Back to resultsA Study to Assess Efficacy and Safety of RESP301 Plus Standard of Care (SOC) Compared to SOC Alone in Hospitalized Participants With COVID-19
Primary Purpose
COVID-19
Status
Completed
Phase
Phase 2
Locations
United Kingdom
Study Type
Interventional
Intervention
RESP301, a Nitric Oxide generating solution
Standard of Care
Sponsored by
About this trial
This is an interventional treatment trial for COVID-19
Eligibility Criteria
Inclusion Criteria:
- Participant has laboratory-confirmed SARS-CoV-2 infection as determined by reverse transcriptase polymerase chain reaction (RT-PCR) or other approved clinical testing prior to randomization.
- Participant is hospitalized in relation to COVID-19, requiring supplemental oxygen to maintain SpO2 at a safe level (WHO level 3 & 4).
- Participant is capable of giving signed informed consent
- Participant is male or female. All females of childbearing potential, including pregnant females, must consent to urine pregnancy testing at screening to be eligible for the study.
Exclusion Criteria:
- Rapidly deteriorating or likely to require escalation to high flow oxygen, invasive or non-invasive ventilatory support within 24 hours according to Investigator's opinion.
- Unable to safely receive a nebulized treatment for approximately 8 minutes according to Investigator's opinion.
- Unable to receive or considered ineligible for invasive or non-invasive ventilatory support.
- History of methemoglobinemia.
- Presence of uncontrolled asthma, history of severe bronchospasm.
- Presence of severe chronic respiratory disease and tracheostomy.
- Suspected or confirmed untreated, active tuberculosis.
- Severely immune-compromised participants in Investigator's opinion.
- Recent active coronary artery disease or decompensated heart failure.
Sites / Locations
- Imperial College Healthcare NHS Trust, St. Mary's Hospital
- Royal Preston Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Investigational arm
Control arm
Arm Description
Participants will receive inhaled RESP301 administered using a nebulizer three times a day for up to 10 days in addition to the standard of care.
Participants will receive institutional SOC for the treatment of COVID-19
Outcomes
Primary Outcome Measures
Number of Participants Who Progress by at Least One Level Higher on the Modified WHO Ordinal Scale
A modified WHO ordinal scale was used for consistency with the recent study in adults hospitalized with severe COVID-19, to record the participant's status at the time of assessment. The modified WHO ordinal scale included the following levels :
1= Not hospitalized, no limitations on activities; 2= Not hospitalized, limitation on activities; 3= Hospitalized, not requiring supplemental oxygen; 4= Hospitalized, requiring supplemental oxygen; 5= Hospitalized, on non-invasive ventilation or high-flow oxygen devices; 6= Hospitalized, on invasive mechanical ventilation or extra corporeal membrane oxygenation (ECMO); 7= Death. Higher scores mean worse outcome. The number of participants that had an increase in at least one level higher score on the modified WHO ordinal scale was assessed.
Secondary Outcome Measures
Change in Room Air Oxygen Saturation (SpO2) From Baseline Over Time
Pulse oximetry measurements were performed to evaluate SpO2. The effect of RESP301 as measured by room air SpO2 was assessed.
Change in National Early Warning Score (NEWS) 2 Symptom Score From Baseline Over Time
The NEWS is based on a simple aggregate scoring system in which a score is allocated to physiological measurements, already recorded in routine practice, when patients present to, or are being monitored in hospital. Six simple physiological parameters form the basis of the scoring system: 1. Respiration rate; 2. Oxygen saturation; 3. Systolic blood pressure; 4. Pulse rate; 5. Level of consciousness or new confusion; 6. Temperature.
Each score is 0-3 and individual scores are added together for an overall score. An additional two points are added if the patient is receiving oxygen therapy. The total possible score ranges from 0 to 20. The higher the score the greater the clinical risk. Higher scores indicate the need for escalation, medical review and possible clinical intervention, and more intensive monitoring.
