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S-Nitrosylation Therapy of COVID-19

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ClinicalTrials.gov Identifier: NCT04528771
Recruitment Status : Not yet recruiting
First Posted : August 27, 2020
Last Update Posted : August 27, 2020
Sponsor:
Collaborator:
Case Western Reserve University
Information provided by (Responsible Party):
Robert Schilz, University Hospitals Cleveland Medical Center

Brief Summary:
The primary objective of this study is to provide expanded access of S-nitrosylation therapy for the treatment of severe acute respiratory syndrome coronavirus (SARS-CoV2) infection.

Condition or disease Intervention/treatment Phase
SARS-CoV2 Infection Covid19 Drug: SNO Drug: Nitrogen gas Phase 1

Detailed Description:
Randomized controlled trial for safety of a 6-hour escalating dose of S-nitrosylation therapy or placebo to ventilated patients. This will be a single-site study conducted within the UH-CMC medical ICU designated COVID-19 quarantine areas.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 21 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Single-site double-blinded randomized placebo controlled trial with a non-inferiority design. The study will randomize 21 patients 2:1 to either S-nitrosylation therapy or placebo arms.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: The investigational product will be prepared and dispensed by designated unblinded site personnel at the pharmacy; the investigational product label will indicate the study number but will not indicate the treatment assignment. Any site personnel involved in the administration and assessment of the investigational product will be blinded to subject treatment assignments throughout the study.
Primary Purpose: Treatment
Official Title: Phase 1b Safety Trial for S-Nitrosylation Therapy to Treat COVID-19 Induced Respiratory Distress
Estimated Study Start Date : October 31, 2020
Estimated Primary Completion Date : March 31, 2021
Estimated Study Completion Date : April 30, 2021

Arm Intervention/treatment
Experimental: SNO
14 patients in the S-nitrosylation arm will receive SNO (six-hour treatment with a sequential increasing dose regimen of 20 ppm x 2 hr, 40 ppm x 2 hr, 80 ppm x 2 hr).
Drug: SNO
Six-hour SNO treatment by inhalation at a sequential increasing dose regimen of 20 ppm x 2 hr, 40 ppm x 2 hr, 80 ppm x 2 hr. Patient care and follow-up during and after ENO administration will follow the critical care clinical SOPs developed by our institution (attached in Additional Information), which are consistent with the guidelines set out by the World Health Organization.

Placebo Comparator: Placebo
7 patients in the placebo arm will receive nitrogen gas (six-hour treatment).
Drug: Nitrogen gas
Six-hour nitrogen gas treatment by inhalation.Patient care and follow-up during and after ENO administration will follow the critical care clinical SOPs developed by our institution (attached in Additional Information), which are consistent with the guidelines set out by the World Health Organization.
Other Name: Placebo




Primary Outcome Measures :
  1. Length of Hospital Stay [ Time Frame: 30 days ]
    Total hospitalization days: Hospitalization data will be collected from the EMR on Day 30. Treatment will follow the critical care clinical SOPs developed by our institution (attached in Additional Information), which are consistent with the guidelines set out by the World Health Organization.

  2. Number of Ventilator Days [ Time Frame: 30 days ]
    Total ventilator days:Ventilator Days will be recorded for each day through Day 30. The number of days on the ventilator will be counted and then used to calculate the number of ventilator free days. Days that subjects are weaning off and on the ventilator will be counted as days on the ventilator.

  3. Length of Intensive Care [ Time Frame: 30 days ]

    Total days in ICU: Intensive Care Unit Days will be recorded for each day through Day 30. Days will be counted in 24-hour periods, any partial days will be counted as a whole day. The level of ICU care needed will be recorded, based on clear definitions and specific clinical criteria in the covid-19 critical care procedure manual, as follows:

    • Level 1 - Mechanical ventilation and intensivist support. Patient is stable on lung protective equipment.
    • Level 2 - Advanced mechanical ventilation (capability to prone) and 24 hour intensivist support. Patient is hypoxic. Patient is stabilized on escalated ventilator settings (high PEEP, prone, etc.)
    • Level 3 - Advanced oxygenation/ventilation strategies, including ECMO and 24 intensivist support. Patient is severely hypoxic (ARDS), code status is discussed, palliative consult is discussed, RESP-ECMO parameters, and patient is ECMO candidate.

  4. All-Cause Mortality [ Time Frame: 30 days ]
    30-day all-cause mortality


Secondary Outcome Measures :
  1. Treatment Emergent Adverse Events [ Time Frame: 30 days ]
    Adverse events related to SNO therapy.

  2. Time to Respiratory Status Improvement [ Time Frame: 30 days ]

    Number of days required to see a greater than 2 point improvement on a 7-point respiratory status assessment ordinal scale.

