Risk Factors for Prolonged Invasive Mechanical Ventilation in COVID-19 Acute Respiratory Distress Syndrome

COVID-19 Clinical Trial

Official title:

Risk Factors for Prolonged Invasive Mechanical Ventilation in COVID-19 Acute Respiratory Distress Syndrome

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04411459
• Other study ID #: 273/2020/OSS/AUSLBO
• Status: Completed
• Start date: February 1, 2020
• Est. completion date: October 16, 2020

Study information

• Verified date: August 2021
• Source: Azienda Usl di Bologna
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This multicentric prospective clinical practice study aims at evaluating clinical factors associated with a prolonged invasive mechanical ventilation and other outcomes such as mortality and ICU length of stay in patients affected from COVID-19 related pneumonia and ARDS.

Description:

Background

On February 21th 2020, SARS-CoV-2 outbreak erupted in Italy and, in the immediately subsequent period, all the Italian regional Health Systems had to face with an overwhelming increase of COVID-19 admissions requiring isolation, oxygen, ventilation and ICU beds.

The COVID-19 related pneumonia presented as a particular entity in terms of clinical management and different ICUs adopt different clinical strategies, sometimes this is due to the local resources' availability. Mortality rate of the patients admitted to ICU is up to 26%.

To date, it is not clear which clinical, pharmacological and radiologic factors relate to a prolonged duration of mechanical ventilation, mortality and ICU length of stay and it's urgent to understand these aspects in order to develop optimal strategies to allow faster but safe paths for these patients.

Hypothesis and significance

SARS-CoV-2 related pneumonia ICU management is still undefined, in fact this entity seems to have clinical aspects rather different from other forms of interstitial pulmonary syndromes evolving in diffuse alveolar damage and many aspects related to ventilation such pulmonary compliance, driving pressure and response to pronation are very different from what traditionally observed from other forms of ARDS, moreover an abnormal trend towards hypercoagulability has been described in these patients.

Different treatments have been proposed and are under evaluation such as Tocilizumab, corticosteroids, hydroxychloroquine, antivirals, anticoagulants and antiplatelet therapies.

These treatments, together with common ICU practice aspects such as early/late tracheostomy, ventilatory parameters believed adequate in order to start a weaning procedure, fluidic balance, choice of analgesia and sedation regimens, are not standardized in this particular syndrome due to the lack of evidence available and there is need for information about which factors correlate to a lower duration of mechanical ventilation and mortality.

Collected data:

• Demographics and anamnesis: age, sex, weight, height, previous pathologies (Hypertension, Chronic ischemic heart disease, Chronic kidney disease, COPD, Diabetes, Chronic liver disease, active cancer, immunosuppressive therapy), smoker status, therapy with ACE-inhibitors, statins and Angiotensin II Receptor Blockers.

• Conditions at ICU admission: date of symptoms onset (fever and or cough), date of hospital admission, date of ICU admission, SOFA and SAPS II score, high flow nasal oxygen therapy before intubation, NIV/CPAP trial before intubation, duration of the NIV/CPAP trial, PaO2/FiO2 value before intubation, initial tidal volume set, initial PEEP set, Initial pplateau observed.

• Ventilation during the first 5 days: lowest PaO2/FiO2 value, ventilatory strategy (pressure control ventilation vs volume control ventilation and volumes), lowest static respiratory system compliance, highest driving pressure, highest PEEP, highest arterial pCO2 observed, number and duration of pronation cycles, response in terms of oxygenation to the first pronation, need for decapneization, use of nitric oxide, tracheostomy date, need for extracorporeal membrane oxygenation treatment.

• Pharmacologic strategies during the first 5 days: sedative regimen and maximum doses, neuromuscular blocking agents (type of NMBA and duration of continuous infusion).

• COVID specific therapies: antivirals (type, start and end date), chloroquine, tocilizumab (start date and route of administration), intravenous corticosteroids, other specific therapies.

• Other supportive therapies: first line antibacterial regimen, amines (maximum dose), renal replacement therapy, fluidic balance during the first 3 days after ICU admission, anticoagulation, antiaggregation.