Change From Baseline for Number of Participants on the Modified WHO Ordinal Scale at Each Visit
A modified WHO ordinal scale was used for consistency with the recent study in adults hospitalized with severe COVID-19, to record the participant's status at the time of assessment. The modified WHO ordinal scale included the following levels :
1= Not hospitalized, no limitations on activities; 2= Not hospitalized, limitation on activities; 3= Hospitalized, not requiring supplemental oxygen; 4= Hospitalized, requiring supplemental oxygen; 5= Hospitalized, on non-invasive ventilation or high-flow oxygen devices; 6= Hospitalized, on invasive mechanical ventilation or extra corporeal membrane oxygenation (ECMO); 7= Death. Higher scores mean worse outcome. Change from baseline for Number of Participants on the modified WHO ordinal scale was assesed.
Time to Improvement of at Least One Level Lower on the Modified WHO Ordinal Scale
Time to improvement is the time in which the participant sees a decrease after first study treatment in the WHO 7-point ordinal scale from baseline to a value at least one level lower in days (date of decrease in WHO scale - first dose date + 1). In the case that a patient has not decreased in the WHO scale at time of analysis or withdraws from the study before leaving the hospital, they would be censored at their date of last assessment in the data cut or early discontinuation date, respectively.
Time to Progression of at Least One Level Higher on the Modified WHO Ordinal Scale
Time to progression is the time in which the patient sees an increase after first study treatment in the WHO 7-point ordinal scale from baseline to a value at least one level higher in days (date of increase in WHO scale - first dose date + 1). In the case that a patient has not increased in the WHO scale at time of analysis or withdraws from the study before leaving the hospital, they would be censored at their date of last assessment in the data cut or early discontinuation date, respectively.
Number of Participants With Adverse Events
AEs (non-serious) as variables of safety and tolerability of RESP301 were assessed.
Severe AEs is defined as an event that prevents normal everyday activities. An AE that is assessed as severe should not be confused with an SAE. Severe is a category utilized for rating the intensity of an event; and both AE and SAE can be assessed as severe.
Time to Hospital Discharge
Time to hospital discharge is the time in the hospital after first study treatment in days (date of discharge - first dose date + 1). Patients who die before leaving the hospital would be considered failures (did not achieve hospital discharge) and censored. In the case that a patient is still hospitalized at time of analysis or withdraws from the study before leaving the hospital, they would be censored at their date of last assessment in the data cut or early discontinuation date, respectively.
Number of Participants With Mortality by Day 28
Incidence of mortality by Day 28 is the number of participants who have died by Day 28 and the percentage of patients reaching this endpoint will be summarized by treatment group.
Reduction in Oxygen Saturation (SpO2) to <90%
Room Air SpO2 for a summary of participants with reduction to < 90%, unless well clinically tolerated according to Investigator's opinion was assesed.
Events of Clinical Bronchial Hyper Responsiveness Related to Nebulization
Incidence of clinical bronchial hyper responsiveness related to nebulization was assessed. Oxygen saturation decreased and wheezing was assessed as an incidence of clinical bronchial hyper-responsiveness related to nebulization, requiring temporal increase of supplemental oxygen.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04460183
Brief Title
A Study to Assess Efficacy and Safety of RESP301 Plus Standard of Care (SOC) Compared to SOC Alone in Hospitalized Participants With COVID-19
Official Title
An Open-label, Adaptive Randomized, Controlled Multicenter Study to Evaluate the Efficacy and Safety of RESP301 Plus Standard of Care (SOC) Compared to SOC Alone in Hospitalized Participants With COVID-19 WHO Grade 3&4 (NOCoV2)
Study Type
Interventional
2. Study Status
Record Verification Date
April 2022
Overall Recruitment Status
Completed
Study Start Date
July 29, 2020 (Actual)
Primary Completion Date
April 24, 2021 (Actual)
Study Completion Date
May 21, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Thirty Respiratory Limited
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The effect of RESP301 as an add on treatment to SOC will be evaluated for its efficacy in reducing rate of progression to a more severe level of COVID-19 and for safety, by comparison with SOC alone in hospitalized COVID-19 patients.
Detailed Description
This is an open-label, randomized, multicenter, parallel group, concurrent, controlled study using a sequential adaptive design to evaluate the efficacy and safety of RESP301 plus SOC versus SOC alone in hospitalized patients with COVID-19 (World Health Organization [WHO] ordinal scale level 3 or 4).
