Pirfenidone vs. Nintedanib for Fibrotic Lung Disease After Coronavirus Disease-19 Pneumonia

A Study of the Efficacy and Safety of Pirfenidone vs. Nintedanib in the Treatment of Fibrotic Lung Disease After Coronavirus Disease-19 Pneumonia

Sponsors

Lead Sponsor: Postgraduate Institute of Medical Education and Research

Source Postgraduate Institute of Medical Education and Research
Brief Summary

The antifibrotic agents, namely pirfenidone and nintedanib have been found to be effective in the treatment of idiopathic pulmonary fibrosis (IPF). Nintedanib has also been found to be effective in treating systemic sclerosis-related interstitial lung disease (ILD) and non-IPF progressive fibrosing ILDs. Pirfenidone has also been found beneficial unclassifiable ILDs. Whether these drugs would be effective in treating post-COVID lung fibrosis also is unknown. As the final pathway of lung fibrosis appears to be common among different diffuse parenchymal lung diseases (DPLDs), it is hoped that these antifibrotic agents might be helpful in post-COVID fibrosis. There are no randomized studies that have assessed the role of pirfenidone or nintedanib in post COVID fibrosis. In the current study, we aim to assess the efficacy and safety of pirfenidone and compare it with nintedanib in the treatment of post-COVID lung fibrosis.

Detailed Description

Since the early part of 2020, the entire world has been affected by a pandemic of the coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The disease has a short incubation period (median, 3 days) and is highly transmissible. This disease may manifest as an asymptomatic infection and through an entire range of symptoms of varying severity to severe, life-threatening disease. Although diverse systemic features might be present, the usual presentation is with lower respiratory tract involvement in the form of pneumonia often resulting in the development of the acute respiratory distress syndrome (ARDS). In some patients, multi-organ failure sets in, possibly as a result of a cytokine storm interplaying with a thrombotic microangiopathy. Early lung disease is characterized pathologically by neutrophilic and exudative capillaritis in the lungs with some evidence of microthrombosis.2 This may be followed by a picture of diffuse alveolar damage along with ongoing intravascular thrombosis in the pulmonary vessels. In late stages, an organizing pneumonia (OP) develops with extensive proliferation of fibroblasts within the airspaces. Clinically, most patients make a complete recovery after COVID pneumonia. Other patients may demonstrate some signs of recovery from the acute illness with resolution of fever and recovery of organ functions, however they continue to have some degree of breathlessness, persistent infiltrates on radiologic studies, and/or hypoxemia. The CT abnormalities in these patients are commonly characterized by patchy, multifocal consolidation and ground-glass opacities suggestive of the OP pattern. Coarse reticulation and parenchymal bands may also be present. Patients with such diffuse lung disease after COVID-19, herein referred to as post-COVID diffuse lung disease (PC-DLD) are often treated with glucocorticoids. Although most patients with a predominant OP pattern of injury would have a resolution of lung parenchymal abnormalities either spontaneously or with glucocorticoids, some of them might develop signs of lung fibrosis, in the form of traction bronchiectasis and/or honeycombing. Some subjects have ongoing respiratory symptoms despite treatment with steroids, and they may be found to have persistent reticulation or non-resolving consolidation on chest imaging that may represent early fibrosis. The antifibrotic agents, namely pirfenidone and nintedanib have been found to be effective in the treatment of idiopathic pulmonary fibrosis (IPF). Nintedanib has also been found to be effective in treating systemic sclerosis-related interstitial lung disease (ILD) and non-IPF progressive fibrosing ILDs. Pirfenidone has also been found beneficial unclassifiable ILDs. Whether these drugs would be effective in treating post-COVID lung fibrosis also is unknown. As the final pathway of lung fibrosis appears to be common among different diffuse parenchymal lung diseases (DPLDs), it is hoped that these antifibrotic agents might be helpful in post-COVID fibrosis. There are no randomized studies that have assessed the role of pirfenidone or nintedanib in post COVID fibrosis. In the current study, we aim to assess the efficacy and safety of pirfenidone and compare it with nintedanib in the treatment of post-COVID lung fibrosis.

