Clinical trial NCT04667923: Noninvasive Ventilation in Moderate-to-severe COVID-19-associated Acute Respiratory Distress-syndrome
Official title: Noninvasive Ventilation in Moderate-to-severe COVID-19-associated Acute Respiratory Distress-syndrome to Prevent Tracheal Intubation: the COVID-NIV Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Covid19
ARDS
Lead sponsor: I.M. Sechenov First Moscow State Medical University
Sponsor class: OTHER
First posted: 2020-12-16
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: patients with COVID-19-associated moderate-to-severe acute respiratory distress-syndrome

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Intubation rate
timeFrame: On day 28
measure: Mortality
timeFrame: On day 28
Secondary outcomes:
measure: Change in arterial partial oxygen tension to inspiratory oxygen fraction (PaO2/FiO2) ratio
timeFrame: Days 1, 3, 5, 7, 10, 14, 21 during noninvasive ventilation
measure: Change in ventilatory ratio
timeFrame: Days 1, 3, 5, 7, 10, 14, 21 during noninvasive ventilation
measure: Change in alveolar dead space
timeFrame: Days 1, 3, 5, 7, 10, 14, 21 during noninvasive ventilation
measure: Change in tidal volume
timeFrame: Days 1, 3, 5, 7, 10, 14, 21 during noninvasive ventilation
measure: Change in accessory respiratory muscles workload
timeFrame: Days 1, 3, 5, 7, 10, 14, 21 during noninvasive ventilation
Other outcomes:
Locations:
city: Moscow
country: Russian Federation
facility: Sechenov University clinic #4
Study officials:
affiliation: Sechenov University
name: Andrey I Yaroshetskiy, MD, PhD, ScD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.