CONTAIN: Inhaled Ciclesonide for Outpatients With COVID19

Sponsor
McGill University Health Centre/Research Institute of the McGill University Health Centre (Other)
Overall Status
Terminated
CT.gov ID
NCT04435795
Collaborator
(none)
215
3
2
9.7
71.7
7.4

Study Details

Study Description

Brief Summary

The CONTAIN (CiclesOnide cliNical TriAl covId-19 treatmeNt) is a randomized control study of ciclesonide vs placebo for mild covid-19 disease. The need for potential therapy for COVID-19 patients is urgent. Ciclesonide has shown encouraging in vitro results, is easy to be used and is readily available. It has a low rate of side effects and few interactions with other drugs. It is unusual to use an inhaled steroid drug for COVID-19 but there has been new data suggesting steroids may have an antiviral effect in addition to an anti-inflammatory effect. Investigators propose to use inhaled and nasal ciclesonide to stop viral replication in the nose and airways. Investigators hope this will accelerate recovery from COVID-19 illness in individuals who are not admitted to hospital at time of diagnosis of COVID-19.

Condition or Disease Intervention/Treatment Phase
  • Drug: Normal Saline intranasal and placebo inhaler
  • Drug: Ciclesonide
  • Drug: Ciclesonide nasal
Phase 2/Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
215 participants
Allocation:
Randomized
Intervention Model:
Factorial Assignment
Masking:
Triple (Participant, Care Provider, Investigator)
Primary Purpose:
Treatment
Official Title:
Ciclesonide Clinical Trial for COVID-19 Treatment
Actual Study Start Date :
Sep 15, 2020
Actual Primary Completion Date :
Jun 8, 2021
Actual Study Completion Date :
Jul 8, 2021

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Ciclesonide inhaled and nasal

Intranasal ciclesonide BID 50mcg BID to each nostril and inhaled ciclesonide 600mcg BID x 14 days

Drug: Ciclesonide
Ciclesonide 600mcg BID inhaled with aero chamber
Other Names:
  • Alvesco
  • Drug: Ciclesonide nasal
    intranasal ciclesonide 200 mcg DIE
    Other Names:
  • Omnaris
  • Placebo Comparator: Placebo

    Normal Saline intranasal BID and Placebo 3 puff MDI inhaled BID

    Drug: Normal Saline intranasal and placebo inhaler
    Normal Saline intranasal BID and Placebo 3 puff MDI inhaled BID

    Outcome Measures

    Primary Outcome Measures

    1. Proportion of Participants With no Symptoms of Cough, Fever or Dyspnea [day 7]

      Proportion of participants with no symptoms of cough, fever or dyspnea at day 7

    Secondary Outcome Measures

    1. Proportion of Participants With no Symptoms of Cough, Fever or Dyspnea [Day 14]

      Proportion of participants with no symptoms of cough, fever or dyspnea at Day 14

    2. Overall Feeling: Proportion Who Are Reporting That They Are "Very Much Improved" or "Much Improved" at Day 7 [Day 7]

      Proportion who are reporting that they are "very much improved" or "much improved"

    3. Overall Feeling: Proportion Who Are Reporting That They Are "Very Much Improved" or "Much Improved" at Day 14 [Day 14]

      Proportion who are reporting that they are "very much improved" or "much improved"

    4. Improvement in Dyspnea: Resolution of Dyspnea at Day 7 [day 7]

      Dyspnea was defined as reporting "shortness of breath" or "chest congestion" or "chest tightness". In those who reported dyspnea at baseline, resolution will be defined as having no symptoms in these three areas.

    5. Improvement in Cough at Day 7: Proportion of Patient With a Reduction of Cough Symptoms at Day 7 [day 7]

      Improvement of wet or dry cough. Analysis limited to patients who reported cough at baseline. Defined as a 2 point decrease, or a decrease to 0 on a visual analogue scale that ranged from 0 for no symptoms to 10 for severe symptoms

    6. Proportion of Participants Hospitalized for SARS-CoV-2 [day 14]

      Hospitalization for SARS-CoV-2 related illness

    7. Mortality [day 29]

      All cause mortality

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    Symptomatic adult patients positive by PCR for COVID-19 within 5 days of enrollment with fever, cough, or shortness of breath. Provision of Informed Consent

    At day 0, patients should be at home

    Exclusion Criteria:
    • Already on inhaled corticosteroid medication

    • Currently using systemic steroids (oral or intravenous or intramuscular such as Prednisone) or use of steroids 7 days prior to enrolment

    • Severely ill patients at enrollment (i.e., admitted to ICU at admission)

    • Unable to self-administer the inhaler

    • Known or suspected pregnancy and breastfeeding

    • Known allergy to study medication or its components (non-medicinal ingredients; including lactose allergy (type I))

    • Patients with untreated fungal, bacterial, or tubercular infections of the respiratory tract

    • Current hospitalization

    • Current use of oxygen at home or in the hospital

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of British Columbia Vancouver British Columbia Canada
    2 Sunnybrook Hospital Toronto Ontario Canada M4N 3M5
    3 McGill University Health Center Montreal Quebec Canada H3K 2M2

    Sponsors and Collaborators

    • McGill University Health Centre/Research Institute of the McGill University Health Centre

    Investigators

    None specified.

