2012
  Purpose

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive form of lung disease characterized by fibrosis of the supporting framework (interstitium) of the lungs. By definition, the term is used only when the cause of the pulmonary fibrosis is unknown ("idiopathic"). Microscopically, lung tissue from patients shows a characteristic set of histologic/pathologic features known as usual interstitial pneumonia (UIP). UIP is therefore the pathologic counterpart of IPF.Idiopathic pulmonary fibrosis is characterized by radiographically evident interstitial infiltrates predominantly affecting the lung bases and by progressive dyspnea and worsening of pulmonary function. No therapy has been clearly shown to prolong survival. The current strict definition of idiopathic pulmonary fibrosis provides a new focus for basic and clinical research that will improve insight into the pathogenesis of this disorder and stimulate the development of novel therapies.

Pirfenidone has proven antifibrotic and anti-inflammatory properties in various in vitro systems and animal models of pulmonary fibrosis, although its precise mechanism of action remains unclear. It attenuates fibroblast proliferation, production of fibrosis-associated proteins and cytokines, and the increased biosynthesis and accumulation of extracellular matrix in response to cytokines such as transforming growth factor-β. It is also shown to slow tumor cell proliferation by inhibiting fibroblast growth factor, epidermal growth factor and platelet-derived growth factor.

Pirfenidone has not been widely approved for clinical use in China, in this study, safety and efficacy were evaluated to see if pirfenidone has a significant advantage over placebo in terms of improving lung function and life quality etc. (see primary and secondary criteria) or slows down the deterioration of lung function in Chinese subjects diagnosed with IPF.


Condition Intervention Phase
Idiopathic Pulmonary Fibrosis
Drug: Pirfenidone
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multicenter, Randomized, Double-blind, Placebo-controlled Trial for the Safety and Efficacy of Pirfenidone in the Treatment of Idiopathic Pulmonary Fibrosis (IPF)

Resource links provided by NLM:


Further study details as provided by Beijing Kawin Technology Share-Holding Co., Ltd.:

Primary Outcome Measures:
  • Changes in forced vital capacity (FVC) [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
    Changes in FVC from 48 weeks to baseline


Secondary Outcome Measures:
  • Changes in lung function (including arterial blood gas analysis) [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
    Lung function will be assessed as improved/stabilized/exacerbated from 48 weeks to baseline.

  • Acute Exacerbation during the whole treatment procedure(frequency and severity) [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]

    The following clinical deterioration symptoms within a month that cannot be explained by other reasons will be assessed as acute exacerbation:

    1. Aggravated dyspnea;
    2. Newly discovered chest interstitial lung abnormality by radiograph/HRCT, without pneumothorax or pleural effusion;
    3. PaO2 decreases ≥10mm Hg,heart failure or pulmonary embolism excluded.

    Acute Exacerbation can be assessed if 1 and 2 appear or 1 and 3 appear.


  • Progression-free time [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]

    Progression of disease during the whole study period is defined as follows:

    1. Progressive dyspnea (objective evaluation);
    2. FVC absolute value progressively and constantly decreases compared with baseline value;
    3. DLCO absolute value (after hemoglobin calibration) progressively and constantly decreases compared with baseline value;
    4. Fibrosis progressive deterioration by HRCT examination;
    5. Acute Exacerbation;
    6. Death caused by respiratory failure.

  • 6 Minute Walk Test (6MWT ): Changes in 6 minute walk distance (6MWD) and SpO2 from 48 weeks to baseline [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
    Method: The walking test is conducted in a corridor 33 meters long. The patient is instructed to "walk from end to end, covering as much ground as they can in the allotted time". The total distance ambulated in meters during the 6-minute walk test and the number of rest stops is recorded. 6MWD, weight, heart rate, BP, SpO2, and a self-reported rating of perceived exertion [modified Borg RPE scale rating (0 to 10 scale)] is recorded after the walk.

  • Borg RPE scale rating improvement rate during the whole study period [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
    Patient percentage whose Borg RPE scale rating improves more than 1 level.

  • Lung interstitial change observed by HRCT [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
    Changes in HRCT lung interstitial evaluation score from 48 weeks to baseline

  • Life quality: assessed by St. George respiratory questionnaire (SGRQ). [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
    Life quality will be assessed as improved if SGRQ single or total score increased >4% when completing the trial; Life quality will be assessed as stabilized if SGRQ single or total score changes within the range of 4% when completing the trial; Life quality will be assessed as exacerbated if SGRQ single or total score decreased >4% when completing the trial.


