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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04903262
Recruitment Status : Not yet recruiting
First Posted : May 26, 2021
Last Update Posted : March 31, 2022
Sponsor:
Information provided by (Responsible Party):
V. Marco Ranieri, University of Bologna

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.


Condition or disease Intervention/treatment Phase
Acute Respiratory Distress Syndrome Procedure: Ultraprotective ventilation with Extracorporeal CO2 removal Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 230 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Strategy of Ultra-Protective Lung Ventilation With Extracorporeal CO2 Removal for New-Onset Moderate ARDS: A Prospective Multicenter Randomized Clinical Trial
Estimated Study Start Date : September 2022
Estimated Primary Completion Date : September 2024
Estimated Study Completion Date : December 2024


Arm Intervention/treatment
Experimental: ECCO2R
Patients will be treated with "standardized ventilation": constant flow, 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 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 value ± 20% of baseline settings with a VT = 6 mL/kg provided that pH remains ≥ 7.30. Following 2-hour run-in time, VT will be reduced to 5 mL/kg. Sweep gas will be initiated and VT decreased to 4.5 then 4 mL/kg, and PEEP adjusted to reach 23 ≤ Pplat ≤ 25 cmH2O. Respiratory rate progressively decreased to a minimum of 12 bpm (eventual increases in sweep gas flow). 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.
Procedure: Ultraprotective ventilation with Extracorporeal CO2 removal
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.

No Intervention: Standard of care
Patients will be treated with "standardized ventilation": constant flow, 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.



Primary Outcome Measures :
  1. Number of ventilator-free days (VFDs) at 28 days after randomization. [ Time Frame: 28 days ]
    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.


Secondary Outcome Measures :
  1. 28-day all-cause mortality [ Time Frame: 28 days ]
    All patients will be classified as either "alive at Study Day 28" or, if dead, "dead at Study Day 28."

  2. 90-day all-cause mortality [ Time Frame: 90 days ]
    All patients will be classified as either "alive at Study Day 90" or, if dead, "dead at Study Day 90".

  3. Cumulative incidence of severe adverse events during 28 days after randomization [ Time Frame: 28 days ]
    Device-related and/or patient-related severe adverse events



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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; bilateral opacities not fully explained by effusions, lobar/lung collapse, or nodules; respiratory failure not fully explained by cardiac failure or fluid overload

Exclusion Criteria:

  • 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
  • Acute coronary syndrome
  • Actual body weight exceeding 1 kg per centimeter of height
  • Burns > 40% total body surface
  • Bone marrow transplantation within the last 1 year

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04903262


Contacts
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Contact: Tommaso Tonetti, M.D. +39-0512143268 tommaso.tonetti@unibo.it
Contact: Marco Ranieri, M.D. +39-0512143268 m.ranieri@unibo.it

Sponsors and Collaborators
University of Bologna
Investigators
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Study Chair: Marco Ranieri, M.D. University of Bologna
Study Chair: Antonio Pesenti, M.D. University of Milan
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Responsible Party: V. Marco Ranieri, Full Professor, University of Bologna
ClinicalTrials.gov Identifier: NCT04903262    
Other Study ID Numbers: SUPERNOVA
First Posted: May 26, 2021    Key Record Dates
Last Update Posted: March 31, 2022
Last Verified: March 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Respiratory Distress Syndrome
Respiratory Distress Syndrome, Newborn
Acute Lung Injury
Lung Diseases
Respiratory Tract Diseases
Respiration Disorders
Infant, Premature, Diseases
Infant, Newborn, Diseases
Lung Injury