Approximately 300 participants will be enrolled and randomized 2:1 to the Investigational arm or the Control arm. The study will be divided into the following periods: Screening period: (up to 2 days), Intervention (up to 10 days), follow-up (Day 14 and Day 28).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
COVID-19
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
19 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Investigational arm
Arm Type
Experimental
Arm Description
Participants will receive inhaled RESP301 administered using a nebulizer three times a day for up to 10 days in addition to the standard of care.
Arm Title
Control arm
Arm Type
Active Comparator
Arm Description
Participants will receive institutional SOC for the treatment of COVID-19
Intervention Type
Drug
Intervention Name(s)
RESP301, a Nitric Oxide generating solution
Intervention Description
Product application requires inhalation using a standard handheld nebulizer.
Intervention Type
Other
Intervention Name(s)
Standard of Care
Intervention Description
Participants will receive institutional SOC for the treatment of COVID-19.
Primary Outcome Measure Information:
Title
Number of Participants Who Progress by at Least One Level Higher on the Modified WHO Ordinal Scale
Description
A modified WHO ordinal scale was used for consistency with the recent study in adults hospitalized with severe COVID-19, to record the participant's status at the time of assessment. The modified WHO ordinal scale included the following levels :
1= Not hospitalized, no limitations on activities; 2= Not hospitalized, limitation on activities; 3= Hospitalized, not requiring supplemental oxygen; 4= Hospitalized, requiring supplemental oxygen; 5= Hospitalized, on non-invasive ventilation or high-flow oxygen devices; 6= Hospitalized, on invasive mechanical ventilation or extra corporeal membrane oxygenation (ECMO); 7= Death. Higher scores mean worse outcome. The number of participants that had an increase in at least one level higher score on the modified WHO ordinal scale was assessed.
Time Frame
Baseline, Day 2 and Day 3
Secondary Outcome Measure Information:
Title
Change in Room Air Oxygen Saturation (SpO2) From Baseline Over Time
Description
Pulse oximetry measurements were performed to evaluate SpO2. The effect of RESP301 as measured by room air SpO2 was assessed.
Time Frame
Day 1 (Baseline) Post-Nebulization, Day 2, 3, 4, 5, 6, and 7
Title
Change in National Early Warning Score (NEWS) 2 Symptom Score From Baseline Over Time
Description
The NEWS is based on a simple aggregate scoring system in which a score is allocated to physiological measurements, already recorded in routine practice, when patients present to, or are being monitored in hospital. Six simple physiological parameters form the basis of the scoring system: 1. Respiration rate; 2. Oxygen saturation; 3. Systolic blood pressure; 4. Pulse rate; 5. Level of consciousness or new confusion; 6. Temperature.
Each score is 0-3 and individual scores are added together for an overall score. An additional two points are added if the patient is receiving oxygen therapy. The total possible score ranges from 0 to 20. The higher the score the greater the clinical risk. Higher scores indicate the need for escalation, medical review and possible clinical intervention, and more intensive monitoring.
Time Frame
Day 1 (Baseline), Day 2, 3, 4, 5, 6, and 7
Title
Change From Baseline for Number of Participants on the Modified WHO Ordinal Scale at Each Visit
Description
A modified WHO ordinal scale was used for consistency with the recent study in adults hospitalized with severe COVID-19, to record the participant's status at the time of assessment. The modified WHO ordinal scale included the following levels :
1= Not hospitalized, no limitations on activities; 2= Not hospitalized, limitation on activities; 3= Hospitalized, not requiring supplemental oxygen; 4= Hospitalized, requiring supplemental oxygen; 5= Hospitalized, on non-invasive ventilation or high-flow oxygen devices; 6= Hospitalized, on invasive mechanical ventilation or extra corporeal membrane oxygenation (ECMO); 7= Death. Higher scores mean worse outcome. Change from baseline for Number of Participants on the modified WHO ordinal scale was assesed.
Time Frame
Day 1 (Baseline), Day 2, 3, 4, 5, 6, and 7
Title
Time to Improvement of at Least One Level Lower on the Modified WHO Ordinal Scale
Description
Time to improvement is the time in which the participant sees a decrease after first study treatment in the WHO 7-point ordinal scale from baseline to a value at least one level lower in days (date of decrease in WHO scale - first dose date + 1). In the case that a patient has not decreased in the WHO scale at time of analysis or withdraws from the study before leaving the hospital, they would be censored at their date of last assessment in the data cut or early discontinuation date, respectively.