    7-Point Respiratory Severity Scale Range: 1-7 Higher values = worse

    1. Not receiving oxygen supplementation; AND room air oxygen saturation ≥ 95%
    2. Supplemental oxygen ≤ 2 liters/min; OR room air oxygen saturation ≤ 94%
    3. Supplemental nasal oxygen >2 and <= 5 liters/min
    4. Supplemental nasal oxygen >5 liters/min
    5. HFNC or NIV with FiO2 > 50%
    6. Intubation or ECMO
    7. Death

  3. Clinical Status [ Time Frame: 30 days ]

    Proportion of patients in each stage at maximum severity on the 7-point clinical status assessment ordinal scale.

    Clinical status will be assessed using a 7-point ordinal scale as follows:

    1. Death
    2. Hospitalized, on invasive mechanical ventilation or ECMO
    3. Hospitalized, on non-invasive ventilation or high flow oxygen devices
    4. Hospitalized, requiring low flow supplemental oxygen
    5. Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise)
    6. Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care
    7. Not hospitalized

  4. Respiratory Clinical Status [ Time Frame: 30 days ]

    Respiratory clinical status assessed by a 7-point respiratory status ordinal scale that captures oxygen requirement, ventilator support or death.

    7-Point Respiratory Severity Scale Range: 1-7 Higher values = worse

    1. Not receiving oxygen supplementation; AND room air oxygen saturation ≥ 95%
    2. Supplemental oxygen ≤ 2 liters/min; OR room air oxygen saturation ≤ 94%
    3. Supplemental nasal oxygen >2 and <= 5 liters/min
    4. Supplemental nasal oxygen >5 liters/min
    5. HFNC or NIV with FiO2 > 50%
    6. Intubation or ECMO
    7. Death



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 89 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Hospitalized with confirmed SARS-CoV2 infection by polymerase chain reaction (PCR) or other validated tests as they become available.
  • In respiratory distress, defined as P/F ratio of < 200 mmHg.
  • 18-89 years of age.
  • Patients that are intubated and mechanically ventilated with a device approved/certified for the blending-in of other medical gases into the ventilator circuit.
  • Patients to be enrolled and to be able to start treatment within 36 h of being intubated.

Exclusion Criteria:

  • Covid-19 patients with mild to no respiratory distress, defined as P/F ratio > 200 mmHg.
  • Intubated Covid-19 patients ventilated with an FiO2 of > 0.90 (reduction of FiO2 at this level or higher when ENO is blended into the ventilation circuit cannot be avoided).
  • Patients that are ventilated with a device not certified for blending of other medical gases into the ventilator circuit.
  • Physician of record opposed to enrolling the patient due to perceived safety concerns; or any condition that does not allow the protocol to be followed safely.
  • Subjects with past medical history of lung malignancy or pneumonectomy or lung transplant
  • Subjects who have a history of malignancy or other irreversible disease/conditions with a 6-month mortality > 50%
  • Subjects that have experienced cardiac arrest with CPR for longer than 30 minutes
  • Pregnancy
  • Patients on extracorporeal membrane oxygenation (ECMO)
  • Patient groups at an increased risk to form methemoglobin. (e.g. congenital variants of Met-Hb)
  • Patients with anemia, defined as a hemoglobin of < 9 mg/dL

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04528771


Contacts
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Contact: Robert Schilz, DO, PhD 216-844-3201 robert.schilz@uhhospitals.org

Locations
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United States, Ohio
University Hospitals Cleveland Medical Center
Cleveland, Ohio, United States, 44106
Contact: Robert Schilz, DO, PhD    216-844-3201    robert.schilz@uhhospitals.org   
Contact: James Reynolds, PhD    (216) 368-5727    jxr343@case.edu   
Principal Investigator: Robert Schilz, DO, PhD         
Sub-Investigator: Rana Hejal, MD         
Sub-Investigator: Olivia Giddings, MD         
Sponsors and Collaborators
Robert Schilz
Case Western Reserve University
Investigators
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Principal Investigator: Robert Schilz, DO, PhD University Hospitals Cleveland Medical Center
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Responsible Party: Robert Schilz, Principal Investigator, University Hospitals Cleveland Medical Center
ClinicalTrials.gov Identifier: NCT04528771    
Other Study ID Numbers: STUDY20200453
First Posted: August 27, 2020    Key Record Dates
Last Update Posted: August 27, 2020
Last Verified: August 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Robert Schilz, University Hospitals Cleveland Medical Center:
respiratory distress
respiratory failure
Additional relevant MeSH terms:
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COVID-19
Respiratory Tract Infections
Infections
Pneumonia, Viral
Pneumonia
Virus Diseases
Coronavirus Infections
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Lung Diseases
Respiratory Tract Diseases