Strategy of UltraProtective Lung Ventilation With Extracorporeal CO2 Removal for New-Onset Moderate to seVere ARDS

NCT02282657 | Completed Phase 1

• 1 other identifier: SUPERNOVA
• Study Type: interventional
• Target: 95
• Locations: 1 country
• Sites: 1

Brief Summary

Pathophysiological, experimental and clinical data suggest that an '"ultraprotective" mechanical ventilation strategy may further reduce VILI and ARDS-associated morbidity and mortality. Severe hypercapnia induced by VT reduction in this setting might be efficiently controlled by ECCO2R devices. A proof-of-concept study conducted on a limited number of ARDS cases indicated that ECCO2R allowing VT reduction to 3.5-5 ml/kg to achieve Pplat\<25 cm H2O may further reduce VILI.

Conditions

Moderate Acute Respiratory Distress Syndrome

Keywords

extracorporreal; CO2 removal; ARDS; lung; Protective ventilation

Outcome Measures

Primary Outcomes (1)

• Achievement of VT reduction to 4 mL/kg while maintaining pH and PaCO2 to ± 20% of baseline values obtained at VT of 6 mL/kg.

  maximum 28 days

Secondary Outcomes (5)

• Assessment of the changes in pH/ PaO2 /PaCO2

  maximum 28 days

• Device CO2 clearance in the first 24 hours of ECCO2R

  maximum 28 days

• Amount of CO2 removed by the ECCO2R device

  maximum 28 days

• Evaluation of lung recruitment/derecruitment (FRC measurement by the ventilator, ECHO-LUS…)

  maximum 28 days

• The frequency of serious adverse events (SAE).

  maximum 28 days

Study Arms (1)

One single arm

EXPERIMENTAL

Procedure: Baseline ventilator settings will be established per the EXPRESS protocol: VT = 6 mL/kg (ideal body weight); inspiratory flow will be set at 50-70 L/min resulting in an end-inspiratory pause of 0.2-0.5 sec, I:E ratio 1:1 to 1:3, PEEP set so that the plateau pressure (Pplat), measured during the end-inspiratory pause of 0.2 to 0.5 s, will be within the following limits: 28 cm H2O ≤ Pplat ≤ 30 cm H2O; Set RR to 20-35 to maintain approximately the same minute ventilation as before study initiation. Baseline ventilator settings will be maintained for a 2-hour run-in time (time to setup ECCO2R devices). Use heated humidifiers for gas humidification and minimize instrumental dead space. ECCO2R will be initiated during the 2-hour run-in time. Neuromuscular blocking agents (NMBA) will be used. EtCO2 will be monitored. RR will be kept what it was at Baseline. Sweep gas flow will be adapted. Ventilation will be adapted. Respiratory rate will be adapted.

Device: ECCO2R will be initiated during the 2-hour run-in time; Other: Neuromuscular blocking agents (NMBA); Device: Ventilation; Other: Level of carbon dioxide released at the end of expiration; Other: Respiratory Rate; Other: Sweep gas flow; Other: Ventilation will be adapted; Other: Respiratory rate will be adapted

Interventions

ECCO2R will be initiated during the 2-hour run-in time DEVICE

A single (15.5 to 19 Fr) veno-venous ECCO2R catheter will be inserted percutaneously (jugular vein strongly suggested). Catheters should be rinsed with heparinized saline solution before insertion Once the catheter has been inserted each line will be filled with an heparinized saline solution before its connection to the extracorporeal circuit The ECCO2R circuit will be connected to the catheter and blood flow set, depending on the device, up to 1000 mL/min. Initially, sweep gas flow through the ECCO2R device will be set at zero (0 LPM) such as to not initiate CO2 removal through the device. Anticoagulation will be maintained with unfractionated heparin to a target aPTT of 1.5 - 2.0X baseline. A bolus of heparin is suggested at the time of cannulation.

One single arm

Neuromuscular blocking agents (NMBA) OTHER

Patients will receive NMBA starting in the run-in period and continued for the first 24 hours and thereafter will be directed by the attending physician

One single arm

Ventilation DEVICE

Following the 2-hour run-in time, VT will be reduced gradually to 5 mL/kg. Sweep gas initiated then VT decreased to 4.5 then 4 mL/kg and PEEP adjusted to reach 23 ≤ Pplat ≤ 25 cm H2O.

One single arm

Level of carbon dioxide released at the end of expiration OTHER

EtCO2 will be monitored for safety purposes. Blood gases will be analyzed 20-30 minutes after each VT reduction

One single arm

Respiratory Rate OTHER

RR will be kept what it was at baseline

One single arm

Sweep gas flow OTHER

Sweep gas flow will be adapted to maintain the same EtCO2

One single arm

Ventilation will be adapted OTHER

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.