Time Frame
From Baseline to Day 28
Title
Time to Progression of at Least One Level Higher on the Modified WHO Ordinal Scale
Description
Time to progression is the time in which the patient sees an increase after first study treatment in the WHO 7-point ordinal scale from baseline to a value at least one level higher in days (date of increase in WHO scale - first dose date + 1). In the case that a patient has not increased in the WHO scale at time of analysis or withdraws from the study before leaving the hospital, they would be censored at their date of last assessment in the data cut or early discontinuation date, respectively.
Time Frame
From Baseline to Day 28
Title
Number of Participants With Adverse Events
Description
AEs (non-serious) as variables of safety and tolerability of RESP301 were assessed.
Severe AEs is defined as an event that prevents normal everyday activities. An AE that is assessed as severe should not be confused with an SAE. Severe is a category utilized for rating the intensity of an event; and both AE and SAE can be assessed as severe.
Time Frame
From screening to safety follow up (Day 28)
Title
Time to Hospital Discharge
Description
Time to hospital discharge is the time in the hospital after first study treatment in days (date of discharge - first dose date + 1). Patients who die before leaving the hospital would be considered failures (did not achieve hospital discharge) and censored. In the case that a patient is still hospitalized at time of analysis or withdraws from the study before leaving the hospital, they would be censored at their date of last assessment in the data cut or early discontinuation date, respectively.
Time Frame
Day 10
Title
Number of Participants With Mortality by Day 28
Description
Incidence of mortality by Day 28 is the number of participants who have died by Day 28 and the percentage of patients reaching this endpoint will be summarized by treatment group.
Time Frame
Day 28
Title
Reduction in Oxygen Saturation (SpO2) to <90%
Description
Room Air SpO2 for a summary of participants with reduction to < 90%, unless well clinically tolerated according to Investigator's opinion was assesed.
Time Frame
Day 1 (Baseline), Day 2, Day 3
Title
Events of Clinical Bronchial Hyper Responsiveness Related to Nebulization
Description
Incidence of clinical bronchial hyper responsiveness related to nebulization was assessed. Oxygen saturation decreased and wheezing was assessed as an incidence of clinical bronchial hyper-responsiveness related to nebulization, requiring temporal increase of supplemental oxygen.
Time Frame
From screening to safety follow up (Day 28)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Participant has laboratory-confirmed SARS-CoV-2 infection as determined by reverse transcriptase polymerase chain reaction (RT-PCR) or other approved clinical testing prior to randomization.
Participant is hospitalized in relation to COVID-19, requiring supplemental oxygen to maintain SpO2 at a safe level (WHO level 3 & 4).
Participant is capable of giving signed informed consent
Participant is male or female. All females of childbearing potential, including pregnant females, must consent to urine pregnancy testing at screening to be eligible for the study.
Exclusion Criteria:
Rapidly deteriorating or likely to require escalation to high flow oxygen, invasive or non-invasive ventilatory support within 24 hours according to Investigator's opinion.
Unable to safely receive a nebulized treatment for approximately 8 minutes according to Investigator's opinion.
Unable to receive or considered ineligible for invasive or non-invasive ventilatory support.
History of methemoglobinemia.
Presence of uncontrolled asthma, history of severe bronchospasm.
Presence of severe chronic respiratory disease and tracheostomy.
Suspected or confirmed untreated, active tuberculosis.
Severely immune-compromised participants in Investigator's opinion.
Recent active coronary artery disease or decompensated heart failure.
Facility Information:
Facility Name
Imperial College Healthcare NHS Trust, St. Mary's Hospital
City
London
ZIP/Postal Code
W2 1NY
Country
United Kingdom
Facility Name
Royal Preston Hospital
City
Preston
ZIP/Postal Code
PR2 9HT
Country
United Kingdom
12. IPD Sharing Statement
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A Study to Assess Efficacy and Safety of RESP301 Plus Standard of Care (SOC) Compared to SOC Alone in Hospitalized Participants With COVID-19
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