    Study Documents (Full-Text)

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Nicole Ezer, MD, FRCPC, MPH, Assistant Professor of Medicine, McGill University Health Centre/Research Institute of the McGill University Health Centre
    ClinicalTrials.gov Identifier:
    NCT04435795
    Other Study ID Numbers:
    • 2021-6696
    First Posted:
    Jun 17, 2020
    Last Update Posted:
    Jun 10, 2022
    Last Verified:
    May 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details Enrolment to the trial began on 15 September 2020 in Quebec, 9 February 2021 in Ontario, and 22 March 2021 in British Columbia. The last participants were recruited on 8 June 2021.
    Pre-assignment Detail Overall, 215 participants were randomised, and the modified intention-to-treat population included 203 adults with respiratory symptoms or fever.
    Arm/Group Title Ciclesonide Inhaled and Nasal Placebo
    Arm/Group Description Intranasal ciclesonide BID 50mcg BID to each nostril and inhaled ciclesonide 600mcg BID x 14 days Ciclesonide: Ciclesonide 600mcg BID inhaled with aero chamber Ciclesonide nasal: intranasal ciclesonide 200 mcg DIE Normal Saline intranasal BID and Placebo 3 puff MDI inhaled BID Normal Saline intranasal and placebo inhaler: Normal Saline intranasal BID and Placebo 3 puff MDI inhaled BID
    Period Title: Overall Study
    STARTED 108 107
    COMPLETED 105 98
    NOT COMPLETED 3 9

    Baseline Characteristics

    Arm/Group Title Ciclesonide Inhaled and Nasal Placebo Total
    Arm/Group Description Intranasal ciclesonide BID 50mcg BID to each nostril and inhaled ciclesonide 600mcg BID x 14 days Ciclesonide: Ciclesonide 600mcg BID inhaled with aero chamber Ciclesonide nasal: intranasal ciclesonide 200 mcg DIE Normal Saline intranasal BID and Placebo 3 puff MDI inhaled BID Normal Saline intranasal and placebo inhaler: Normal Saline intranasal BID and Placebo 3 puff MDI inhaled BID Total of all reporting groups
    Overall Participants 105 98 203
    Age (years) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [years]
    35
    35
    35
    Sex: Female, Male (Count of Participants)
    Female
    54
    51.4%
    55
    56.1%
    109
    53.7%
    Male
    51
    48.6%
    43
    43.9%
    94
    46.3%
    Race/Ethnicity, Customized (Count of Participants)
    African canadian
    3
    2.9%
    2
    2%
    5
    2.5%
    Asian
    18
    17.1%
    16
    16.3%
    34
    16.7%
    White
    63
    60%
    53
    54.1%
    116
    57.1%
    Hispanic or Latino
    6
    5.7%
    7
    7.1%
    13
    6.4%
    Middle Eastern
    6
    5.7%
    12
    12.2%
    18
    8.9%
    South Asian
    6
    5.7%
    6
    6.1%
    12
    5.9%
    Other
    3
    2.9%
    2
    2%
    5
    2.5%
    Region of Enrollment (Count of Participants)
    British Columbia
    51
    48.6%
    51
    52%
    102
    50.2%
    Ontario
    19
    18.1%
    13
    13.3%
    32
    15.8%
    Quebec
    35
    33.3%
    34
    34.7%
    69
    34%

    Outcome Measures

    1. Primary Outcome
    Title Proportion of Participants With no Symptoms of Cough, Fever or Dyspnea
    Description Proportion of participants with no symptoms of cough, fever or dyspnea at day 7
    Time Frame day 7

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Ciclesonide Inhaled and Nasal Placebo
    Arm/Group Description Intranasal ciclesonide BID 50mcg BID to each nostril and inhaled ciclesonide 600mcg BID x 14 days Ciclesonide: Ciclesonide 600mcg BID inhaled with aero chamber Ciclesonide nasal: intranasal ciclesonide 200 mcg DIE Normal Saline intranasal BID and Placebo 3 puff MDI inhaled BID Normal Saline intranasal and placebo inhaler: Normal Saline intranasal BID and Placebo 3 puff MDI inhaled BID
    Measure Participants 105 98
    Count of Participants [Participants]
    42
    40%
    34
    34.7%
    2. Secondary Outcome
    Title Proportion of Participants With no Symptoms of Cough, Fever or Dyspnea
    Description Proportion of participants with no symptoms of cough, fever or dyspnea at Day 14
    Time Frame Day 14

