Noninvasive Ventilation in Moderate-to-severe COVID-19-associated Acute Respiratory Distress-syndrome (COVID-NIV)

Noninvasive Ventilation in Moderate-to-severe COVID-19-associated Acute Respiratory Distress-syndrome to Prevent Tracheal Intubation: the COVID-NIV Study

Non-invasive ventilation can allow to avoid intubation and improve outcomes in moderate-to-severe COVID-19-associated acute respiratory distress-syndrome (ARDS). Data on NIV parameters adjustment based on expanded respiratory and gas exchange monitoring in COVID-19 associated ARDS is limited. Appropriate adjustment of the inspiratory positive airway pressure (IPAP) set as a point of the balance between minimal work of breathing (minimum point of W.Patrick scale for assessment of the accessory respiratory muscles and minimum diaphragm thickening fraction) and minimum tidal volume, and respiratory rate can decrease NIV failure in moderate-to-severe COVID-ARDS. The objective of the study is to evaluate the ability of non-invasive ventilation guided with expanded respiratory monitoring to decrease the intubation rate in in moderate-to-severe COVID-ARDS.

Study Overview

• Status: Completed
• Conditions: Covid19; ARDS
• Intervention / Treatment: Diagnostic test: Arterial blood gas; Diagnostic test: Respiratory monitoring; Diagnostic test: Respiratory muscles ultrasound; Diagnostic test: Electro impedance tomography; Diagnostic test: Capnography; Diagnostic test: Quasistatic pressure-volume curve

Detailed Description

In December 2019, an outbreak of a novel coronavirus emerged in Wuhan, China and rapidly spread worldwide. The World Health Organization (WHO) declared the outbreak a pandemic on March 11th, 2020. The clinical disease (COVID-19) results in critical illness in about 5% of patients with predominant acute respiratory failure.

The objective of the study is to evaluate the ability of non-invasive ventilation guided with expanded respiratory monitoring to decrease the intubation rate in in moderate-to-severe COVID-ARDS. Investigators will set IPAP as a point of the balance between minimal work of breathing (minimum point of W.Patrick scale for assessment of the accessory respiratory muscles, and minimum diaphragm thickening fraction) and minimum tidal volume, and respiratory rate. Investigators will set expiratory pressure at 8-10 cm of water and the inspiratory oxygen fraction (FiO2) to reach oxygen saturation by pulse oximetry (SpO2) 95%. All gas exchange measurements will be set at IPAP level. For gas exchange assessment investigators will measure partial oxygen tension in the arterial blood (PaO2), partial carbon dioxide tension in arterial blood (PaCO2), end-tidal carbon dioxide tension (PetCO2), then will calculate PAO2/FiO2, alveolar dead space (Vd alv) and ventilatory ratio (VR). Investigators will measure expiratory tidal volume (VT), respiratory rate (RR), peak inspiratory flow (PIF) and inspiratory time at 3 levels: at the set IPAP, at IPAP+4 cm of water and at IPAP-4 cm of water. Measurements will be repeated on day 1, 3, 5, 7, 14 and 21 of NIV. NIV failure is determined as one of the following at set IPAP 26 cm of water and FiO2 100%: fatigue, Patrick scale 5 points, SpO2<92%, apnoea, hemodynamic instability or Glasgow coma score <14 points.

In patients with NIV failure after intubation and every 7 day after intubation investigators will measure plateau pressure and calculate the driving pressure at PEEP 8-10-12-14 cm of water and VT 6 ml/kg predicted body weight (PBW), and VT+100 ml and VT+200 ml at PEEP 8 cm of water, plot static pressure volume-curve at positive end-expiratory pressure (PEEP) 5 and 14 cm of water, and perform electro impedance tomography.

This study is an observational trial in the ICU of the University hospital.

• Study Type: Observational
• Enrollment (Actual): 80

Contacts and Locations

Study Locations

• Russian Federation
  • Moscow, Russian Federation
    • Sechenov University Clinic #4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 76 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

patients with COVID-19-associated moderate-to-severe acute respiratory distress-syndrome

Description

Inclusion Criteria:

• at least one of the following criteria: fatigue, Patrick scale 5 points, SpO2<92% on standard oxygen therapy (<15 l/min) or continuous positive airway pressure (CPAP)-therapy with oxygen flow<15 l/min

Exclusion Criteria:

• pregnancy
• age less than 18 or more than 80 years
• life-threatening heart rhythm abnormalities and/or systolic blood pressure < 80 mmHg despite norepinephrine at a dose > 2 µg/kg/min
• primary lung diseases (e.g. interstitial lung diseases, lung emphysema) or tumour metastases in lungs
• chronic decompensated diseases with extrapulmonary organ dysfunction (tumour progression, liver cirrhosis, congestive heart failure)
• Glasgow cona score < 14
• inability to swallow
• upper airways obstruction

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intubation rate	Frequency of NIV failure	On day 28
Mortality	Mortality on day 28	On day 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in arterial partial oxygen tension to inspiratory oxygen fraction (PaO2/FiO2) ratio	Calculation of the arterial partial oxygen tension to inspiratory oxygen fraction (PaO2/FiO2) ratio using arterial oxygen tension measurement	Days 1, 3, 5, 7, 10, 14, 21 during noninvasive ventilation
Change in ventilatory ratio	Measurement of arterial carbon dioxide tension, minute ventilation and calculation of ventilatory ratio	Days 1, 3, 5, 7, 10, 14, 21 during noninvasive ventilation
Change in alveolar dead space	Calculation of the alveolar dead space using end-tidal carbon dioxide measurement and arterial carbon dioxide tension measurement	Days 1, 3, 5, 7, 10, 14, 21 during noninvasive ventilation
Change in tidal volume	Measurement of exhaled tidal volume	Days 1, 3, 5, 7, 10, 14, 21 during noninvasive ventilation
Change in accessory respiratory muscles workload	Calculation of the Patrick's scale (minimum 0 points, maximum 5 points, more points means worse outcome)	Days 1, 3, 5, 7, 10, 14, 21 during noninvasive ventilation

Collaborators and Investigators

• Sponsor: I.M. Sechenov First Moscow State Medical University
• Investigators: Principal Investigator: Andrey I Yaroshetskiy, MD, PhD, ScD, Sechenov University

Publications and helpful links

General Publications

• Agarwal R, Handa A, Aggarwal AN, Gupta D, Behera D. Outcomes of noninvasive ventilation in acute hypoxemic respiratory failure in a respiratory intensive care unit in north India. Respir Care. 2009 Dec;54(12):1679-87.
• Avdeev SN, Yaroshetskiy AI, Tsareva NA, Merzhoeva ZM, Trushenko NV, Nekludova GV, Chikina SY. Noninvasive ventilation for acute hypoxemic respiratory failure in patients with COVID-19. Am J Emerg Med. 2021 Jan;39:154-157. doi: 10.1016/j.ajem.2020.09.075. Epub 2020 Oct 1.
• Yaroshetskiy AI, Avdeev SN, Konanykhin VD. Acute Respiratory Distress Syndrome in COVID-19: Do All These Patients Definitely Require Intubation and Mechanical Ventilation? Am J Respir Crit Care Med. 2020 Nov 15;202(10):1480-1481. doi: 10.1164/rccm.202007-2713LE. No abstract available.
• Patrick W, Webster K, Ludwig L, Roberts D, Wiebe P, Younes M. Noninvasive positive-pressure ventilation in acute respiratory distress without prior chronic respiratory failure. Am J Respir Crit Care Med. 1996 Mar;153(3):1005-11. doi: 10.1164/ajrccm.153.3.8630538.
• Yaroshetskiy AI, Merzhoeva ZM, Tsareva NA, Trushenko NV, Nuralieva GS, Konanykhin VD, Krasnoshchekova AP, Avdeev SN. Breathing pattern, accessory respiratory muscles work, and gas exchange evaluation for prediction of NIV failure in moderate-to-severe COVID-19-associated ARDS after deterioration of respiratory failure outside ICU: the COVID-NIV observational study. BMC Anesthesiol. 2022 Oct 1;22(1):307. doi: 10.1186/s12871-022-01847-7.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2020
• Primary Completion (Actual): June 30, 2021
• Study Completion (Actual): August 31, 2021

Study Registration Dates

• First Submitted: December 11, 2020
• First Submitted That Met QC Criteria: December 12, 2020
• First Posted (Actual): December 16, 2020

Study Record Updates

• Last Update Posted (Actual): November 11, 2021
• Last Update Submitted That Met QC Criteria: November 10, 2021
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Respiration Disorders; Pneumonia, Viral; Pneumonia; Lung Diseases; Infant, Newborn, Diseases; Lung Injury; Infant, Premature, Diseases; COVID-19; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury
• Other Study ID Numbers: 002-NIV-COVID

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes