Clinical trial NCT04657484: Comparison of Two Corticosteroid Regimens for Post COVID-19 Diffuse Lung Disease
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Post COVID-19 Diffuse Lung Disease
Keywords: diffuse parenchymal lung disease
interstitial lung disease
organizing pneumonia
coronavirus disease-2019
SARS-Co-V-2
Lead sponsor: PGIMER
Sponsor class: UNKNOWN
First posted: 2020-12-08
Enrollment: 130
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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. 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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Proportion of subjects with a complete radiologic response
timeFrame: 6 weeks
Secondary outcomes:
measure: Proportion of subjects with a complete or good response radiologic response
timeFrame: 6 weeks
measure: Proportion of subjects with a good composite response
timeFrame: 6 weeks
measure: Forced vital capacity as a percentage of the predicted
timeFrame: 6 weeks
measure: Change in resting oxygen saturation
timeFrame: 6 weeks
measure: Proportion of subjects with oxygen desaturation on exercise testing
timeFrame: 6 weeks
measure: Change in dyspnea score on modified Medical Research Council scale
timeFrame: 6 weeks
measure: Severity of dyspnea on the Functional Assessment of Chronic Illness Therapy - Dyspnea-10 item scale
timeFrame: 6 weeks
measure: Change in respiratory health status using the King's Brief ILD questionnaire
timeFrame: 6 weeks
measure: Change in health-related quality of life using the Short Form-36 questionnaire
timeFrame: 6 weeks
measure: Proportion of subjects who develop adverse effects of prednisolone
timeFrame: 6 weeks
Other outcomes:
Locations:
city: Chandigarh
country: India
facility: Postgraduate Institute of Medical Education and Research
Study officials:
References:
citation: 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.