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Ciclesonide Inhaled and Nasal Placebo
    Arm/Group Description Intranasal ciclesonide BID 50mcg BID to each nostril and inhaled ciclesonide 600mcg BID x 14 days Ciclesonide: Ciclesonide 600mcg BID inhaled with aero chamber Ciclesonide nasal: intranasal ciclesonide 200 mcg DIE Normal Saline intranasal BID and Placebo 3 puff MDI inhaled BID Normal Saline intranasal and placebo inhaler: Normal Saline intranasal BID and Placebo 3 puff MDI inhaled BID
    Measure Participants 105 98
    Count of Participants [Participants]
    95
    90.5%
    91
    92.9%
    3. Secondary Outcome
    Title Overall Feeling: Proportion Who Are Reporting That They Are "Very Much Improved" or "Much Improved" at Day 7
    Description Proportion who are reporting that they are "very much improved" or "much improved"
    Time Frame Day 7

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Ciclesonide Inhaled and Nasal Placebo
    Arm/Group Description Intranasal ciclesonide BID 50mcg BID to each nostril and inhaled ciclesonide 600mcg BID x 14 days Ciclesonide: Ciclesonide 600mcg BID inhaled with aero chamber Ciclesonide nasal: intranasal ciclesonide 200 mcg DIE Normal Saline intranasal BID and Placebo 3 puff MDI inhaled BID Normal Saline intranasal and placebo inhaler: Normal Saline intranasal BID and Placebo 3 puff MDI inhaled BID
    Measure Participants 105 98
    Count of Participants [Participants]
    77
    73.3%
    74
    75.5%
    4. Secondary Outcome
    Title Overall Feeling: Proportion Who Are Reporting That They Are "Very Much Improved" or "Much Improved" at Day 14
    Description Proportion who are reporting that they are "very much improved" or "much improved"
    Time Frame Day 14

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Ciclesonide Inhaled and Nasal Placebo
    Arm/Group Description Intranasal ciclesonide BID 50mcg BID to each nostril and inhaled ciclesonide 600mcg BID x 14 days Ciclesonide: Ciclesonide 600mcg BID inhaled with aero chamber Ciclesonide nasal: intranasal ciclesonide 200 mcg DIE Normal Saline intranasal BID and Placebo 3 puff MDI inhaled BID Normal Saline intranasal and placebo inhaler: Normal Saline intranasal BID and Placebo 3 puff MDI inhaled BID
    Measure Participants 105 98
    Count of Participants [Participants]
    95
    90.5%
    91
    92.9%
    5. Secondary Outcome
    Title Improvement in Dyspnea: Resolution of Dyspnea at Day 7
    Description Dyspnea was defined as reporting "shortness of breath" or "chest congestion" or "chest tightness". In those who reported dyspnea at baseline, resolution will be defined as having no symptoms in these three areas.
    Time Frame day 7

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Ciclesonide Inhaled and Nasal Placebo
    Arm/Group Description Intranasal ciclesonide BID 50mcg BID to each nostril and inhaled ciclesonide 600mcg BID x 14 days Ciclesonide: Ciclesonide 600mcg BID inhaled with aero chamber Ciclesonide nasal: intranasal ciclesonide 200 mcg DIE Normal Saline intranasal BID and Placebo 3 puff MDI inhaled BID Normal Saline intranasal and placebo inhaler: Normal Saline intranasal BID and Placebo 3 puff MDI inhaled BID
    Measure Participants 53 49
    Count of Participants [Participants]
    38
    36.2%
    27
    27.6%
    6. Secondary Outcome
    Title Improvement in Cough at Day 7: Proportion of Patient With a Reduction of Cough Symptoms at Day 7
    Description Improvement of wet or dry cough. Analysis limited to patients who reported cough at baseline. Defined as a 2 point decrease, or a decrease to 0 on a visual analogue scale that ranged from 0 for no symptoms to 10 for severe symptoms
    Time Frame day 7

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Ciclesonide Inhaled and Nasal Placebo
    Arm/Group Description Intranasal ciclesonide BID 50mcg BID to each nostril and inhaled ciclesonide 600mcg BID x 14 days Ciclesonide: Ciclesonide 600mcg BID inhaled with aero chamber Ciclesonide nasal: intranasal ciclesonide 200 mcg DIE Normal Saline intranasal BID and Placebo 3 puff MDI inhaled BID Normal Saline intranasal and placebo inhaler: Normal Saline intranasal BID and Placebo 3 puff MDI inhaled BID
    Measure Participants 89 86
    Count of Participants [Participants]
    57
    54.3%
    54
    55.1%
    7. Secondary Outcome
    Title Proportion of Participants Hospitalized for SARS-CoV-2
    Description Hospitalization for SARS-CoV-2 related illness
    Time Frame day 14