• Complications during ICU stay:

• Cardiovascular (myocardial infarction, new onset supraventricular or ventricular arrhythmia, pulmonary embolism, pulmonary edema, haemorragic shock, cardiogenic shock, acute peripheral ischemia, pneumothorax)

• Neurologic (new onset ischemic stroke or cerebral haemorrage, critical illness polyneuropathy / myopathy, new onset seizures)

• Gastroenteric (gastrointestinal bleeding, severe diarrhea, intestinal occlusion, gastrointestinal perforation/ischemia)

• Extrapulmonary infections (documented blood steam, urinary tract, central nervous system, abdominal infection)

• Pulmonary infections after intubation (early onset VAP - < 7 days of mechanical ventilation, late onset VAP - ≥ 7 days of mechanical ventilation)

• Weaning from mechanical ventilation: last day of highest PEEP, first attempt of pressure support ventilation (PSV), P/F at the first attempt of PSV, entity of pressure support at the first attempt of PSV, PEEP at the first attempt of PSV, day of extubation, non-invasive ventilation or high flow oxygen therapy after extubation, first day of spontaneous breathing, need for reintubation and date

• Radiology: first available CT, last CT before ICU admission and intubation, last ICU follow-up CT. First available chest X ray, last chest X ray before ICU admission and intubation, last ICU- follow up chest X ray. 30 days follow-up CT (if available).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 470
• Est. completion date: October 16, 2020
• Est. primary completion date: June 30, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age = 18 years

• ICU admission because of the need of mechanical ventilation in the context of COVID-19 related pneumonia (swab proven)

Exclusion Criteria:

• COVID-19 related pneumonia complicating the clinical course of patients admitted to the ICU for another reason (e.g. trauma, stroke)

Related Conditions & MeSH terms

• Acute Lung Injury
• Complication of Treatment
• COVID-19
• Mechanical Ventilation
• Quality of Life
• Radiologic Increased Density of Lung
• Respiratory Distress Syndrome, Adult
• Respiratory Distress Syndrome, Newborn
• Sedation

Intervention

Other:
• Invasive mechanical ventilation
Invasive mechanical ventilation for respiratory failure associated to COVID-19 pneumonia

Locations

Country	Name	City	State
Italy	A.O. SS. Antonio, Biagio e Cesare Arrigo - Anestesia e Rianimazione	Alessandria
Italy	Anestesia e Rianimazione - Ospedale Civile di Baggiovara	Baggiovara
Italy	Ospedale Santa Maria Annunziata - Anestesia e Rianimazione	Bagno A Ripoli	FI
Italy	Anestesia e Rianimazione - Ospedale di Bentivoglio	Bentivoglio
Italy	Anestesia e Rianimazione - Ospedale Bellaria	Bologna
Italy	Anestesia e Rianimazione - Policlinico Universitario S.Orsola - Malpighi	Bologna
Italy	Anestesia e Terapia intensiva dei trapianti addominali e chirurgia epatobiliare - Policlinico Universitario S.Orsola - Malpighi	Bologna
Italy	Anestesia e Terapia Intensiva Polivalente - Policlinico Universitario S.Orsola - Malpighi	Bologna
Italy	Azienda Unità Sanitaria Locale	Bologna
Italy	Ospedale SS. Trinità - Anestesia e Rianimazione	Borgomanero
Italy	Anestesia e Rianimazione - Ospedale M. Bufalini	Cesena
Italy	Anestesia e Rianimazione - Ospedale degli Infermi	Faenza
Italy	Anestesia e Rianimazione Universitaria - Arcispedale Sant'Anna Ferrara	Ferrara
Italy	Anestesia e Rianimazione - Ospedale Morgagni - Pierantoni	Forlì
Italy	Anestesia e Rianimazione - Ospedale di Imola S.Maria della Scaletta	Imola
Italy	Ospedale Santo Stefano - Anestesia e Rianimazione	Prato
Italy	Anestesia e Rianimazione - Ospedale S. Maria delle Croci	Ravenna
Italy	Anestesia e Rianimazione - Arcispedale Santa Maria Nuova	Reggio Emilia
Italy	Anestesia e Rianimazione - Ospedale di Riccione	Riccione
Italy	Anestesia e Rianimazione - Ospedale Infermi	Rimini

Sponsors (2)

Lead Sponsor	Collaborator
Azienda Usl di Bologna	Lorenzo Gamberini

Country where clinical trial is conducted

Italy, 

References & Publications (5)

Bhatraju PK, Ghassemieh BJ, Nichols M, Kim R, Jerome KR, Nalla AK, Greninger AL, Pipavath S, Wurfel MM, Evans L, Kritek PA, West TE, Luks A, Gerbino A, Dale CR, Goldman JD, O'Mahony S, Mikacenic C. Covid-19 in Critically Ill Patients in the Seattle Region — View Citation

Gattinoni L, Chiumello D, Caironi P, Busana M, Romitti F, Brazzi L, Camporota L. COVID-19 pneumonia: different respiratory treatments for different phenotypes? Intensive Care Med. 2020 Jun;46(6):1099-1102. doi: 10.1007/s00134-020-06033-2. Epub 2020 Apr 14. — View Citation

