SARS (Severe Acute Respiratory Syndrome), Coronavirus
Conditions
Brief summary
Severe acute respiratory syndrome (SARS-CoV2) due to novel Coronavirus (2019-nCoV) related infection (COVID-19) is characterized by severe ventilation perfusion mismatch leading to refractory hypoxemia. To date, there is no specific treatment available for 2019-nCoV. Nitric oxide is a selective pulmonary vasodilator gas used in as a rescue therapy in refractory hypoxemia due to acute respiratory distress syndrome (ARDS). In-vitro and clinical evidence indicate that inhaled nitric oxide gas (iNO) has also antiviral activity against other strains of coronavirus. The primary aim of this study is to determine whether inhaled NO improves oxygenation in patients with hypoxic SARS-CoV2. This is a multicenter single-blinded randomized controlled trial with 1:1 individual allocation
Detailed description
Severe acute respiratory syndrome (SARS-CoV-2) due to novel Coronavirus (2019-nCoV) related infection (COVID-19) is characterized by severe ventilation perfusion mismatch leading to refractory hypoxemia. To date, there is no specific treatment available for 2019-nCoV. Nitric oxide is a selective pulmonary vasodilator gas used as a rescue therapy in refractory hypoxemia due to acute respiratory distress syndrome (ARDS). In has also shown in-vitro and clinical evidence that inhaled nitric oxide gas (iNO) has antiviral activity against other strains of coronavirus. The primary aim of this study is to determine whether inhaled NO improves oxygenation in patients with hypoxic SARS-CoV2. This is a multicenter randomized controlled trial with 1:1 individual allocation. Patients will be blinded to the treatment. Intubated patients admitted to the intensive care unit with confirmed SARS-CoV-2 infection and severe hypoxemia will be randomized to receive inhalation of NO (treatment group) or not (control group). Treatment will be stopped when patients are free from hypoxemia for more than 24 hours.
Interventions
DRUGNitric Oxide Gas
80 ppm of inhaled nitric oxide for 48 hours, followed by 40 ppm, followed by weaning before stop. Weaning criteria: maintenance of a PaO2/FiO2 ratio \>/= 300 for at least 24 hours consecutively.
Sponsors
Massachusetts General Hospital
Xijing Hospital
Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
Niguarda Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Masking description
The patient is blinded to the treatment.
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
(1) Adult patients, \>/= 18 year-old; (2) Patients admitted to the ICU; (3) Patients who are intubated and mechanically ventilated; (4) Confirmed diagnosis of SARS-CoV2 by positive rt-PCR.
Exclusion criteria
(1) Patients intubated for more than 72 hours from initiation of the treatment gas; (2) Subjects enrolled in another interventional research study; (3) 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; (4) Subjects with past medical history of lung malignancy or pneumonectomy or lung transplant; (5) Subjects receiving a tidal volume \< 3 cc/kg of ideal body weight at the time of enrollment; (6) Subjects with severe burns involving more than 40% of Total Body Surface Area; (7) Subjects that have experienced cardiac arrest with CPR for longer than 30 minutes; (8) Subjects with a presumed severe deficit in cerebral function with fixed dilated pupil; (9) Subjects receiving renal replacement therapy at the time of enrollment; (10) Subjects who have an impaired ability to ventilate without assistance; (11) Subjects who have a history of malignancy or other irreversible disease/conditions with a 6-month mortality \> 50%; (12) Subjects not fully committed to full support at the time of enrollment; (13) Subject receiving inhaled nitric oxide gas prior to enrollment; (14) Subject's hospital admission unrelated to COVID-19.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change of Arterial Oxygenation at 48 Hours From Enrollment | 48 hours | Difference within groups in terms of PaO2/FiO2 ratio. If a patient dies during the first 48 hours of treatment, the last available blood gas analysis will be used. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Reach Normoxemia During the First 28 Days After Enrollment | 28 days | Time to recover gas exchange to a PaO2/FiO2 =/\> 300 for at least 24 hours during the first 28 days after enrollment, within each group and comparison between groups. If the patient dies before day 28, the patient will be considered as "never recovered". |
| Proportion of SARS-nCoV-2 Free Patients During the First 28 Days After Enrollment | 28 days | Proportion of patients in each group who achieved a PaO₂/FiO₂ ratio \>300 for at least 24 consecutive hours during the first 28 days after enrollment. Patients who died before day 28 were classified as "never recovered." |
| Survival at 28 Days From Enrollment | 28 days | Proportion of patients surviving at 28 days within each group and comparison between groups. |
| Survival at 90 Days From Enrollment | 90 days | Proportion of patients surviving at 90 days within each group and comparison between groups. |
Countries
Sweden, United States
Contacts
STUDY_DIRECTORLorenzo Berra, MD
Massachusetts General Hospital
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 63 years |
| BMI | 30.2 kg/m^2 |
| Cerebrovascular disease | 8 Participants |
| Chronic Kidney Disease | 18 Participants |
| Connective Tissue disease | 1 Participants |
| COPD | 12 Participants |
| Dementia | 3 Participants |
| Diabetes | 39 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 30 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 67 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| History of malignancy | 7 Participants |
| History of myocardial infarction | 11 Participants |
| History of peptic ulcer | 4 Participants |
| Hypertension | 46 Participants |
| Immune Deficiency | 3 Participants |
| Liver disease | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 7 Participants |
| Race (NIH/OMB) Black or African American | 20 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 15 Participants |
| Race (NIH/OMB) White | 61 Participants |
| Sex: Female, Male Female | 31 Participants |
| Sex: Female, Male Male | 63 Participants |
| Smoking history Current Smoker | 4 Participants |
| Smoking history Former Smoker | 30 Participants |
| Smoking history Never Smoked | 49 Participants |
| Smoking history Unknown | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 32 / 94 | 32 / 99 |
| other Total, other adverse events | 0 / 94 | 0 / 99 |
| serious Total, serious adverse events | 0 / 94 | 0 / 99 |
Outcome results
None listed