Post COVID-19 Diffuse Lung DiseaseCOLDSTERNCT04657484
Comparison of Two Corticosteroid Regimens for Post COVID-19 Diffuse Lung Disease
A study testing Medium dose prednisolone and Low dose prednisolone in people with Post COVID-19 Diffuse Lung Disease, run by Post Graduate Institute of Medical Education and Research, Chandigarh at 1 site in India.
Trial summary
A proportion of patients with COVID-19 pneumonia have a prolonged course of illness. Some of these patients continue to have considerable respiratory symptoms or persistent hypoxemia. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Post COVID-19 Diffuse Lung Disease
- What is being tested?
- Medium dose prednisolone and Low dose prednisolone
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 130 participants
- Where
- 1 siteIndia
- Study dates
- 1 Dec 2020to 1 Sep 2021
- Phase
- Interventional
- 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
- 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 the detection of COVID-19 antigen
- Having significant respiratory symptoms (cough and breathlessness) or persistent hypoxemia or oxygen desaturation on exercise and CT chest showing residual changes of post-COVID parenchymal involvement of any extent OR having CT chest showing residual changes of post-COVID parenchymal involvement >20% of the lung parenchyma on visual inspection of the scans between 3-8 weeks of the onset of symptoms of COVID-19
- Willing to participate in the study
Who cannot join
- Receiving ventilatory or respiratory support (invasive or non-invasive mechanical ventilation or high flow nasal cannula) or supplemental oxygen with FiO2>0.35
- Requiring intensive care due to acute COVID-19 pneumonia or its complications
- Having a known lung parenchymal lung disease before the onset of COVID-19
- Pregnant or lactating women
- Having absolute contraindication for prednisolone in a dose of 40 mg/day (this includes untreated glaucoma, uncontrolled diabetes mellitus, signs of an uncontrolled or untreated infection or sepsis, pulmonary mycosis, untreated severe psychiatric disorders)
- Unwilling to provide informed consent
Trial locations and contacts
1 site in 1 country.
India1 site
Postgraduate Institute of Medical Education and Research
Chandigarh, 160012
About this study
Official title: Comparison of the Efficacy and Safety of Two Corticosteroid Regimens in the Treatment of Diffuse Lung Disease After Coronavirus Disease 2019 (COVID-19) Pneumonia
A proportion of patients with COVID-19 pneumonia have a prolonged course of illness. Some of these patients continue to have considerable respiratory symptoms or persistent hypoxemia. The CT abnormalities in these patients are often a combination of ground-glass opacities and patchy multifocal consolidation consistent with a pattern of OP. In several patients, these radiologic abnormalities persist. As with other forms of OP, patients with post-COVID OP or post COVID diffuse lung disease (PC-DLD) may benefit from treatment with oral glucocorticoids. The ideal dose of glucocorticoids for treating PC-DLD is unknown.
In this study, the investigatros aim to compare the efficacy and safety of a medium dose and a low dose of prednisolone (as the initial dose) for the treatment of post-COVID. diffuse lung disease.
Read the detailed description
A proportion of patients with COVID-19 pneumonia (with or without ARDS) have a prolonged course of illness. Some of these patients continue to have considerable respiratory symptoms or persistent hypoxemia. The CT abnormalities in these patients are often a combination of ground-glass opacities and patchy multifocal consolidation consistent with a pattern of OP. In several patients, these radiologic abnormalities persist even after the symptoms of active COVID-19 have subsided and swabs from the upper respiratory tract for SARS-CoV-2 have turned negative. Such patients may be classified as having a secondary form of OP, namely post-infectious OP. Some of the patients also start developing signs of fibrosis.
As with other forms of OP, patients with post-COVID OP or post COVID diffuse lung disease (PC-DLD) may benefit from treatment with oral glucocorticoids.