One single arm

Respiratory rate will be adapted OTHER

If PaCO2 remains within the target range, respiratory rate will be progressively decreased to a minimum of 15/ min and facilitated by increases in sweep flow.

One single arm

Eligibility Criteria

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

You may qualify if:

• Mechanical ventilation with expected duration of \>24h
• Moderate ARDS according to the Berlin definition(16) PaO2/FiO2: 200-100 mmHg, with PEEP ≥ 5 cmH2O

You may not qualify if:

• Age \<18 years
• Pregnancy
• Decompensated heart insufficiency or acute coronary syndrome
• Severe COPD
• Major respiratory acidosis PaCO2\>60 mmHg
• Acute brain injury
• Severe liver insufficiency (Child-Pugh scores \>7) or fulminant hepatic failure
• Heparin-induced thrombocytopenia
• Contraindication for systemic anticoagulation
• Patient moribund, decision to limit therapeutic interventions
• Catheter access to femoral vein or jugular vein impossible
• Pneumothorax
• Platelet \<50 G/l

Sponsors & Collaborators

• European Society of Intensive Care Medicine: lead

Study Sites (1)

selected ICUs for the pilot phase

Different Locations and Several Countries, Belgium

Location

Related Publications (2)

• Dreyfuss D, Ricard JD, Saumon G, (2003) On the physiologic and clinical relevance of lung-borne cytokines during ventilator-induced lung injury. Am J Respir Crit Care Med 167: 1467-1471. Rouby JJ, Puybasset L, Nieszkowska A, Lu Q, (2003) Acute respiratory distress syndrome: lessons from computed tomography of the whole lung. Crit Care Med 31: S285-295. Dreyfuss D, Saumon G, (1998) Ventilator-induced lung injury: lessons from experimental studies. Am J Respir Crit Care Med 157: 294-323. Frank JA, Parsons PE, Matthay MA, (2006) Pathogenetic significance of biological markers of ventilator-associated lung injury in experimental and clinical studies. Chest 130: 1906-1914. The Acute Respiratory Distress Syndrome Network. (2000) Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med 342: 1301-1308. Terragni PP, Rosboch G, Tealdi A, Corno E, Menaldo E, Davini O, Gandini G, Herrmann P, Mascia L, Quintel M, Slutsky AS, Gattinoni L, Ranieri VM, (2007) Tidal hyperinflation during low tidal volume ventilation in acute respiratory distress syndrome. Am J Respir Crit Care Med 175: 160-166. Hager DN, Krishnan JA, Hayden DL, Brower RG, (2005) Tidal volume reduction in patients with acute lung injury when plateau pressures are not high. Am J Respir Crit Care Med 172: 1241-1245. Needham DM, Colantuoni E, Mendez-Tellez PA, Dinglas VD, Sevransky JE, Dennison Himmelfarb CR, Desai SV, Shanholtz C, Brower RG, Pronovost PJ, (2012) Lung protective mechanical ventilation and two year survival in patients with acute lung injury: prospective cohort study. BMJ 344: e2124. Feihl F, Eckert P, Brimioulle S, Jacobs O, Schaller MD, Melot C, Naeije R, (2000) Permissive hypercapnia impairs pulmonary gas exchange in the acute respiratory distress syndrome. Am J Respir Crit Care Med 162: 209-215.

  BACKGROUND

• Combes A, Fanelli V, Pham T, Ranieri VM; European Society of Intensive Care Medicine Trials Group and the "Strategy of Ultra-Protective lung ventilation with Extracorporeal CO2 Removal for New-Onset moderate to severe ARDS" (SUPERNOVA) investigators. Feasibility and safety of extracorporeal CO2 removal to enhance protective ventilation in acute respiratory distress syndrome: the SUPERNOVA study. Intensive Care Med. 2019 May;45(5):592-600. doi: 10.1007/s00134-019-05567-4. Epub 2019 Feb 21.

  PMID: 30790030 DERIVED

MeSH Terms

Interventions

Neuromuscular Blocking Agents; Respiratory Rate

Intervention Hierarchy (Ancestors)

Neuromuscular Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Vital Signs; Physical Examination; Diagnostic Techniques and Procedures; Diagnosis; Respiration; Respiratory Physiological Phenomena; Circulatory and Respiratory Physiological Phenomena

Study Officials

• Alain COMBES, PhD

  La pitié-Salpétrière Hospital

  PRINCIPAL INVESTIGATOR

• Marco RANIERI, PhD

  University of Turin S.Giovanni Battista Molinette Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 21, 2014
• First Posted: November 4, 2014
• Study Start: November 1, 2015
• Primary Completion: July 1, 2017
• Study Completion: July 30, 2017
• Last Updated: August 4, 2017

Record last verified: 2017-08

Locations

BE (1)