Novel Coronavirus-induced Lung FibrosisPhase 4PINCERNCT04856111
Pirfenidone vs. Nintedanib for Fibrotic Lung Disease After Coronavirus Disease-19 Pneumonia
A Phase 4 study testing Pirfenidone and Nintedanib in people with Novel Coronavirus-induced Lung Fibrosis, run by Post Graduate Institute of Medical Education and Research, Chandigarh at 1 site in India.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Novel Coronavirus-induced Lung Fibrosis
- What is being tested?
- Pirfenidone and Nintedanib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 48 participants
- Where
- 1 siteIndia
- Study dates
- 17 Mar 2021to 30 Nov 2022
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age above 18 years
- 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
- Persistent respiratory symptoms
- 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
Who cannot join
- Pregnant or lactating women
- 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)
- Known patient with diffuse lung disease prior to the diagnosis of COVID
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Study of the Efficacy and Safety of Pirfenidone vs. Nintedanib in the Treatment of Fibrotic Lung Disease After Coronavirus Disease-19 Pneumonia
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.
Read the 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.
- Conditions
- Novel Coronavirus-induced Lung Fibrosis
- Being tested
- Pirfenidone, Nintedanib
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PirfenidoneDrug
Same as arm description
NintedanibDrug
Same as arm description
| Study group | Role | What they receive |
|---|---|---|
| Pirfenidone | Active comparator | 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. Receives: Drug: Pirfenidone |
| Nintedanib | Active comparator | 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. Receives: Drug: Nintedanib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in the forced vital capacity (FVC)
Forced vital capacity will be measured using spirometry. The predicted value will be calculated based on standard reference equations.
Measured: 24 weeks
Secondary outcomes (13)
Proportion of subjects with improvement or stabilization
This will be defined by improvement or a <10% relative decline in FVC from the baseline value
Measured: 24 weeks
Proportion of subjects with a good composite response
A good composite response will be defined as less than mMRC grade 2 breathlessness with ≥10% improvement in FVC with an oxygen saturation >92% during and after exertion.
Measured: 24 weeks
Change in dyspnea score on modified Medical Research Council scale
The change in dyspnea score assessed using the modified Medical Research Council from the day of randomization to 6 weeks.The scale has a minimum score of 0 and a maximum score of 4, higher values indicate worse outcomes
Measured: 24 weeks
Severity of dyspnea on the Functional Assessment of Chronic Illness Therapy - Dyspnea-10 item scale
Severity of dyspnea assessed using the Functional Assessment of Chronic Illness Therapy - Dyspnea-10 item scale. The scale has two item banks of 10 items each for dyspnea and functional limitations. EAch item has a minimum score of 0 and maximum score of 3. Higher scores represent worse outcomes.
Measured: 24 weeks
Change in resting oxygen saturation
The change in resting oxygen saturation (measured by pulse oximetry) from the day of randomization to 24 weeks
Measured: 24 weeks
Proportion of subjects with oxygen desaturation on exercise testing
Oxygen desaturation will be defined as a fall in oxygen saturation by 4% or more on exercise testing (by one-minute sit-to-stand test and six-minute walk test)
Measured: 24 weeks
Percentage change in the six-minute walk distance
Six-minute walk test will be performed by trained technicians using a standard protocol
Measured: 24 weeks
Proportion of participants who need rescue treatment
Rescue treatment would include the use of higher doses of glucocorticoids or other immunosuppressive agents
Measured: 24 weeks
Change in health-related quality of life using the Short Form-36 questionnaire
Health-related quality of life assessed using Short Form-36 questionnaire. The questionnaire consists of 36 items covering 8 domains. Each domain score has a minimum value of 0 and maximum value of 100, with higher scores representing better outcomes
Measured: 24 weeks
Change in respiratory health status using the King's Brief ILD questionnaire
Respiratory health status assessed using the King's Brief ILD questionnaire. The questionnaire has 15 items. The total score varies from 0 to 100, with higher scores representing better outcomes.
