Clinical trial NCT04349618: Ultraprotective Ventilation Without Extracorporeal Circulation During COVID 19 Pneumonia
Official title: Open Label Randomized Controlled Trial of Ultraprotective Ventilation Without Extracorporeal Circulation in Patients With COVID 19 Pneumonia and Moderate to Severe ARDS
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Acute Respiratory Distress Syndrome
COVID19
Sars-CoV2
Pneumonia
Keywords: COVID19
ARDS
MECHANICAL VENTILATION
ULTRAPROTECTIVE VENTILATION
Lead sponsor: Hospices Civils de Lyon
Sponsor class: OTHER
First posted: 2020-04-16
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Mortality of COVID-19 pneumonia with acute respiratory distress syndrome (ARDS) is extremely high in preliminary reports amounting to 50-60%. Duration of mechanical ventilation in these patients appears to exceed standard duration of mechanical ventilation in non-COVID-19 ARDS patients, suggesting that COVID-19 patients may be particularly at risk for ventilator-induced lung injury. Treatment of COVID-19 ARDS patients is to date mainly supportive with protective mechanical ventilation (ventilation with low tidal volume (VT) i.e. 6 ml/kg of predicted body weight (PBW) and plateau pressure control below 30 cm H2O).

Mechanical ventilation with VT reduction below 6 ml/kg PBW in ARDS may reduce alveolar strain, driving pressure and hence ventilator-induced lung injury. Investigators recently performed a multicenter pilot study on 34 moderately severe to severe ARDS patients. This study demonstrated that ultraprotective ventilation with ultra-low VT (≤4.2 ml/kg PBW) without extracorporeal circulation may be applied in approximately 2/3 of the patients, with a 4 cmH2O median reduction in driving pressure, at the price of transient episodes of severe acidosis in approximately 1/3 of the patients. Investigators hypothesized that ultraprotective ventilation without extracorporeal circulation may reduce the mortality at day-90 and increase the number of days free from mechanical ventilation (VFD) at day-60, as compared to protective ventilation.


Eligibility criteria: Inclusion Criteria:

* Adults aged 18 years or older
* ARDS according to the Berlin definition
* COVID-19 pneumonia confirmed by RT-PCR
* Acute respiratory failure not fully explained by left ventricular failure or sodium overload
* Bilateral pulmonary radiological opacities not fully explained by pleural effusions or atelectasis or nodules
* Invasive mechanical ventilation with PaO2/FiO2 ≤ 150 mm Hg and PEEP ≥ 5 cm H2O with a tidal volume below or equal to 6 ml per kilogram of predicted body weight
* Continuous intravenous sedation as part of ARDS treatment

Exclusion Criteria:

* Exclusion criteria related to ARDS history

  * ARDS onset more than 48 hours before inclusion
  * previous inclusion in present study
* Exclusion criteria related to ARDS severity or complications

  * arterial pH \< 7.21 despite respiratory rate set to 35/min at the time of inclusion
  * patient under any extracorporeal CO2 removal technique or ECMO
  * pneumothorax or bronchopleural fistula
* Exclusion criteria related to comorbidities

  * suspected intracranial hypertension
  * severe chronic obstructive pulmonary disease defined by a GOLD score ≥ 3
  * chronic respiratory failure under home oxygen or non-invasive ventilation
  * chronic respiratory failure requiring long term oxygen or non-invasive ventilation
  * obesity with body weight over height ratio greater than 1 kg/cm
  * sickle cell disease
  * bone marrow transplant \< 6 months
  * burn injury with extension greater than 30% of body surface area
  * cirrhosis with Child-Pugh score C
  * advance directives to withhold or withdraw life sustaining treatment
* Exclusion criteria related to legislation

  * Patient under an exclusion period relative to participation to another clinical trial, or inclusion into a clinical trial interfering with the ventilatory strategies
  * pregnancy, lactating women
  * patient under a legal protective measure.
  * lack of affiliation to social security as required by French regulation
  * lack of written informed consent by patient or next of kin (unless if recourse to the emergency procedure in the absence of a loved one)

Primary outcomes:
measure: A composite score based on all-cause mortality and the number of ventilator free-days (VFD)
timeFrame: Day 90
Secondary outcomes:
measure: All-cause mortality (intention to treat)
timeFrame: 90-day after inclusion
measure: Ventilator-free days (VFD)
timeFrame: day 60 after inclusion
measure: All-cause mortality with per protocol analysis
timeFrame: 90-day
measure: Time to successful extubation
timeFrame: 60 days
measure: Length of hospital stay
timeFrame: 90 days
measure: Respiratory parameters assessed daily from inclusion to weaning of deep sedation or 14 days whichever comes first
timeFrame: 14 days
measure: Daily sedation dose during the first 14 days of the study
timeFrame: 14 days
measure: Rate of use of rescue therapies
timeFrame: 14 days
measure: Incidence density rate of severe mixed acidosis
timeFrame: ICU stay
measure: Incidence density rate of ventilator associated pneumonia
timeFrame: ICU stay
measure: Incidence density rate of acute cor pulmonale
timeFrame: ICU stay
measure: Incidence density rate of barotrauma
timeFrame: ICU stay
measure: Incidence density rate of any serious adverse events
timeFrame: ICU stay
measure: Cognitive impairment assessed by phone call using the Telephone Montreal Cognitive Assessment (T-MoCA) test
timeFrame: Day 365 after inclusion
measure: Quality of life assessed by the RAND 36-Item Health Survey (SF-36) score
timeFrame: Day 365 after inclusion
measure: Post-traumatic stress disorder assessed by the Impact of Event Scale - revised (IES-R) score by phone call
timeFrame: Day 365 after inclusion
measure: Cost-efficacy ratio of the innovative strategy compared to the reference strategy
timeFrame: Day 90 after inclusion
Other outcomes:
Locations:
city: Clermont-Ferrand
country: France
facility: Service de Médecine Intensive Réanimation CHU Gabriel Montpied
city: La Tronche
country: France
facility: Service de Médecine Intensive Réanimation Hôpital Michallon - CHU Grenoble Alpes
city: Lyon
country: France
facility: Service de Médecine Intensive Réanimation Hôpital Edouard Herriot Hospices Civils de Lyon
city: Lyon
country: France
facility: Service de Réanimation Chirurgicale Hôpital Edouard Herriot Hospices Civils de Lyon
city: Lyon
country: France
facility: Service de Médecine Intensive Réanimation Hôpital de la Croix Rousse Hospices Civils de Lyon
city: Lyon
country: France
facility: Service de Réanimation Chirurgicale Hôpital de la Croix Rousse Hospices Civils de Lyon
city: Lyon
country: France
facility: Service de réanimation Polyvalente Centre Hospitalier Saint Joseph-Saint Luc
city: Lyon
country: France
facility: Service de Réanimation Clinique de la Sauvegarde
city: Pierre-Bénite
country: France
facility: Service de Réanimation Polyvalente Centre Hospitalier Lyon Sud Hospices Civils de Lyon
city: Pringy
country: France
facility: Service de Réanimation Centre hospitalier Annecy Genevois
city: Saint-Priest-en-Jarez
country: France
facility: Service de Médecine Intensive Réanimation Hôpital Nord - CHU Saint-Etienne
Study officials:
References:
citation: Richard JC, Yonis H, Bitker L, Roche S, Wallet F, Dupuis C, Serrier H, Argaud L, Thiery G, Delannoy B, Pommier C, Abraham P, Muller M, Aubrun F, Sigaud F, Rigault G, Joffredo E, Mezidi M, Terzi N, Rabilloud M. Open-label randomized controlled trial of ultra-low tidal ventilation without extracorporeal circulation in patients with COVID-19 pneumonia and moderate to severe ARDS: study protocol for the VT4COVID trial. Trials. 2021 Oct 11;22(1):692. doi: 10.1186/s13063-021-05665-z.