Overall Status Recruiting
Start Date 2021-03-17
Completion Date 2021-12-31
Primary Completion Date 2021-12-31
Phase Phase 4
Study Type Interventional
Primary Outcome
Measure Time Frame
Change in the forced vital capacity (FVC) 24 weeks
Secondary Outcome
Measure Time Frame
Proportion of subjects with improvement or stabilization 24 weeks
Proportion of subjects with a good composite response 24 weeks
Change in dyspnea score on modified Medical Research Council scale 24 weeks
Severity of dyspnea on the Functional Assessment of Chronic Illness Therapy - Dyspnea-10 item scale 24 weeks
Change in resting oxygen saturation 24 weeks
Proportion of subjects with oxygen desaturation on exercise testing 24 weeks
Percentage change in the six-minute walk distance 24 weeks
Proportion of participants who need rescue treatment 24 weeks
Change in health-related quality of life using the Short Form-36 questionnaire 24 weeks
Change in respiratory health status using the King's Brief ILD questionnaire 24 weeks
Changes in HRCT scores using the modified Salisbury system 24 weeks
Proportion of subjects who develop adverse effects due to either study drug 24 weeks
Predictors of response to antifibrotic agents, pirfenidone and nintedanib 24 weeks
Enrollment 48
Condition
Intervention

Intervention Type: Drug

Intervention Name: Pirfenidone

Description: Same as arm description

Arm Group Label: Pirfenidone

Intervention Type: Drug

Intervention Name: Nintedanib

Description: Same as arm description

Arm Group Label: Nintedanib

Eligibility

Criteria:

Inclusion Criteria: 1. Age above 18 years 2. Diagnosed to have COVID-19 by means of a real-time reverse transcription polymerase chain reaction (rRT-PCR) test performed on a respiratory (upper or lower respiratory) sample or positive IgM antibody test or a rapid antigen test with consistent clinicoradiologic findings within the previous 4 months 3. Persistent respiratory symptoms 4. Having post-COVID parenchymal involvement >10% of the lung parenchyma on visual inspection of the scans with the presence of radiologic signs of fibrosis (traction bronchiectasis/traction bronchiolectasis or honeycombing or reduced lung volumes), or having persistent reticulation or persistent consolidation despite a trial of glucocorticoids (minimum prednisolone dose of 10 mg/day, or equivalent) for a minimum period of 4 weeks after discharge for the acute COVID-19 illness Exclusion Criteria: 1. Pregnant or lactating women 2. Having absolute contraindication for pirfenidone or nintedanib (advanced liver cirrhosis, persistent elevation of liver transaminases, documented hypersensitivity to pirfenidone or nintedanib, receiving anticoagulants or high dose aspirin or having a vascular stent in situ) 3. Known patient with diffuse lung disease prior to the diagnosis of COVID

Gender:

All

Minimum Age:

18 Years

Maximum Age:

N/A

Healthy Volunteers:

No

Overall Contact

Last Name: Sahajal Dhooria, MD, DM

Phone: +919530661388

Email: [email protected]

Location
Facility: Status: Contact: Postgraduate Institute of Medical Education and Research Ritesh Agarwal, MD, DM +911722756825 [email protected]
Location Countries

India

Verification Date

2021-04-01

Responsible Party

Type: Principal Investigator

Investigator Affiliation: Postgraduate Institute of Medical Education and Research

Investigator Full Name: Sahajal Dhooria

Investigator Title: Assistant Professor

Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: Pirfenidone

Type: Active Comparator

Description: Pirfenidone will be started at a dose of 600 mg/day. The dose will be escalated by 600 mg/day every 3-7 days up to a targeted dose of 2400 mg/day. The subjects will be administered the maximum tolerated dose for a total period of 24 weeks from randomization.

Label: Nintedanib

Type: Active Comparator

Description: Subjects in this group will be administered nintedanib at a dose of 150 mg twice daily. The liver function tests will be monitored as above. The dose will be reduced to 100 mg twice daily, if there is intolerance to 300 mg/day dose.

Acronym PINCER
Patient Data No
Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Treatment

Masking: Single (Outcomes Assessor)

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