Measured: 24 weeks
Changes in HRCT scores using the modified Salisbury system
Changes in HRCT scores for different features (reticulation, honeycombing, ground-glass opacities, mosaic attenuation/air trapping) will be calculated. The score for each feature range from 0 to 5 with higher scores representing worse outcomes
Measured: 24 weeks
Proportion of subjects who develop adverse effects due to either study drug
The adverse effects of treatment (rash, hepatotoxicity, nausea, vomiting, diarrhea, headache, abdominal pain)
Measured: 24 weeks
Predictors of response to antifibrotic agents, pirfenidone and nintedanib
These may include age, gender, the study group, baseline CT abnormalities, baseline FVC
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Apr 2021
- Study start17 Mar 2021
- Primary completion30 Nov 2022 (estimated)
- Study completion30 Nov 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Novel Coronavirus-induced Lung FibrosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 48 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Post Graduate Institute of Medical Education and Research, Chandigarh
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Sahajal Dhooria, Post Graduate Institute of Medical Education and Research, Chandigarh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04856111
- Sponsor's protocol ID
- INT/IEC/2021/SPL-462
- Acronym
- PINCER
- Status last verified
- Sep 2022
- First submitted
- 19 Apr 2021
- Last updated
- 3 Oct 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Study of the Efficacy and Safety of Pirfenidone vs. Nintedanib in the Treatment of Fibrotic Lung Disease After Coronavirus Disease-19 Pneumonia
- ClinicalTrials.gov ID
- NCT04856111
- Acronym / sponsor ID
- PINCER / INT/IEC/2021/SPL-462
- Conditions
- Novel Coronavirus-induced Lung Fibrosis
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 48 participants (estimated)
- Lead sponsor
- Post Graduate Institute of Medical Education and Research, ChandigarhUniversity, hospital or other
- Study start
- 17 Mar 2021 (actual)
- Primary completion
- 30 Nov 2022 (estimated)
- Study completion
- 30 Nov 2022 (estimated)
- First posted
- 22 Apr 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pirfenidone | Active comparator | Drug: PirfenidonePirfenidone 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. |
| Nintedanib | Active comparator | Drug: NintedanibSubjects 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Age above 18 years
- 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
- Persistent respiratory symptoms
- 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
Key exclusion criteria (3 listed)
- Pregnant or lactating women
- 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)
- Known patient with diffuse lung disease prior to the diagnosis of COVID
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PirfenidoneSame as arm description | Drug | Pirfenidone |
| NintedanibSame as arm description | Drug | Nintedanib |
Primary outcome
Change in the forced vital capacity (FVC)
Time frame: 24 weeks
Forced vital capacity will be measured using spirometry. The predicted value will be calculated based on standard reference equations.
13 secondary outcomes
Proportion of subjects with improvement or stabilization
Time frame: 24 weeks
Proportion of subjects with a good composite response
Time frame: 24 weeks
Change in dyspnea score on modified Medical Research Council scale
Time frame: 24 weeks
Severity of dyspnea on the Functional Assessment of Chronic Illness Therapy - Dyspnea-10 item scale
Time frame: 24 weeks
Change in resting oxygen saturation
Time frame: 24 weeks
Proportion of subjects with oxygen desaturation on exercise testing
Time frame: 24 weeks
Percentage change in the six-minute walk distance
Time frame: 24 weeks
Proportion of participants who need rescue treatment
Time frame: 24 weeks
Change in health-related quality of life using the Short Form-36 questionnaire
Time frame: 24 weeks
Change in respiratory health status using the King's Brief ILD questionnaire
Time frame: 24 weeks
Changes in HRCT scores using the modified Salisbury system
Time frame: 24 weeks
Proportion of subjects who develop adverse effects due to either study drug
Time frame: 24 weeks
Predictors of response to antifibrotic agents, pirfenidone and nintedanib
Time frame: 24 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Oct 2022.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Pirfenidone and Nintedanib in people with Novel Coronavirus-induced Lung Fibrosis, run by Post Graduate Institute of Medical Education and Research, Chandigarh at 1 site in India.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 3 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in India. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in the forced vital capacity (FVC) (time frame: 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Oct 2022.