Ultra-Protective Lung Ventilation With Extracorporeal CO2 Removal for Moderate ARDS (SUPERNOVA)
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ClinicalTrials.gov Identifier: NCT04903262 |
Recruitment Status :
Not yet recruiting
First Posted : May 26, 2021
Last Update Posted : November 29, 2023
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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 Procedure: Conventional protective ventilation | Not Applicable |
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 : | June 1, 2024 |
Estimated Primary Completion Date : | December 31, 2025 |
Estimated Study Completion Date : | March 31, 2026 |
Arm | Intervention/treatment |
---|---|
Experimental: ECCO2R
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
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. |
Active Comparator: Standard of care
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
Conventional lung protective mechanical ventilation, as described in the arm description ("standardized ventilation") |
- 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.
- 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."
- 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".
- Cumulative incidence of severe adverse events during 28 days after randomization [ Time Frame: 28 days ]Device-related and/or patient-related severe adverse events
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Ages Eligible for Study: | 18 Years to 100 Years (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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; 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
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
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
Contact: Tommaso Tonetti, M.D. | +39-0512143268 | tommaso.tonetti@unibo.it | |
Contact: Marco Ranieri, M.D. | +39-0512143268 | m.ranieri@unibo.it |
Study Chair: | Marco Ranieri, M.D. | University of Bologna | |
Study Chair: | Antonio Pesenti, M.D. | University of Milan |
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: | November 29, 2023 |
Last Verified: | November 2023 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | No |
Studies a U.S. FDA-regulated Drug Product: | No |
Studies a U.S. FDA-regulated Device Product: | No |
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 |