Ultraprotective Ventilation Without Extracorporeal Circulation During COVID 19 Pneumonia (VT4COVID)

Civil Hospices of Lyon

Status: Unknown

Conditions: Sars-CoV2; COVID19; Acute Respiratory Distress Syndrome; Pneumonia

Treatments: Other: PROTECTIVE VENTILATION; Other: ULTRAPROTECTIVE VENTILATION

Study type: Interventional

Funder types: Other

Identifiers

NCT04349618

69HCL20_0322

Details and patient eligibility

About

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.

Enrollment: 200 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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200 participants in 2 patient groups

PROTECTIVE VENTILATION

Active Comparator group

Description:

Protective ventilation with tidal volume 6 mL/kg of predicted body weight

Treatment:

Other: PROTECTIVE VENTILATION

ULTRAPROTECTIVE VENTILATION

Experimental group

Description:

Ultraprotective ventilation with tidal volume reduction down to 4 mL/kg further adjusted to keep plateau pressure below 30 cm H2O and pH above 7.20

Treatment:

Other: ULTRAPROTECTIVE VENTILATION