Ultra-Protective Lung Ventilation With Extracorporeal CO2 Removal for Moderate ARDS

NCT04903262 | Recruiting DMC

• 1 other identifier: SUPERNOVA
• Study Type: interventional
• Target: 230
• Locations: 1 country
• Sites: 1

Brief Summary

Acute respiratory distress syndrome (ARDS) accounts for 10% of all ICU admissions and for 23% of patients requiring mechanical ventilation (MV). Its hospital mortality remains high, ranging from 34% in mild forms up to 46% in severe cases. Positive pressure MV remains the cornerstone of management, but at the same time it can contribute to worsening and maintenance of the lung injury when excessive stress and strain is applied to the lung parenchima (so-called ventilator-induced lung injury, VILI). VILI significantly contributes to the morbidity and mortality of ARDS patients, and it has been clearly demonstrated that protective (low-volume, low-pressure) MV settings are associated with a significant survival benefit. Unfortunately, in a certain proportion of ARDS cases, it is difficult to preserve acceptable gas exchange while maintaining protective ventilation settings, due to a high ventilatory load. In these cases, extracorporeal CO2 removal (ECCO2R) can be applied to grant the application of protective or even ultra-protective mechanical ventilation settings. The main outcome of this multicenter, prospective, randomized, comparative open trial is to determine whether early ECCO2R allowing ultraprotective mechanical ventilation improves the outcomes of patients with moderate ARDS.

Conditions

Acute Respiratory Distress Syndrome

Outcome Measures

Primary Outcomes (1)

• Number of ventilator-free days (VFDs) at 28 days after randomization.

  VFD to-day 28 is defined as the number of days of unassisted breathing to day 28 after randomization, assuming a patient survives for at least two consecutive calendar days after initiating unassisted breathing and remains free of assisted breathing.

  28 days

Secondary Outcomes (3)

• 28-day all-cause mortality

  28 days

• 90-day all-cause mortality

  90 days

• Cumulative incidence of severe adverse events during 28 days after randomization

  28 days

Study Arms (2)

ECCO2R

EXPERIMENTAL

Patients will be initially treated with "standardized ventilation": volume assist/control, VT = 6 mL/kg PBW; insp. flow 50-70 L/min, I:E ratio 1:1 to 1:3; RR 20-35 bpm; PEEP according to "low PEEP/ high FiO2" table. Goals: PaO2 55-80 mmHg or SpO2 88-95%; arterial pH: 7.30-7.45. ECCO2R initiated during "standardized ventilation" with blood flow between 1000 and 1500 mL/min. Anticoagulation with unfractionated heparin to a target aPTT of 1.5-2.0x baseline. Target: maintain PaCO2 at baseline ± 20%. VT initially reduced to 5 mL/kg. Sweep gas initiated and VT decreased to 4.5 then 4 mL/kg; PEEP adjusted to maintain same mean airway pressure as during "standardized ventilation", provided that Pplat ≤ 25 cmH2O. Respiratory rate decreased to 8 bpm. If PaCO2 \> 75 mmHg and/or pH \< 7.2, despite respiratory rate of 35/min and optimized ECCO2R, VT will be increased to the last previously tolerated VT. Recommendation: 2 daily lung recruitment maneuvers (as per clinical practice in each center).

Procedure: Ultraprotective ventilation with Extracorporeal CO2 removal

Standard of care

ACTIVE COMPARATOR

Patients will be treated with "standardized ventilation": volume assist/control, VT = 6 mL/kg PBW; insp. flow 50-70 L/min, I:E ratio 1:1 to 1:3; RR 20-35 bpm; PEEP according to "low PEEP/ high FiO2" table. Goals: PaO2 55-80 mmHg or SpO2 88-95%; arterial pH: 7.30-7.45. Recommendation: 2 daily lung recruitment maneuvers (as per clinical practice in each center).

Procedure: Conventional protective ventilation

Interventions

Ultraprotective ventilation with Extracorporeal CO2 removal PROCEDURE

HLS5.0 Cardiohelp® (Getinge Cardiopulmonary Care, Rastatt, Germany): 1.3 m² polymethylpentene hollow fiber membrane oxygenator. The extracorporeal blood flow is in the range of 1000 to 1500 mL/min. Sweep gas (air or oxygen) is drawn through the hollow fibers by a vacuum pump, creating a diffusion gradient for gas exchange across the membrane.

ECCO2R

Conventional protective ventilation PROCEDURE

Conventional lung protective mechanical ventilation, as described in the arm description ("standardized ventilation")

Standard of care

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years
• On invasive mechanical ventilation for ≤ 96 hours
• Presence of all of the following conditions for ≤ 24 hours: 100 \< PaO2/FiO2 ≤ 200 after 12 hours of "standardized ventilation" with PEEP ≥ 5; compliance of the respiratory system ≤ 0.5 ml/cmH2O per kg PBW; ventilatory ratio (VR) ≥ 1.5; bilateral opacities not fully explained by effusions, lobar/lung collapse, or nodules; respiratory failure not fully explained by cardiac failure or fluid overload

You may not qualify if:

• Pregnancy
• ARDS with PaO2/FiO2\<100 or PaO2/FiO2\>200 under standardized ventilation with PEEP ≥ 5 cmH2O
• Expected duration of mechanical ventilation \< 48 hours
• Severe COPD
• Chronic respiratory insufficiency with home ventilation or oxygen therapy
• Currently receiving ECMO therapy
• Acute brain injury
• Severe liver insufficiency (Child-Pugh scores \>7) or fulminant hepatic failure
• Heparin-induced thrombocytopenia
• Contraindication for systemic anticoagulation
• Platelet count \<50,000/mm3
• Prothrombin time-international normalized ratio (INR) \>1.5
• Patient moribund, decision to limit therapeutic interventions
• End-stage disease
• Unable to provide vascular access for ECCO2-R

Sponsors & Collaborators

• University of Bologna: lead
• Getinge Group: collaborator

Study Sites (1)

IRCCS AOUBO Policlinico di Sant'Orsola

Bologna, Italy

RECRUITING

MeSH Terms

Conditions

Respiratory Distress Syndrome

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Respiration Disorders

Study Officials

• Marco Ranieri, M.D.

  University of Bari

  STUDY CHAIR

• Antonio Pesenti, M.D.

  University of Milan

  STUDY CHAIR

Central Study Contacts

Tommaso Tonetti, M.D.

CONTACT

+39-0512143268; tommaso.tonetti@unibo.it

Marco Ranieri, M.D.

CONTACT

+39-0512143268; m.ranieri@unibo.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Full Professor

Study Record Dates

• First Submitted: May 21, 2021
• First Posted: May 26, 2021
• Study Start: December 1, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): March 31, 2027
• Last Updated: April 2, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)