Dataset Information

Protocol of a randomized controlled trial testing inhaled Nitric Oxide in mechanically ventilated patients with severe acute respiratory syndrome in COVID-19 (SARS-CoV-2).

ABSTRACT:

Introduction

Severe acute respiratory syndrome due to novel Coronavirus (SARS-CoV-2) 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 COVID-19. This is a multicenter randomized controlled trial with 1:1 individual allocation. Patients will be blinded to the treatment. Methods and analysis. 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. The primary outcome evaluates levels of oxygenation between the two groups at 48 hours. Secondary outcomes include rate of survival rate at 28 and 90 days in the two groups, time to resolution of severe hypoxemia, time to achieve negativity of SARS-CoV-2 RT-PCR tests. Ethics and dissemination. The study protocol has been approved by the Investigational Review Board of Xijing Hospital (Xian, China) and by the Partners Human Research Committee (Boston, USA). Recruitment will start after approval of both IRBs and local IRBs at other enrolling centers. Results of this study will be published in scientific journals, presented at scientific meetings, reported through flyers and posters, and published on related website or media in combating against this widespread contagious diseases.

Trial registration

Clinicaltrials.gov. NCT04306393.

SUBMITTER: Lei C

PROVIDER: S-EPMC7273302 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Publications

Protocol of a randomized controlled trial testing inhaled Nitric Oxide in mechanically ventilated patients with severe acute respiratory syndrome in COVID-19 (SARS-CoV-2).

Lei Chong C Su Binxiao B Dong Hailong H Bellavia Andrea A Fenza Raffaele Di RD Fakhr Bijan Safaee BS Gianni Stefano S Grassi Luigi Giuseppe LG Kacmarek Robert R Morais Caio Cesar Araujo CCA Pinciroli Riccardo R Vassena Emanuele E Berra Lorenzo L

medRxiv : the preprint server for health sciences 20200524

<h4>Introduction</h4>Severe acute respiratory syndrome due to novel Coronavirus (SARS-CoV-2) related infection (COVID-19) is characterized by severe ventilation perfusion mismatch leading to refractory hypoxemia. To date, there is no specific treatment available for COVID-19. 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 <i>invitro</i> and clinical evidence that inhaled n ...[more]

PMID: 32511534

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Project description:ObjectivesTo characterize contemporary use of inhaled nitric oxide in pediatric acute respiratory failure and to assess relationships between clinical variables and outcomes. We sought to study the relationship of inhaled nitric oxide response to patient characteristics including right ventricular dysfunction and clinician responsiveness to improved oxygenation. We hypothesize that prompt clinician responsiveness to minimize hyperoxia would be associated with improved outcomes.DesignAn observational cohort study.SettingEight sites of the Collaborative Pediatric Critical Care Research Network.PatientsOne hundred fifty-one patients who received inhaled nitric oxide for a primary respiratory indication.Measurements and main resultsClinical data were abstracted from the medical record beginning at inhaled nitric oxide initiation and continuing until the earliest of 28 days, ICU discharge, or death. Ventilator-free days, oxygenation index, and Functional Status Scale were calculated. Echocardiographic reports were abstracted assessing for pulmonary hypertension, right ventricular dysfunction, and other cardiovascular parameters. Clinician responsiveness to improved oxygenation was determined. One hundred thirty patients (86%) who received inhaled nitric oxide had improved oxygenation by 24 hours. PICU mortality was 29.8%, while a new morbidity was identified in 19.8% of survivors. Among patients who had echocardiograms, 27.9% had evidence of pulmonary hypertension, 23.1% had right ventricular systolic dysfunction, and 22.1% had an atrial communication. Moderate or severe right ventricular dysfunction was associated with higher mortality. Clinicians responded to an improvement in oxygenation by decreasing FIO2 to less than 0.6 within 24 hours in 71% of patients. Timely clinician responsiveness to improved oxygenation with inhaled nitric oxide was associated with more ventilator-free days but not less cardiac arrests, mortality, or additional morbidity.ConclusionsClinician responsiveness to improved oxygenation was associated with less ventilator days. Algorithms to standardize ventilator management may improve signal to noise ratios in future trials enabling better assessment of the effect of inhaled nitric oxide on patient outcomes. Additionally, confining studies to more selective patient populations such as those with right ventricular dysfunction may be required.

Project description:the current worldwide outbreak of Coronavirus disease 2019 (COVID-19) due to a novel coronavirus (SARS-CoV-2) is seriously threatening the public health. The number of infected patients is continuously increasing and the need for Intensive Care Unit admission ranges from 5 to 26%. The mortality is reported to be around 3.4% with higher values for the elderly and in patients with comorbidities. Moreover, this condition is challenging the healthcare system where the outbreak reached its highest value. To date there is still no available treatment for SARS-CoV-2. Clinical and preclinical evidence suggests that nitric oxide (NO) has a beneficial effect on the coronavirus-mediated acute respiratory syndrome, and this can be related to its viricidal effect. The time from the symptoms' onset to the development of severe respiratory distress is relatively long. We hypothesize that high concentrations of inhaled NO administered during early phases of COVID-19 infection can prevent the progression of the disease. This is a multicenter randomized controlled trial. Spontaneous breathing patients admitted to the hospital for symptomatic COVID-19 infection will be eligible to enter the study. Patients in the treatment group will receive inhaled NO at high doses (140-180 parts per million) for 30 minutes, 2 sessions every day for 14 days in addition to the hospital care. Patient in the control group will receive only hospital care. The primary outcome is the percentage of patients requiring endotracheal intubation due to the progression of the disease in the first 28 days from enrollment in the study. Secondary outcomes include mortality at 28 days, proportion of negative test for SARS-CoV-2 at 7 days and time to clinical recovery. The trial protocol has been approved at the Investigation Review Boards of Xijing Hospital (Xi'an, China) and The Partners Human Research Committee of Massachusetts General Hospital (Boston, USA) is pending. Recruitment is expected to start in March 2020. Results of this study will be published in scientific journals, presented at scientific meetings, and on related website or media in fighting this widespread contagious disease.

Dataset Information

Protocol of a randomized controlled trial testing inhaled Nitric Oxide in mechanically ventilated patients with severe acute respiratory syndrome in COVID-19 (SARS-CoV-2).

Introduction

Trial registration

Publications

Protocol of a randomized controlled trial testing inhaled Nitric Oxide in mechanically ventilated patients with severe acute respiratory syndrome in COVID-19 (SARS-CoV-2).

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