Clinical trial NCT04411459: Risk Factors for Prolonged Invasive Mechanical Ventilation in COVID-19 Acute Respiratory Distress Syndrome
Official title: Risk Factors for Prolonged Invasive Mechanical Ventilation in COVID-19 Acute Respiratory Distress Syndrome
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: COVID-19
Mechanical Ventilation
Quality of Life
Radiologic Increased Density of Lung
Sedation
Complication of Treatment
Keywords: COVID-19
Mechanical Ventilation
Quality of life
Complications during ICU stay
Lead sponsor: Azienda Usl di Bologna
Sponsor class: OTHER_GOV
Collaborators: name: Lorenzo Gamberini
First posted: 2020-06-02
Enrollment: 470
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: This study enrolls patients admitted to ICU needing intubation and mechanical ventilation bacause of respiratory failure for COVID-19 pneumonia without other primary causes for ICU admission

Brief 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.

Detailed 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).

Eligibility criteria: 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)

Primary outcomes:
measure: Duration of mechanical ventilation and 28 days ventilator free days
timeFrame: 28 days
Secondary outcomes:
measure: ICU Mortality
timeFrame: 60 days
measure: 30 days survival after ICU discharge
timeFrame: 30 days
measure: 90 days survival after ICU discharge
timeFrame: 90 days
measure: Quality of life at 90 days after ICU discharge measured with 15D instrument
timeFrame: 90 days
measure: Radiologic aspects - structured description of CT and RX data
timeFrame: 90 days
measure: Quality of life at 1 year after ICU discharge and persistent symptoms
timeFrame: 1 year
measure: Radiologic aspects at 1 year CT scan
timeFrame: 1 year
measure: Pulmonary function tests at 1 year - FEV1%
timeFrame: 1 year
measure: Pulmonary function tests at 1 year - FVC%
timeFrame: 1 year
measure: Pulmonary function tests at 1 year - FEV1/FVC%
timeFrame: 1 year
measure: Pulmonary function tests at 1 year -
timeFrame: 1 year
Other outcomes:
Locations:
city: Bagno A Ripoli
country: Italy
facility: Ospedale Santa Maria Annunziata - Anestesia e Rianimazione
state: FI
city: Alessandria
country: Italy
facility: A.O. SS. Antonio, Biagio e Cesare Arrigo - Anestesia e Rianimazione
city: Baggiovara
country: Italy
facility: Anestesia e Rianimazione - Ospedale Civile di Baggiovara
city: Bentivoglio
country: Italy
facility: Anestesia e Rianimazione - Ospedale di Bentivoglio
city: Bologna
country: Italy
facility: Azienda Unità Sanitaria Locale
city: Bologna
country: Italy
facility: Anestesia e Rianimazione - Ospedale Bellaria
city: Bologna
country: Italy
facility: Anestesia e Rianimazione - Policlinico Universitario S.Orsola - Malpighi
city: Bologna
country: Italy
facility: Anestesia e Terapia intensiva dei trapianti addominali e chirurgia epatobiliare - Policlinico Universitario S.Orsola - Malpighi
city: Bologna
country: Italy
facility: Anestesia e Terapia Intensiva Polivalente - Policlinico Universitario S.Orsola - Malpighi
city: Borgomanero
country: Italy
facility: Ospedale SS. Trinità - Anestesia e Rianimazione
city: Cesena
country: Italy
facility: Anestesia e Rianimazione - Ospedale M. Bufalini
city: Faenza
country: Italy
facility: Anestesia e Rianimazione - Ospedale degli Infermi
city: Ferrara
country: Italy
facility: Anestesia e Rianimazione Universitaria - Arcispedale Sant'Anna Ferrara
city: Forlì
country: Italy
facility: Anestesia e Rianimazione - Ospedale Morgagni - Pierantoni
city: Imola
country: Italy
facility: Anestesia e Rianimazione - Ospedale di Imola S.Maria della Scaletta
city: Prato
country: Italy
facility: Ospedale Santo Stefano - Anestesia e Rianimazione
city: Ravenna
country: Italy
facility: Anestesia e Rianimazione - Ospedale S. Maria delle Croci
city: Reggio Emilia
country: Italy
facility: Anestesia e Rianimazione - Arcispedale Santa Maria Nuova
city: Riccione
country: Italy
facility: Anestesia e Rianimazione - Ospedale di Riccione
city: Rimini
country: Italy
facility: Anestesia e Rianimazione - Ospedale Infermi
Study officials:
References:
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citation: Dalpiaz G, Gamberini L, Carnevale A, Spadaro S, Mazzoli CA, Piciucchi S, Allegri D, Capozzi C, Neziri E, Bartolucci M, Muratore F, Coppola F, Poerio A, Giampalma E, Baldini L, Tonetti T, Cappellini I, Colombo D, Zani G, Mellini L, Agnoletti V, Damiani F, Gordini G, Laici C, Gola G, Potalivo A, Montomoli J, Ranieri VM, Russo E, Taddei S, Volta CA, Scaramuzzo G. Clinical implications of microvascular CT scan signs in COVID-19 patients requiring invasive mechanical ventilation. Radiol Med. 2022 Feb;127(2):162-173. doi: 10.1007/s11547-021-01444-7. Epub 2022 Jan 16.
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