Comparison of Two Corticosteroid Regimens for Post COVID-19 Diffuse Lung Disease (COLDSTER)

• ClinicalTrials.gov Identifier: NCT04657484
• Recruitment Status: Recruiting
• First Posted: December 8, 2020
• Last Update Posted: December 22, 2020
• Sponsor: Postgraduate Institute of Medical Education and Research
• Information provided by (Responsible Party): Sahajal Dhooria, Postgraduate Institute of Medical Education and Research

Study Description

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, we 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.

Condition or disease	Intervention/treatment	Phase
Post COVID-19 Diffuse Lung Disease	Drug: Medium dose prednisolone; Drug: Low dose prednisolone	Not Applicable

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.

We 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

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 100 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: December 8, 2020
• Estimated Primary Completion Date: December 7, 2021
• Estimated Study Completion Date: December 7, 2021

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Medium dose prednisolone; 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	Drug: Medium dose prednisolone; Same as arm description
Active Comparator: Low dose prednisolone; A dose of 10 mg/day of prednisolone will be administered for 6 weeks	Drug: Low dose prednisolone; Same as arm description

Outcome Measures

Primary Outcome Measures :

1. 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

Secondary Outcome Measures :

1. Proportion of subjects with a complete or good response 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. Good response is defined as ≥50% but less than 90% reduction in the lung parenchymal abnormalities on a high-resolution CT scan.
2. Proportion of subjects with a good composite response [ Time Frame: 6 weeks ]
   Complete or good radiologic resolution along with no oxygen desturation on exercise testing
3. Forced vital capacity as a percentage of the predicted [ Time Frame: 6 weeks ]
   Forced vital capacity will be measured using spirometry. The predicted value will be calculated based on standard reference equations.
4. Change in resting oxygen saturation [ Time Frame: 6 weeks ]
   The change in resting oxygen saturation (measured by pulse oximetry) from the day of randomization to 6 weeks
5. Proportion of subjects with oxygen desaturation on exercise testing [ Time Frame: 6 weeks ]
   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)
6. Change in dyspnea score [ Time Frame: 6 weeks ]
   The change in dyspnea score assessed using the modified Medical Research Council (mMRC) scale from the day of randomization to 6 weeks
7. Severity of dyspnea [ Time Frame: 6 weeks ]
   Severity of dyspnea assessed using the FACIT-Dyspnea scale
8. Respiratory health status [ Time Frame: 6 weeks ]
   Respiratory health status assessed using the King's Brief ILD questionnaire
9. Health-related quality of life [ Time Frame: 6 weeks ]
   Health-related quality of life assessed using Short Form-36 questionnaire
10. Adverse effects of prednisolone [ Time Frame: 6 weeks ]
    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)

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Contacts

Contact: Sahajal Dhooria, MD, DM; +919530661388; sahajal@gmail.com

Locations

India

Postgraduate Institute of Medical Education and Research; Recruiting

Chandigarh, India, 160012

Contact: Ritesh Agarwal, MD, DM +911722756825 agarwal.ritesh@outlook.in

Sponsors and Collaborators

Postgraduate Institute of Medical Education and Research

More Information

• Responsible Party: Sahajal Dhooria, Assistant Professor, Postgraduate Institute of Medical Education and Research
• ClinicalTrials.gov Identifier: NCT04657484
• Other Study ID Numbers: INT/IEC/2020/SPL-1528
• First Posted: December 8, 2020
• Last Update Posted: December 22, 2020
• Last Verified: December 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Sahajal Dhooria, Postgraduate Institute of Medical Education and Research:

diffuse parenchymal lung disease; interstitial lung disease; organizing pneumonia; coronavirus disease-2019; SARS-Co-V-2

Additional relevant MeSH terms:

Lung Diseases; Respiratory Tract Diseases; Prednisolone; Methylprednisolone Acetate; Methylprednisolone; Methylprednisolone Hemisuccinate; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Antineoplastic Agents, Hormonal; Antineoplastic Agents; Antiemetics; Autonomic Agents; Peripheral Nervous System Agents; Gastrointestinal Agents; Neuroprotective Agents; Protective Agents