COVID 19
Conditions
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.
Interventions
DRUGNormal Saline intranasal and placebo inhaler
Normal Saline intranasal BID and Placebo 3 puff MDI inhaled BID
DRUGCiclesonide
Ciclesonide 600mcg BID inhaled with aero chamber
intranasal ciclesonide 200 mcg DIE
Sponsors
McGill University Health Centre/Research Institute of the McGill University Health Centre
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
| 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. |
| 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 |
| Proportion of Participants Hospitalized for SARS-CoV-2 | day 14 | Hospitalization for SARS-CoV-2 related illness |
| Mortality | day 29 | All cause mortality |
| 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 |
Countries
Canada
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 details
Overall, 215 participants were randomised, and the modified intention-to-treat population included 203 adults with respiratory symptoms or fever.
Participants by arm
| Arm | Count |
|---|---|
| Ciclesonide Inhaled and Nasal 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 | 105 |
| Placebo 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 | 98 |
| Total | 203 |
Baseline characteristics
| Characteristic | Total | Placebo | Ciclesonide Inhaled and Nasal |
|---|---|---|---|
| Age, Continuous | 35 years | 35 years | 35 years |
| Race/Ethnicity, Customized Ethnicity African canadian | 5 Participants | 2 Participants | 3 Participants |
| Race/Ethnicity, Customized Ethnicity Asian | 34 Participants | 16 Participants | 18 Participants |
| Race/Ethnicity, Customized Ethnicity Hispanic or Latino | 13 Participants | 7 Participants | 6 Participants |
| Race/Ethnicity, Customized Ethnicity Middle Eastern | 18 Participants | 12 Participants | 6 Participants |
| Race/Ethnicity, Customized Ethnicity Other | 5 Participants | 2 Participants | 3 Participants |
| Race/Ethnicity, Customized Ethnicity South Asian | 12 Participants | 6 Participants | 6 Participants |
| Race/Ethnicity, Customized Ethnicity White | 116 Participants | 53 Participants | 63 Participants |
| Region of Enrollment Canada British Columbia | 102 Participants | 51 Participants | 51 Participants |
| Region of Enrollment Canada Ontario | 32 Participants | 13 Participants | 19 Participants |
| Region of Enrollment Canada Quebec | 69 Participants | 34 Participants | 35 Participants |
| Sex: Female, Male Female | 109 Participants | 55 Participants | 54 Participants |
| Sex: Female, Male Male | 94 Participants | 43 Participants | 51 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 105 | 0 / 98 |
| other Total, other adverse events | 23 / 105 | 15 / 98 |
| serious Total, serious adverse events | 7 / 105 | 5 / 98 |
Outcome results
Primary
Proportion of Participants With no Symptoms of Cough, Fever or Dyspnea
Proportion of participants with no symptoms of cough, fever or dyspnea at day 7
Time frame: day 7
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ciclesonide Inhaled and Nasal | Proportion of Participants With no Symptoms of Cough, Fever or Dyspnea | 42 Participants |
| Placebo | Proportion of Participants With no Symptoms of Cough, Fever or Dyspnea | 34 Participants |
Secondary
Improvement in Cough at Day 7: Proportion of Patient With a Reduction of Cough Symptoms at 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
Time frame: day 7
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ciclesonide Inhaled and Nasal | Improvement in Cough at Day 7: Proportion of Patient With a Reduction of Cough Symptoms at Day 7 | 57 Participants |
| Placebo | Improvement in Cough at Day 7: Proportion of Patient With a Reduction of Cough Symptoms at Day 7 | 54 Participants |
Secondary
Improvement in Dyspnea: Resolution of Dyspnea at 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.
Time frame: day 7
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ciclesonide Inhaled and Nasal | Improvement in Dyspnea: Resolution of Dyspnea at Day 7 | 38 Participants |
| Placebo | Improvement in Dyspnea: Resolution of Dyspnea at Day 7 | 27 Participants |
Secondary
Mortality
All cause mortality
Time frame: day 29
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ciclesonide Inhaled and Nasal | Mortality | 0 Participants |
| Placebo | Mortality | 0 Participants |
Secondary
Overall Feeling: Proportion Who Are Reporting That They Are Very Much Improved or Much Improved at Day 14
Proportion who are reporting that they are very much improved or much improved
Time frame: Day 14
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ciclesonide Inhaled and Nasal | Overall Feeling: Proportion Who Are Reporting That They Are Very Much Improved or Much Improved at Day 14 | 95 Participants |
| Placebo | Overall Feeling: Proportion Who Are Reporting That They Are Very Much Improved or Much Improved at Day 14 | 91 Participants |
Secondary
Overall Feeling: Proportion Who Are Reporting That They Are Very Much Improved or Much Improved at Day 7
Proportion who are reporting that they are very much improved or much improved
Time frame: Day 7
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ciclesonide Inhaled and Nasal | Overall Feeling: Proportion Who Are Reporting That They Are Very Much Improved or Much Improved at Day 7 | 77 Participants |
| Placebo | Overall Feeling: Proportion Who Are Reporting That They Are Very Much Improved or Much Improved at Day 7 | 74 Participants |
Secondary
Proportion of Participants Hospitalized for SARS-CoV-2
Hospitalization for SARS-CoV-2 related illness
Time frame: day 14
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ciclesonide Inhaled and Nasal | Proportion of Participants Hospitalized for SARS-CoV-2 | 6 Participants |
| Placebo | Proportion of Participants Hospitalized for SARS-CoV-2 | 3 Participants |
Secondary
Proportion of Participants With no Symptoms of Cough, Fever or Dyspnea
Proportion of participants with no symptoms of cough, fever or dyspnea at Day 14
Time frame: Day 14
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ciclesonide Inhaled and Nasal | Proportion of Participants With no Symptoms of Cough, Fever or Dyspnea | 95 Participants |
| Placebo | Proportion of Participants With no Symptoms of Cough, Fever or Dyspnea | 91 Participants |