Glucocorticoids may be a double-edged sword in this clinical situation. Steroids reduce inflammation associated with OP with a resultant resolution of symptoms, improvement in gas exchange (resulting in the resolution of hypoxemia), and potentially preventing the progression of early parenchymal abnormalities to irreversible fibrosis. However, they are associated with adverse effects such as hyperglycemia, delayed viral clearance, and increased susceptibility to infections. The ideal dose of glucocorticoids for treating PC-DLD is unknown. As PC-DLD is likely to get recognised early (much earlier than the average duration between onset of symptoms and diagnosis in other forms of OP, i.e., about 3-6 months), there is a possibility a lower intensity of glucocorticoids may be sufficient for treatment than the usual regimens, with the advantage of lesser adverse effects. A previous retrospective study that compared two regimens (higher dose intensity [DI] of glucocorticoids alone vs. glucocorticoids at a lower dose intensity along with clarithromycin), however, found that a complete radiologic response was higher in the prednisone alone (higher DI) group (81% vs. 63%) than in the combination group (with a lower DI of prednisone). Statistical significance was however not achieved (p=0.38), mainly due to the small sample size.
The investiagtors hypothesize that in PC-DLD a higher intensity (i.e., starting with a medium dose of prednisolone) will be more effective than a lower dose intensity (i.e., starting with a low dose of prednisolone) of glucocorticoids in effecting a radiologic response at six weeks.
- Conditions
- Post COVID-19 Diffuse Lung Disease
- Being tested
- Medium dose prednisolone, Low dose prednisolone
- Keywords
- diffuse parenchymal lung disease, interstitial lung disease, organizing pneumonia, coronavirus disease-2019, SARS-Co-V-2
- Medical subject headings
- Lung Diseases, Interstitial, Organizing Pneumonia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Medium dose prednisoloneDrug
Same as arm description
Low dose prednisoloneDrug
Same as arm description
| Study group | Role | What they receive |
|---|---|---|
| Medium dose prednisolone | Active comparator | An initial dose of 40 mg/day will be administered for 1 week, followed by 30 mg/day for 1 week, 20 mg/day for 2 weeks, 10 mg/day for 2 weeks Receives: Drug: Medium dose prednisolone |
| Low dose prednisolone | Active comparator | A dose of 10 mg/day of prednisolone will be administered for 6 weeks Receives: Drug: Low dose prednisolone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of subjects with a complete radiologic response
Complete response is defined as complete disappearance or ≥90% reduction in the lung parenchymal abnormalities on a high-resolution CT scan
Measured: 6 weeks
Secondary outcomes (10)
Proportion of subjects with a complete or good response radiologic response
Complete response is defined as complete disappearance or ≥90% reduction in the lung parenchymal abnormalities on a high-resolution CT scan. Good response is defined as ≥50% but less than 90% reduction in the lung parenchymal abnormalities on a high-resolution CT scan.
Measured: 6 weeks
Proportion of subjects with a good composite response
Complete or good radiologic resolution along with no oxygen desturation on exercise testing and a normal spirometry
Measured: 6 weeks
Forced vital capacity as a percentage of the predicted
Forced vital capacity will be measured using spirometry. The predicted value will be calculated based on standard reference equations.
Measured: 6 weeks
Change in resting oxygen saturation
The change in resting oxygen saturation (measured by pulse oximetry) from the day of randomization to 6 weeks
Measured: 6 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: 6 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: 6 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: 6 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: 6 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: 6 weeks
Proportion of subjects who develop adverse effects of prednisolone
The adverse effects of treatment (acne, weight gain, hyperglycemia, hypertension, abdominal pain, dyspepsia, Cushingoid facies, skin thinning and bruising, mood changes, muscular weakness and any other adverse effects related to prednisolone)
Measured: 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Dec 2020
- Study start1 Dec 2020
- Primary completion1 Sep 2021
- Study completion1 Sep 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Post COVID-19 Diffuse Lung DiseaseStudies 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 130 participants (actual)
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
- NCT04657484
- Sponsor's protocol ID
- INT/IEC/2020/SPL-1528
- Acronym
- COLDSTER
- Status last verified
- Apr 2022
- First submitted
- 5 Dec 2020
- Last updated
- 26 Apr 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Dhooria S, Chaudhary S, Sehgal IS, Agarwal R, Arora S, Garg M, Prabhakar N, Puri GD, Bhalla A, Suri V, Yaddanapudi LN, Muthu V, Prasad KT, Aggarwal AN. High-dose versus low-dose prednisolone in symptomatic patients with post-COVID-19 diffuse parenchymal lung abnormalities: an open-label, randomised trial (the COLDSTER trial). Eur Respir J. 2022 Feb 17;59(2):2102930. doi: 10.1183/13993003.02930-2021. Print 2022 Feb.
