Ultraprotective Ventilation Without Extracorporeal Circulation During COVID 19 Pneumonia

NCT04349618 | Completed DMC

• 1 other identifier: 69HCL20_0322
• Study Type: interventional
• Target: 220
• Locations: 1 country
• Sites: 11

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.

Conditions

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

Keywords

COVID19; ARDS; MECHANICAL VENTILATION; ULTRAPROTECTIVE VENTILATION

Outcome Measures

Primary Outcomes (1)

• A composite score based on all-cause mortality and the number of ventilator free-days (VFD)

  For an alive patient at day 90, the score will be built as follow: a value +1 will be given for comparisons to dead patients and alive patients with a lower number of VFD. For comparisons to alive patients with a higher number of VFD a value -1 will be given and in case of identical number of VFD a value 0 will be given. For a dead patient a value -1 will be given for comparisons to alive patients and 0 for comparisons to dead patients. For a given patients the score will correspond to the sum of values resulting to the comparison to all patients of the other group. A higher score indicates a more favorable result.

  Day 90

Secondary Outcomes (17)

• All-cause mortality (intention to treat)

  90-day after inclusion

• Ventilator-free days (VFD)

  day 60 after inclusion

• All-cause mortality with per protocol analysis

  90-day

• Time to successful extubation

  60 days

• Length of hospital stay

  90 days

Study Arms (2)

PROTECTIVE VENTILATION

ACTIVE COMPARATOR

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

Other: PROTECTIVE VENTILATION

ULTRAPROTECTIVE VENTILATION

EXPERIMENTAL

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

Other: ULTRAPROTECTIVE VENTILATION

Interventions

PROTECTIVE VENTILATION OTHER

Protective ventilation with tidal volume 6 mL/kg of predicted body weight further adjusted to keep plateau pressure below 30 cm H2O and pH above 7.20, and PEEP set using the PEEP FiO2 table of the ARMA trial

PROTECTIVE VENTILATION

ULTRAPROTECTIVE VENTILATION OTHER

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, and PEEP set using the PEEP FiO2 table of the ARMA trial

ULTRAPROTECTIVE VENTILATION

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• patient under any extracorporeal CO2 removal technique or ECMO
• pneumothorax or bronchopleural fistula
• 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
• pregnancy, lactating women
• patient under a legal protective measure.
• lack of affiliation to social security as required by French regulation

Sponsors & Collaborators

• Hospices Civils de Lyon: lead

Study Sites (11)

Service de Médecine Intensive Réanimation CHU Gabriel Montpied

Clermont-Ferrand, 63003, France

Location

Service de Médecine Intensive Réanimation Hôpital Michallon - CHU Grenoble Alpes

La Tronche, 38700, France

Location

Service de Médecine Intensive Réanimation Hôpital Edouard Herriot Hospices Civils de Lyon

Lyon, 69003, France

Location

Service de Réanimation Chirurgicale Hôpital Edouard Herriot Hospices Civils de Lyon

Lyon, 69003, France

Location

Service de Médecine Intensive Réanimation Hôpital de la Croix Rousse Hospices Civils de Lyon

Lyon, 69004, France

Location

Service de Réanimation Chirurgicale Hôpital de la Croix Rousse Hospices Civils de Lyon

Lyon, 69004, France

Location

Service de réanimation Polyvalente Centre Hospitalier Saint Joseph-Saint Luc

Lyon, 69007, France

Location

Service de Réanimation Clinique de la Sauvegarde

Lyon, 69009, France

Location

Service de Réanimation Polyvalente Centre Hospitalier Lyon Sud Hospices Civils de Lyon

Pierre-Bénite, 69310, France

Location

Service de Réanimation Centre hospitalier Annecy Genevois

Pringy, 74374, France

Location

Service de Médecine Intensive Réanimation Hôpital Nord - CHU Saint-Etienne

Saint-Priest-en-Jarez, 42055, France

Location

Related Publications (2)

• Richard JC, Terzi N, Yonis H, Chorfa F, Wallet F, Dupuis C, Argaud L, Delannoy B, Thiery G, Pommier C, Abraham P, Muller M, Sigaud F, Rigault G, Joffredo E, Mezidi M, Souweine B, Baboi L, Serrier H, Rabilloud M, Bitker L; VT4COVID collaborators. Ultra-low tidal volume ventilation for COVID-19-related ARDS in France (VT4COVID): a multicentre, open-label, parallel-group, randomised trial. Lancet Respir Med. 2023 Nov;11(11):991-1002. doi: 10.1016/S2213-2600(23)00221-7. Epub 2023 Jul 12.

  PMID: 37453445 DERIVED

• 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.

  PMID: 34635128 DERIVED

MeSH Terms

Conditions

Respiratory Distress Syndrome; COVID-19; Pneumonia

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Respiration Disorders; Pneumonia, Viral; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 8, 2020
• First Posted: April 16, 2020
• Study Start: April 15, 2020
• Primary Completion: June 16, 2022
• Study Completion: June 16, 2022
• Last Updated: December 10, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

FR (11)