Estimated Enrollment: 80
Study Start Date: January 2012
Estimated Study Completion Date: March 2013
Estimated Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pirfenidone(200mg)
Pirfenidone(200mg)tablets will be taken 3 times a day during the whole study process. For the first week, 1 tablet will be taken each time. For the second week, 2 tablets will be taken each time. From the third week to the 48th week, 3 tablets will be taken each time. Base drug Acetyl Cysteine Tablets(600mg)will be taken once a day, 1 tablet each time from the first to the 48th week.
Drug: Pirfenidone
Pirfenidone(200mg)tablets will be taken 3 times a day during the whole study process. For the first week, 1 tablet will be taken each time. For the second week, 2 tablets will be taken each time. From the third week to the 48th week, 3 tablets will be taken each time. Base drug Acetyl Cysteine Tablets(600mg)will be taken once a day, 1 tablet each time from the first to the 48th week.
Placebo Comparator: Placebo (without active ingredient) Drug: Placebo
Placebo(without active ingredient) tablets will be taken 3 times a day during the whole study process. For the first week, 1 tablet will be taken each time. For the second week, 2 tablets will be taken each time. From the third week to the 48th week, 3 tablets will be taken each time. Base drug Acetyl Cysteine Tablets(600mg)will be taken once a day, 1 tablet each time from the first to the 48th week for both groups.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Written informed consent signed;
  2. 18-75 years of age;
  3. Clinically or multidisciplinarily diagnosed idiopathic pulmonary fibrosis(see 2011 guidance );
  4. Resting state PaO2≥50mg, FVC%≥45% normal predicted value and DLCO≥30% normal predicted value.

Exclusion Criteria:

  1. Allergic to pirfenidone;
  2. Dyspnea symptoms relieved in the past 6 months;
  3. Patients in acute exacerbation phase;
  4. Diabetic patients whose fasting venous glucose >11.1 mmol/L;
  5. Patients with malignant tumor and hemorrhagic diseases;
  6. Patients with serious underlying pulmonary disease;
  7. Patients with serious heart disease(NYHA class Ⅲ-Ⅳ), liver disease(ALT or AST 2 times above the upper level of normal value range), kidney disease(Cr above the upper level of normal value range);
  8. Patients who has taken Acetylcysteine in the past 3 months;
  9. Patients who has taken Prednisone>15mg/day(or other equivalent amount of glucocorticoid) and/or Immunosuppresants in the past 3 months;
  10. Patients who has taken interferon, penicillamine, colchine or other agents for the treatment of IPF;
  11. Pregnant or lactating women;
  12. Participated in other clinical trials in the past 1 month;
  13. The investigator assessed as inappropriate to participate in this clinical trial.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01504334

Contacts
Contact: Xu Zuojun, MD +86-10-65295039 xuzj@hotmail.com

Locations
China, Beijng
Peking Union Medical College Hospital Recruiting
Beijing, Beijng, China, 100032
Contact: Zuojun Xu, MD    010-65295039    xuzj@hotmail.com   
Principal Investigator: Zuojun Xu, MD         
Sponsors and Collaborators
Beijing Kawin Technology Share-Holding Co., Ltd.
Investigators
Principal Investigator: Xu Zuojun, MD Peking Union Medical College Hospital
  More Information

No publications provided

Responsible Party: Zuojun Xu, Chief Physician, Beijing Kawin Technology Share-Holding Co., Ltd.
ClinicalTrials.gov Identifier: NCT01504334     History of Changes
Other Study ID Numbers: KAWIN-001
Study First Received: December 30, 2011
Last Updated: February 5, 2012
Health Authority: China: Food and Drug Administration

Additional relevant MeSH terms:
Fibrosis
Pulmonary Fibrosis
Idiopathic Pulmonary Fibrosis
Pathologic Processes
Lung Diseases
Respiratory Tract Diseases
Idiopathic Interstitial Pneumonias
Lung Diseases, Interstitial
Acetylcysteine
Pirfenidone
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Expectorants
Respiratory System Agents
Free Radical Scavengers
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Central Nervous System Agents
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Anti-Inflammatory Agents
Antirheumatic Agents
Antineoplastic Agents

ClinicalTrials.gov processed this record on July 24, 2014