PubMed 34887325
Study at a glance
From the registry record, last updated by the sponsor on 26 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparison of the Efficacy and Safety of Two Corticosteroid Regimens in the Treatment of Diffuse Lung Disease After Coronavirus Disease 2019 (COVID-19) Pneumonia
- ClinicalTrials.gov ID
- NCT04657484
- Acronym / sponsor ID
- COLDSTER / INT/IEC/2020/SPL-1528
- Conditions
- Post COVID-19 Diffuse Lung Disease
- Keywords
- diffuse parenchymal lung disease, interstitial lung disease, organizing pneumonia, coronavirus disease-2019, SARS-Co-V-2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 130 participants (actual)
- Lead sponsor
- Post Graduate Institute of Medical Education and Research, ChandigarhUniversity, hospital or other
- Study start
- 1 Dec 2020 (actual)
- Primary completion
- 1 Sep 2021 (actual)
- Study completion
- 1 Sep 2021 (actual)
- First posted
- 8 Dec 2020 (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.
A proportion of patients with COVID-19 pneumonia have a prolonged course of illness. Some of these patients continue to have considerable respiratory symptoms or persistent hypoxemia. The CT abnormalities in these patients are often a combination of ground-glass opacities and patchy multifocal consolidation consistent with a pattern of OP. In several patients, these radiologic abnormalities persist. As with other forms of OP, patients with post-COVID OP or post COVID diffuse lung disease (PC-DLD) may benefit from treatment with oral glucocorticoids. The ideal dose of glucocorticoids for treating PC-DLD is unknown.
In this study, the investigatros aim to compare the efficacy and safety of a medium dose and a low dose of prednisolone (as the initial dose) for the treatment of post-COVID. diffuse lung disease.
Detailed description
A proportion of patients with COVID-19 pneumonia (with or without ARDS) have a prolonged course of illness. Some of these patients continue to have considerable respiratory symptoms or persistent hypoxemia. The CT abnormalities in these patients are often a combination of ground-glass opacities and patchy multifocal consolidation consistent with a pattern of OP. In several patients, these radiologic abnormalities persist even after the symptoms of active COVID-19 have subsided and swabs from the upper respiratory tract for SARS-CoV-2 have turned negative. Such patients may be classified as having a secondary form of OP, namely post-infectious OP. Some of the patients also start developing signs of fibrosis.
As with other forms of OP, patients with post-COVID OP or post COVID diffuse lung disease (PC-DLD) may benefit from treatment with oral glucocorticoids.
Glucocorticoids may be a double-edged sword in this clinical situation. Steroids reduce inflammation associated with OP with a resultant resolution of symptoms, improvement in gas exchange (resulting in the resolution of hypoxemia), and potentially preventing the progression of early parenchymal abnormalities to irreversible fibrosis. However, they are associated with adverse effects such as hyperglycemia, delayed viral clearance, and increased susceptibility to infections. The ideal dose of glucocorticoids for treating PC-DLD is unknown. As PC-DLD is likely to get recognised early (much earlier than the average duration between onset of symptoms and diagnosis in other forms of OP, i.e., about 3-6 months), there is a possibility a lower intensity of glucocorticoids may be sufficient for treatment than the usual regimens, with the advantage of lesser adverse effects. A previous retrospective study that compared two regimens (higher dose intensity [DI] of glucocorticoids alone vs. glucocorticoids at a lower dose intensity along with clarithromycin), however, found that a complete radiologic response was higher in the prednisone alone (higher DI) group (81% vs. 63%) than in the combination group (with a lower DI of prednisone). Statistical significance was however not achieved (p=0.38), mainly due to the small sample size.