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Ciclesonide Inhaled and Nasal Placebo
    Arm/Group Description Intranasal ciclesonide BID 50mcg BID to each nostril and inhaled ciclesonide 600mcg BID x 14 days Ciclesonide: Ciclesonide 600mcg BID inhaled with aero chamber Ciclesonide nasal: intranasal ciclesonide 200 mcg DIE Normal Saline intranasal BID and Placebo 3 puff MDI inhaled BID Normal Saline intranasal and placebo inhaler: Normal Saline intranasal BID and Placebo 3 puff MDI inhaled BID
    Measure Participants 105 98
    Count of Participants [Participants]
    6
    5.7%
    3
    3.1%
    8. Secondary Outcome
    Title Mortality
    Description All cause mortality
    Time Frame day 29

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Ciclesonide Inhaled and Nasal Placebo
    Arm/Group Description Intranasal ciclesonide BID 50mcg BID to each nostril and inhaled ciclesonide 600mcg BID x 14 days Ciclesonide: Ciclesonide 600mcg BID inhaled with aero chamber Ciclesonide nasal: intranasal ciclesonide 200 mcg DIE Normal Saline intranasal BID and Placebo 3 puff MDI inhaled BID Normal Saline intranasal and placebo inhaler: Normal Saline intranasal BID and Placebo 3 puff MDI inhaled BID
    Measure Participants 105 98
    Count of Participants [Participants]
    0
    0%
    0
    0%

    Adverse Events

    Time Frame 29 Days
    Adverse Event Reporting Description
    Arm/Group Title Ciclesonide Inhaled and Nasal Placebo
    Arm/Group Description Intranasal ciclesonide BID 50mcg BID to each nostril and inhaled ciclesonide 600mcg BID x 14 days Ciclesonide: Ciclesonide 600mcg BID inhaled with aero chamber Ciclesonide nasal: intranasal ciclesonide 200 mcg DIE Normal Saline intranasal BID and Placebo 3 puff MDI inhaled BID Normal Saline intranasal and placebo inhaler: Normal Saline intranasal BID and Placebo 3 puff MDI inhaled BID
    All Cause Mortality
    Ciclesonide Inhaled and Nasal Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/105 (0%) 0/98 (0%)
    Serious Adverse Events
    Ciclesonide Inhaled and Nasal Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 7/105 (6.7%) 5/98 (5.1%)
    Respiratory, thoracic and mediastinal disorders
    Hospithalization 6/105 (5.7%) 3/98 (3.1%)
    Visit to the emergency department 1/105 (1%) 3/98 (3.1%)
    Other (Not Including Serious) Adverse Events
    Ciclesonide Inhaled and Nasal Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 23/105 (21.9%) 15/98 (15.3%)
    General disorders
    Severe headache 13/105 (12.4%) 5/98 (5.1%)
    Voice change 2/105 (1.9%) 2/98 (2%)
    throat irritaiton 7/105 (6.7%) 5/98 (5.1%)
    Dry mouth 2/105 (1.9%) 3/98 (3.1%)
    Dry nose, irritated nose or nosebleed 4/105 (3.8%) 1/98 (1%)
    Dizziness 1/105 (1%) 0/98 (0%)
    Nausea 11/105 (10.5%) 2/98 (2%)
    Wheeze 0/105 (0%) 1/98 (1%)
    Other 6/105 (5.7%) 3/98 (3.1%)
    Respiratory, thoracic and mediastinal disorders
    Thrush 2/105 (1.9%) 0/98 (0%)

    Limitations/Caveats

    We were unable to recruit the intended sample size given a rapid decline in cases of covid-19 in Canada following increases in vaccination. In addition, we did not enrich the study population for older high risk people and cannot exclude a possible benefit in earlier symptom resolution and prevention of clinical deterioration in this group. As our trial was stopped prematurely, we might have been underpowered to show a small benefit of ciclesonide on early symptom resolution

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Dr Nicole EZER
    Organization Research Institute of the McGill University Health Center
    Phone 514-934-1934 ext 76192
    Email nicole.ezer@mcgill.ca
    Responsible Party:
    Nicole Ezer, MD, FRCPC, MPH, Assistant Professor of Medicine, McGill University Health Centre/Research Institute of the McGill University Health Centre
    ClinicalTrials.gov Identifier:
    NCT04435795
    Other Study ID Numbers:
    • 2021-6696
    First Posted:
    Jun 17, 2020
    Last Update Posted:
    Jun 10, 2022
    Last Verified:
    May 1, 2022