Clinical trial NCT01504334: Safety and Efficacy Study of Pirfenidone to Treat Idiopathic Pulmonary Fibrosis(IPF)
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)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Idiopathic Pulmonary Fibrosis
Lead sponsor: Beijing Kawin Technology Share-Holding Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2012-01-05
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility 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.

Primary outcomes:
measure: Changes in forced vital capacity (FVC)
timeFrame: 48 weeks
Secondary outcomes:
measure: Changes in lung function (including arterial blood gas analysis)
timeFrame: 48 weeks
measure: Acute Exacerbation during the whole treatment procedure（frequency and severity）
timeFrame: 48 weeks
measure: Progression-free time
timeFrame: 48 weeks
measure: 6 Minute Walk Test (6MWT )： Changes in 6 minute walk distance (6MWD) and SpO2 from 48 weeks to baseline
timeFrame: 48 weeks
measure: Borg RPE scale rating improvement rate during the whole study period
timeFrame: 48 weeks
measure: Lung interstitial change observed by HRCT
timeFrame: 48 weeks
measure: Life quality: assessed by St. George respiratory questionnaire (SGRQ).
timeFrame: 48 weeks
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking Union Medical College Hospital
state: Beijng
Study officials:
affiliation: Peking Union Medical College Hospital
name: Xu Zuojun, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Huang H, Dai HP, Kang J, Chen BY, Sun TY, Xu ZJ. Double-Blind Randomized Trial of Pirfenidone in Chinese Idiopathic Pulmonary Fibrosis Patients. Medicine (Baltimore). 2015 Oct;94(42):e1600. doi: 10.1097/MD.0000000000001600.