Clinical trial NCT04782700: P-Co-Li (Pulmonary Covid-19 Study)
Official title: P-CO-Li (Pulmonary Covid-19 Longterm Intervention Study)
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: NA
Conditions: Covid19
Lung Inflammation
Hypoxemic Respiratory Failure
Keywords: COVID19
Lead sponsor: Northwell Health
Sponsor class: OTHER
First posted: 2021-03-04
Enrollment: 0
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: The aim of this study is to determine whether the use of steroids versus watchful waiting improves pulmonary function tests in patients with history of COVID 19 infection who have residual hypoxemia and lung infiltrates. This is a non-inferiority trial which tests whether the outcomes after watchful waiting are not worst than after the use of steroids, with a margin of acceptable inferiority. The study team will limit inclusion to patients who have PCR- confirmed COVID19 at least in 10-weeks prior to enrollment, persistent opacities on chest imaging, and hypoxemia either at rest or during ambulation.

Detailed description: Rationale: The long-term pulmonary effects of COVID-19 infection have not been characterized. Many of the patients that have recovered from the initial infection still experience respiratory symptoms, require oxygen supplementation and/or have persistent opacities in chest imaging. The implications of these findings are not well described at this time, and it is unclear if these patients will eventually develop pulmonary fibrosis or fully recover. No standard therapy has been studied for this specific population and the use of steroids have only been tested in the acute setting. Outpatient providers are currently not sure whether to prescribe steroids or to carefully watch over time. This is a real-world question about which option is better and whether the risks of steroids outweigh the potential benefit when compared to watchful waiting. The investigator propose that watchful waiting is not inferior to the use of steroids in improving the pulmonary function tests of these patients at 12 weeks.

Methodology: The investigators will include patients with history of COVID-19 infection who have persistent opacities on chest imaging, and who are hypoxemic - either at rest or with ambulation, at least 10 weeks post-COVID19 PCR positivity. The study team will randomize patients in a 1:1 fashion to receive either watchful waiting vs. steroids. The study team will follow the patients over time with sequential pulmonary function tests and clinic visits at baseline, 12 weeks, 6 months and 12 months, 24 and 36 months. The first 12 weeks will include weekly brief phone calls to check on the patients and to ask them to rate their dyspnea on the modified Borg Dyspnea Scale. Thereafter, phone follow up will occur monthly.

Outcomes:

Outcomes will be measured at baseline, 12 weeks, 6-months, 12-months, 24-months, and 36-months. For the first 12 weeks weekly mBorg Dyspnea Scale will also be obtained.

The primary outcome will be worsening in pulmonary function tests (baseline to over 12 weeks), defined as absolute value of FVC worsened by \>10% OR absolute value of DLCO worsened by \>15%. As a real-world study, if patients are unable to receive PFTs before their physician decides to escalate therapy, a 2-point worsening (increase) in mBorg will be considered as patient having achieved the primary outcome.

The secondary outcomes will include collection of the following: (1) Hypoxemia (increased oxygen supplementation by 1L/min or \>3% decrease in pulse Ox at ambulation to HR number); (2) 6MWT (where possible); (3) SR-36 questionnaire; (4) PROMIS short forms; (5) mBorg Dyspnea Scale; (6) CT scan findings (where obtained as part of standard of care); and (7) PFT changes over time. All outcomes will be analyzed as binary variables (20% worsening Y/N or clinically meaningful worsening) from baseline, and as continuous variables to each time-point to follow-up.

The tertiary outcomes will include changes in COVID19 bundle labs ( inflammatory markers, D-dimer, metabolic panel, CBC, COVID IgG); radiographic improvement (where obtained as part of standard of care by the treating provider), HgA1c, pro-calcitonin, and documented infections. These values will be obtained from the medical record if already ordered by other providers, or will be ordered by the research team at the specified follow-up timepoints. Of note, radiology testing will not be ordered by the research team but will be at the discretion of the clinical providers who will be advised about clinic-set standards for frequency and timing of follow up.

Weekly phone call check-in will be made for the first 12-weeks asking mBorg, and monthly thereafter, and check-in clinic appointments will occur at 12 weeks and as needed.

Eligibility criteria: Inclusion Criteria:

1. Outpatients age\>18 with PCR positive COVID19 at least 4-weeks prior;
2. persistent opacities (GGO and/or reticular changes) on any chest imaging at least 4-weeks after positive COVID PCR;
3. HYPOXEMIA as defined by any of the below:

   1. Or patient already on supplemental oxygen
   2. Or room air saturation 94% or less

Exclusion Criteria:

1. age \<18
2. special populations (minors, pregnant women, decisional impairment which prevents them from making their own health decisions)
3. subjects with underlying ILD pre-COVID19 infection

Primary outcomes:
measure: Worsened pulmonary function test (PFT) (FVC or DLCO)
timeFrame: Baseline to 12-weeks
Secondary outcomes:
measure: Hypoxemia
timeFrame: Baseline to 12 weeks; and 6, 12, 24 and 36-months
measure: 6 Minute-Walk Test (6MWT)
timeFrame: Baseline to 12 weeks; and 6, 12, 24 and 36-months
measure: mBorg Dyspnea Scale
timeFrame: Baseline to 12 weeks; and 6, 12, 24 and 36-months
measure: PROMIS Short Forms Outcomes Survey
timeFrame: Baseline to 12 weeks; and 6, 12, 24 and 36-months
measure: Lower Extremity Functional Scale
timeFrame: Baseline to 12 weeks; and 6, 12, 24 and 36-months
measure: EQ-5D-5L outcomes survey
timeFrame: Baseline to 12 weeks; and 6, 12, 24 and 36-months
measure: Changes over time in CT chest sans
timeFrame: Baseline to 12 weeks; and 6, 12, 24 and 36-months
measure: Other pulmonary function test (PFT) changes over time
timeFrame: Baseline to 12 weeks; and 6, 12, 24 and 36-months
Other outcomes:
measure: Changes in COVID19 bundle labs
timeFrame: Baseline to 12 weeks; and 6, 12, 24 and 36-months
Locations:
city: Manhasset
country: United States
facility: Northwell Health
state: New York
Study officials:
affiliation: Northwell Health
name: Negin Hajizadeh, MD
role: PRINCIPAL_INVESTIGATOR
References: