Pirfenidone in Progressive Interstitial Lung Disease Associated With Clinically Amyopathic Dermatomyositis

Randomized Controlled Trial of Pirfenidone in Patients With Progressive Interstitial Lung Disease Associated With Clinically Amyopathic Dermatomyositis

Interstitial lung disease (ILD) is a common complication of dermatomyositis (DM) with prevalence up to 65%, and is considered to be one of the determining factors of prognosis. Clinical amyopathic dermatomyositis (CADM), which is a special phenotype of DM, with characteristic cutaneous manifestations but no or only subclinical myopathy. Many studies, mainly from Asia, including ours, have demonstrated that these patients with CADM tend to develop a rapidly progressive ILD (RPILD) and have a poor response to conventional therapy, such as high-dose corticosteroids and immunosuppressants, leading to lethal outcome with a 6-month survival rate of less than 50%.

Pirfenidone, a new oral antifibrotic agent, has been approved for the treatment of idiopathic pulmonary fibrosis (IPF). Randomized controlled trials of pirfenidone in patients with IPF suggested that it could ameliorate pulmonary function decline and improve the progression-free survival. Its utility in connective tissue disease (CTD) related ILD has been implicated, but no evidence has yet demonstrated its efficacy. Therefore, the investigators conduct this study to evaluate the possible therapeutic effects of pirfenidone on RPILD associated with CADM.

Study Overview

• Status: Unknown
• Conditions: Interstitial Lung Disease; Dermatopolymyositis
• Intervention / Treatment: Drug: Pirfenidone

• Study Type: Interventional
• Enrollment (Anticipated): 57
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Zhiwei Chen, MS; Phone Number: +8613621621736; Email: zwchen88@gmail.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200001
      • Department of Rheumatology, Ren Ji Hospital South Campus, School of Medicine, Shanghai JiaoTong University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Willingness of the subject to participate in the study, proven by signing the informed consent;
• All participants fulfilled the provisional diagnosis of CADM according to the modified Sontheimer's criteria.
• The course of ILD is longer than 3 months, but shorter than 6 months, presenting as increase in level of dyspnea, and worsening of fibrosis on pulmonary HRCT with >10% increase of HRCT score, and/or decrease in %FVC by >10% absolute value.

Exclusion Criteria:

• Participants who are unwilling to sign the inform consent;
• The course of participants ever treated with biologics including basiliximab, or malignancy-associated CADM or overlapped with other CTD, or with alanine transaminase more than 2 times the upper normal limits;
• Pregnancy or lactation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: pirfenidone; Eligible participants for clinical trial were randomized in a 2:1 ratio to pirfenidone/blank add-on. Pirfenidone was administered in three divided doses (200mg tid), and increased to the manufacturer's instructed target dose (600mg tid) over a 2-week period. Investigators were allowed to adjust the dose according to the participants' tolerance.	Drug: Pirfenidone; Pirfenidone was administered in three divided doses (200mg tid), and increased to the manufacturer's instructed target dose (600mg tid) over a 2-week period. The maximum dose was maintained throughout the study in patients who tolerated it.
NO_INTERVENTION: Blank; Eligible participants for clinical trial were randomized in a 2:1 ratio to pirfenidone/blank add-on.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
changes of 12-month survival from the onset of ILD	the effect of pirfenidone on improving the survival rate	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
changes of high-resolution computed tomography (HRCT) scores from baseline at each visit	the influence of pirfenidone on pulmonary interstitial changes	one year
changes of pulmonary function test from baseline at each visit	the influence of pirfenidone on pulmonary function changes	one year

Collaborators and Investigators

• Sponsor: RenJi Hospital

Study record dates

Study Major Dates

• Study Start: July 1, 2016
• Primary Completion (ANTICIPATED): June 1, 2017
• Study Completion (ANTICIPATED): June 1, 2018

Study Registration Dates

• First Submitted: June 21, 2016
• First Submitted That Met QC Criteria: June 30, 2016
• First Posted (ESTIMATE): July 1, 2016

Study Record Updates

• Last Update Posted (ESTIMATE): July 1, 2016
• Last Update Submitted That Met QC Criteria: June 30, 2016
• Last Verified: June 1, 2016

More Information

Terms related to this study

• Keywords: Pirfenidone; Interstitial lung disease; Dermatopolymyositis
• Additional Relevant MeSH Terms: Nervous System Diseases; Skin Diseases; Respiratory Tract Diseases; Musculoskeletal Diseases; Connective Tissue Diseases; Muscular Diseases; Neuromuscular Diseases; Polymyositis; Myositis; Lung Diseases; Lung Diseases, Interstitial; Dermatomyositis; Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Pirfenidone
• Other Study ID Numbers: RenJi-ADM

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED