Protective Role of Inhaled Steroids for Covid-19 Infection (INHASCO)

• ClinicalTrials.gov Identifier: NCT04331054
• Recruitment Status: Terminated
• First Posted: April 2, 2020
• Last Update Posted: August 3, 2021
• Sponsor: Assistance Publique - Hôpitaux de Paris
• Information provided by (Responsible Party): Assistance Publique - Hôpitaux de Paris

Tracking Information

• First Submitted Date: March 29, 2020
• First Posted Date: April 2, 2020
• Last Update Posted Date: August 3, 2021
• Actual Study Start Date: April 13, 2020
• Actual Primary Completion Date: May 28, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 1, 2020)

Time (in days) to clinical improvement within 30 days after randomization [ Time Frame: within 30 days ]

Time (in days) to clinical improvement is defined as the time from randomization to an improvement of two points (from the status at randomization) on a seven-category ordinal scale or live discharge from the hospital, whichever came first within 30 days. The seven-category ordinal scale consisted of the following categories:

1. Not hospitalized with resumption of normal activities
2. Not hospitalized, but unable to resume normal activities
3. Hospitalized, not requiring supplemental oxygen
4. Hospitalized, requiring supplemental oxygen
5. Hospitalized, requiring nasal high-flow oxygen therapy, non-invasive mechanical ventilation, or both;
6. Hospitalized, requiring ECMO, invasive mechanical ventilation, or both
7. Death.

These parameters will be evaluated daily during hospitalization.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: April 1, 2020)

• Mortality rate at D30 [ Time Frame: At day30 ]
• Time (in days) from randomization to death [ Time Frame: up to 30 days after randomization ]
• Number of days alive outside ICU within 30 days [ Time Frame: At day30 ]
• Number of days alive free of invasive or non-invasive ventilation within 30 days [ Time Frame: At day30 ]
• Number of days alive with oxygen therapy within 30 days [ Time Frame: At day30 ]
• Maximal oxygen rate within 30 days [ Time Frame: At day30 ]
• Difference between PaO2/FiO2 ratio at randomization and at Day 7 (or at the time of stopping oxygen therapy or discharge if occurs before Day 7) [ Time Frame: at Day 7 ]
• Number of days alive outside hospital within 30 days [ Time Frame: at Day 30 ]
• Use of antibiotics for respiratory (proved or suspected) infection within 30 days [ Time Frame: at Day 30 ]
• Difference between CRP levels at randomization and at Day 7 (or at the time of discharge if occurs before Day 7) [ Time Frame: at Day 7 ]
• Safety outcomes included events that occurred during treatment, serious adverse events, and premature discontinuation of treatment. [ Time Frame: up to 30 days after randomization ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Protective Role of Inhaled Steroids for Covid-19 Infection
• Official Title: Protective Role of Inhaled Steroids for Covid-19 Infection

Brief Summary

We hypothesize that inhaled steroid therapy and long acting beta 2 adrenergic agonist, widely prescribed in asthma patients, may also have a local protective effect against coronavirus infection, even in patients without asthma.

The primary purpose is To compare time to clinical improvement in patients receiving standard of care associated to the combination budesonide/formoterol or standard of care only.

Time (in days) to clinical improvement is defined as the time from randomization to an improvement of two points (from the status at randomization) on a seven-category ordinal scale or live discharge from the hospital, whichever came first within 30 days.

Detailed Description

D1 inclusion / randomization visit:

Patients who meet the eligibility criteria and whose infection with Covid-19 has been confirmed within 48 hours will be included in the respiratory diseases department by the pneumologist investigator.

Patients will be randomized either to the control group or to the intervention group. For interventional patients, trial treatment (SYMBICORT RAPIHALER 200/6 µ) will begin within 12 hours.

Follow-up period (D2 to D29) and end of study visit (D30):

Throughout their hospital stay, patients will be followed in accordance with the practice of the service.

During hospitalization, investigators are free to decide for antibiotics, steroids, anti viral drugs, hydroxychloroquine and oxygen support management in accordance with local practice. None of the laboratory tests are made for the study. They are usually performed in patients hospitalized for acute respiratory infection.

Interventional patient will also be treated with SYMBICORT RAPIHALER 200/6 µg (2 puffs 2 times a day).

In the event that the patient is discharged from hospital before the end of his participation, he will be contacted by phone on D30 in order to obtain information concerning the period outside hospitalization

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Covid-19 Infection
• Hospitalization in Respiratory Disease Department

Intervention

• Drug: 2: Usual practice + SYMBICORT RAPIHALER
  2 puffs bid during 30 days by inhalation
• Other: 1: Usual practice
  Usual practice

Study Arms

• Active Comparator: 1: Usual practice
  arm will be follow during 30 days
  Intervention: Other: 1: Usual practice
• Experimental: 2: Usual practice + SYMBICORT RAPIHALER
  Usual practice + SYMBICORT RAPIHALER 200/6 µg ( 2 puffs bid during 30 days)
  Intervention: Drug: 2: Usual practice + SYMBICORT RAPIHALER

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: July 31, 2021): 146
• Original Estimated Enrollment (submitted: April 1, 2020): 436
• Actual Study Completion Date: May 28, 2021
• Actual Primary Completion Date: May 28, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion criera :

• Patient ≥ 18 years old and ≤ 75 years old
• Laboratory proved infection by COVID-19 by RT-PCR on a respiratory biological sample within 2 days
• Hospitalization is required according to current local recommendations
• Patient affiliated to a social security regime
• Patient able to give free, informed and written consent

Exclusion criteria :

• Oxygen flow rate >8l/min at inclusion
• Current treatment with any inhaled steroid (any other form of steroid administration does not exclude the patient)
• Intensive care unit is required for the patient (based on investigator judgement)
• Patient with cognitive impairment which do not guarantee proper use of the treatment by the patient himself
• Pregnant (positive β-HCG at inclusion) or breastfeeding women
• Participation in another interventional drug study involving human participants and concerning COVID-19 infection or being in the exclusion period of a previous study involving human participants
• Contraindications to the treatments (history of hypersensitivity)
• Patient admitted for isolation, for social reason or due to comorbidities without gravity sign
• Long-term patient treated with digitalis, disopyramide, procainamide or phenothiazine that could lengthen the QT space

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: France

Administrative Information

• NCT Number: NCT04331054
• Other Study ID Numbers: P 200394; 2020-001306-35 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

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

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Assistance Publique - Hôpitaux de Paris
• Original Responsible Party: Same as current
• Current Study Sponsor: Assistance Publique - Hôpitaux de Paris
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Camille TAILLE, MD, PhD; Assistance Publique - Hôpitaux de Paris

• PRS Account: Assistance Publique - Hôpitaux de Paris
• Verification Date: July 2021