The investiagtors hypothesize that in PC-DLD a higher intensity (i.e., starting with a medium dose of prednisolone) will be more effective than a lower dose intensity (i.e., starting with a low dose of prednisolone) of glucocorticoids in effecting a radiologic response at six weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Medium dose prednisolone | Active comparator | Drug: Medium dose prednisoloneAn initial dose of 40 mg/day will be administered for 1 week, followed by 30 mg/day for 1 week, 20 mg/day for 2 weeks, 10 mg/day for 2 weeks |
| Low dose prednisolone | Active comparator | Drug: Low dose prednisoloneA dose of 10 mg/day of prednisolone will be administered for 6 weeks |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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 the detection of COVID-19 antigen
- Having significant respiratory symptoms (cough and breathlessness) or persistent hypoxemia or oxygen desaturation on exercise and CT chest showing residual changes of post-COVID parenchymal involvement of any extent OR having CT chest showing residual changes of post-COVID parenchymal involvement >20% of the lung parenchyma on visual inspection of the scans between 3-8 weeks of the onset of symptoms of COVID-19
- Willing to participate in the study
Key exclusion criteria (6 listed)
- Receiving ventilatory or respiratory support (invasive or non-invasive mechanical ventilation or high flow nasal cannula) or supplemental oxygen with FiO2>0.35
- Requiring intensive care due to acute COVID-19 pneumonia or its complications
- Having a known lung parenchymal lung disease before the onset of COVID-19
- Pregnant or lactating women
- Having absolute contraindication for prednisolone in a dose of 40 mg/day (this includes untreated glaucoma, uncontrolled diabetes mellitus, signs of an uncontrolled or untreated infection or sepsis, pulmonary mycosis, untreated severe psychiatric disorders)
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 |
|---|---|---|
| Medium dose prednisoloneSame as arm description | Drug | Medium dose prednisolone |
| Low dose prednisoloneSame as arm description | Drug | Low dose prednisolone |
Primary outcome
Proportion of subjects with a complete radiologic response
Time frame: 6 weeks
Complete response is defined as complete disappearance or ≥90% reduction in the lung parenchymal abnormalities on a high-resolution CT scan
10 secondary outcomes
Proportion of subjects with a complete or good response radiologic response
Time frame: 6 weeks
Proportion of subjects with a good composite response
Time frame: 6 weeks
Forced vital capacity as a percentage of the predicted
Time frame: 6 weeks
Change in resting oxygen saturation
Time frame: 6 weeks
Proportion of subjects with oxygen desaturation on exercise testing
Time frame: 6 weeks
Change in dyspnea score on modified Medical Research Council scale
Time frame: 6 weeks
Severity of dyspnea on the Functional Assessment of Chronic Illness Therapy - Dyspnea-10 item scale
Time frame: 6 weeks
Change in respiratory health status using the King's Brief ILD questionnaire
Time frame: 6 weeks
Change in health-related quality of life using the Short Form-36 questionnaire
Time frame: 6 weeks
Proportion of subjects who develop adverse effects of prednisolone
Time frame: 6 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Apr 2022.
- Derived from this study: PubMed 34887325Dhooria S, Chaudhary S, Sehgal IS, Agarwal R, Arora S, Garg M, Prabhakar N, Puri GD, Bhalla A, Suri V, Yaddanapudi LN, Muthu V, Prasad KT, Aggarwal AN. High-dose versus low-dose prednisolone in symptomatic patients with post-COVID-19 diffuse parenchymal lung abnormalities: an open-label, randomised trial (the COLDSTER trial). Eur Respir J. 2022 Feb 17;59(2):2102930. doi: 10.1183/13993003.02930-2021. Print 2022 Feb.
- Individual participant dataSharing planned: Undecided
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 study testing Medium dose prednisolone and Low dose prednisolone in people with Post COVID-19 Diffuse Lung Disease, 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 3 inclusion and 6 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: finished, as of the sponsor's last update on 26 Apr 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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Proportion of subjects with a complete radiologic response (time frame: 6 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04657484, which also lists 1 linked publication.
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 26 Apr 2022.