Grasselli G, Zangrillo A, Zanella A, Antonelli M, Cabrini L, Castelli A, Cereda D, Coluccello A, Foti G, Fumagalli R, Iotti G, Latronico N, Lorini L, Merler S, Natalini G, Piatti A, Ranieri MV, Scandroglio AM, Storti E, Cecconi M, Pesenti A; COVID-19 Lomb — View Citation

Richardson S, Hirsch JS, Narasimhan M, Crawford JM, McGinn T, Davidson KW; the Northwell COVID-19 Research Consortium, Barnaby DP, Becker LB, Chelico JD, Cohen SL, Cookingham J, Coppa K, Diefenbach MA, Dominello AJ, Duer-Hefele J, Falzon L, Gitlin J, Haji — View Citation

Yehya N, Harhay MO, Curley MAQ, Schoenfeld DA, Reeder RW. Reappraisal of Ventilator-Free Days in Critical Care Research. Am J Respir Crit Care Med. 2019 Oct 1;200(7):828-836. doi: 10.1164/rccm.201810-2050CP. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Duration of mechanical ventilation and 28 days ventilator free days	Ventilator free days (VFDs) will be calculated in a time frame of 28 days, the beginning of observation will coincide with the day of intubation and observation will end after successful disconnection from mechanical ventilation.; For intubated patients, post extubation non invasive ventilation (NIV) will not be accounted as a ventilation period, in case of interval reintubation within 28 days, VFDs will be counted from the last successful extubation.; For tracheostomized patients, ventilator free days will be counted after successful disconnection from mechanical ventilation and interval reconnections will be considered in the ventilation interval as for intubated patients.	28 days
Secondary	ICU Mortality		60 days
Secondary	30 days survival after ICU discharge		30 days
Secondary	90 days survival after ICU discharge		90 days
Secondary	Quality of life at 90 days after ICU discharge measured with 15D instrument	15D instrument (http://www.15d-instrument.net/15d/) will be administered via telephonic interview; Areas assessed: MOBILITY, VISION, HEARING, BREATHING, SLEEPING, EATING, SPEECH, EXCRETION, USUAL ACTIVITIES, MENTAL FUNCTION, DISCOMFORT AND SYMPTOMS, DEPRESSION, DISTRESS, VITALITY, SEXUAL ACTIVITY	90 days
Secondary	Radiologic aspects - structured description of CT and RX data	First available CT, last CT before ICU admission and intubation, last ICU follow-up CT. First available chest X ray, last chest X ray before ICU admission and intubation, last ICU- follow up chest X ray and 30 days follow-up CT (if available) will be evaluated, if available.; Structured description; CT scan; Date: yyyy/mm/dd Parenchymal alterations: ground glass, crazy paving, parenchymal consolidation Extension: monolateral, bilateral Number of lobes involved: (1-5) Percentage of parenchymal involvement: 0-100% Distribution: subpleural, random, diffuse; X-ray scan; Date: yyyy/mm/dd Main aspects: normal, focal lesions, monolateral multifocal lesions (right/left), diffuse multifocal lesions Lesion aspects: interstitial, interstitial/alveolar, alveolar, consolidations Pleural effusion presence and entity; Pulmonary involvement score: 0 = no involvement; =< 25%; = 25-50% 3= 50-75%; 4 => 75% Total score (0-6): score of the right lung + score of the left lung	90 days
Secondary	Quality of life at 1 year after ICU discharge and persistent symptoms	15D instrument (http://www.15d-instrument.net/15d/) will be administered via telephonic interview; Areas assessed: MOBILITY, VISION, HEARING, BREATHING, SLEEPING, EATING, SPEECH, EXCRETION, USUAL ACTIVITIES, MENTAL FUNCTION, DISCOMFORT AND SYMPTOMS, DEPRESSION, DISTRESS, VITALITY, SEXUAL ACTIVITY; Persistent symptoms explored: Dyspnea measured with mMRC scale, palpitations, cough, arthromyalgia	1 year
Secondary	Radiologic aspects at 1 year CT scan	Presence and extension of pulmonary fibrosing and non fibrosing signs	1 year
Secondary	Pulmonary function tests at 1 year - FEV1%	FEV1% - Forced expiratory volume 1 second, % of predicted value referred to normative population	1 year
Secondary	Pulmonary function tests at 1 year - FVC%	FVC% - Forced vital capacity, % of predicted value referred to normative population	1 year
Secondary	Pulmonary function tests at 1 year - FEV1/FVC%	FEV1/FVC% - Forced expiratory volume 1 second/Forced Vital capacity, % of predicted value referred to normative population	1 year
Secondary	Pulmonary function tests at 1 year -	DLCO% - Diffusing capacity for carbon monoxide, % of predicted value referred to normative population	1 year