Closed Loop Ventilation With High Tidal Volumes and Safe Transpulmonary Pressure in COPD (COPD-SAFE) (COPD-SAFE)

Does Automatically Generated Tidal Volumes With Closed-loop Ventilation Leads to Safe Transpulmonary Pressures in Intubated Chronic Obstructive Pulmonary Disease Patients?

This study evaluates the safety and efficacy of high tidal volumes generated by "Adapted Support Ventilation (ASV) mode' in mechanically ventilated severe COPD patients. Every patient will be ventilated consecutively with ASV and Volume Control (VC) modes at 2 different levels of minute volume in 2 sets. ASV mode is expected to be safe measured by adequate inspiratory transpulmonary pressures and expected to be as effective as VC mode with lower intrinsic positive end expiratory pressure (iPEEP) levels.

Study Overview

• Status: Not yet recruiting
• Conditions: Chronic Obstructive Pulmonary Disease
• Intervention / Treatment: Other: Minute volume target of 100%; Other: Minute volume target to reach PaCO2 less than 45% (high tidal volume)

Detailed Description

Acute exacerbations of Chronic Obstructive Pulmonary Disease (COPD) may require mechanical ventilation. Various mechanical ventilation strategies and modes can be used to manage respiratory insufficiency in such patients. High tidal volumes required for mechanical ventilation of patients with obstructive pathologies is a well-known fact. Adapted Support Ventilation (ASV) is an intelligent closed-loop mechanical ventilation mode which automatically adjusts ventilation to lung mechanics. Led by measured lung mechanics, ASV mode often generates higher than usual tidal volumes during mechanical ventilation of COPD patients, particularly if the minute volume (MV) target is high. Thus, the effects of high tidal volumes on inspiratory transpulmonary pressure (Ptp), and whether Ptp stays within safe limits during ASV mode is of great interest.

Patients with acute exacerbation of COPD who required mechanical ventilation will be enrolled in the first 24 hours of admission to the intensive care unit. All patients will be deeply sedated. An esophageal balloon catheter will be inserted in order to measure transpulmonary pressure. 100 % minute volume target will be calculated in advance as 100 ml per ideal body weight.

Patients will be ventilated with two different MV targets in two sets. 'Adapted support ventilation' and 'volume control (VC)' modes will be used consecutively within each set. While the target minute volume will be 100 % in the first set, the volume target in the second set will be tuned to decrease patients PaCO2 below 45 mmHg. The sequence of ventilation mode will be randomized within each set. Ventilation periods will be 30 minutes with 15 minutes washout period in between. İf Ptp increase above 20 cmH20 at any ventilation mode, the tidal volume will be decreased.

ASV mode is expected to be safe, assessed by adequate inspiratory transpulmonary pressures, and expected to be as effective as VC mode with lower intrinsic positive end expiratory pressure (iPEEP) levels.

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Sami C Kirakli, MD; Phone Number: +905052352024; Email: samicenk.kirakli@sbu.edu.tr
• Study Contact Backup: Name: Burcu Acar Cinleti, MD; Phone Number: +905075022780; Email: burcu_acar911@yahoo.com

Study Locations

• Turkey
  • Yenisehir
    • Izmir, Yenisehir, Turkey, 35550
      • Izmir Dr. Suat Seren Chest Diseases and Surgery Education and Research Hospital, Intensive Care Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Acute exacerbation of Chronic Obstructive Lung Disease
• Being intubated for less than 24 hours
• Not being planned to be extubated in 24 hours
• Expiratory time constant (RCexp) more than > 2.0 s

Exclusion Criteria:

• Restrictive lung pathologies
• Impaired hemodynamic status
• Esophageal pathologies
• Bronchopleural fistula

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1.1. ASV, MV target 100%; Patients will be ventilated with ASV mode. Tidal volume, ventilation frequency, inspiratory duration will be automatically adjusted by the mechanical ventilator.	Other: Minute volume target of 100%; Patients will be ventilated to reach minute volume target of %100 (100 ml per ideal body weight).
Active Comparator: 1.2. Volume control, MV target %100; Patients will be ventilated with volume control mode. A tidal volume of 6-8 ml/kg will be used. I:E ratio will be set as 1:3 Ventilation frequency will be adjusted to reach the same volume target calculated in arm1.	Other: Minute volume target of 100%; Patients will be ventilated to reach minute volume target of %100 (100 ml per ideal body weight).
Experimental: 2.1. ASV, MV target to reach PaCO2< 45 mmHg; Patients will be ventilated with ASV mode. Tidal volume, ventilation frequency, inspiratory duration will be automatically adjusted by the mechanical ventilator.	Other: Minute volume target to reach PaCO2 less than 45% (high tidal volume); Patients will be ventilated to reach minute volume target associated with PaCO2 less than 45%.
Active Comparator: 2.2. Volume control, MV target to reach PaCO2< 45 mmHg; Patients will be ventilated with volume control mode. A tidal volume of 6-8 ml/kg will be used. I:E ratio will be set as 1:3. Ventilation frequency will be adjusted to reach the target PaCO2 level	Other: Minute volume target to reach PaCO2 less than 45% (high tidal volume); Patients will be ventilated to reach minute volume target associated with PaCO2 less than 45%.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Transpulmonary inspiratory pressure (Ptinsp)	Ptpinsp will be measured with an inspiratory pause maneuver.	30'th minute of each intervention arm

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intrinsic Positive End Expiratory Pressure (PEEPi)	PEEPi will be measured with an expiratory hold maneuver.	30'th minute of each intervention arm

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean arterial pressure	Mean arterial pressure measured by invasive or non-invasive methods	30'th minute of each intervention arm
PaO2, FiO2 ratio	Ratio of arterial partial oxygen pressure to inspired fraction of oxygen	30'th minute of each intervention arm
Heart rate	Heart rate measured by ECG	30'th minute of each intervention arm

Collaborators and Investigators

• Sponsor: Izmir Dr Suat Seren Chest Diseases and Surgery Education and Research Hospital

Publications and helpful links

General Publications

• Talmor D, Sarge T, Malhotra A, O'Donnell CR, Ritz R, Lisbon A, Novack V, Loring SH. Mechanical ventilation guided by esophageal pressure in acute lung injury. N Engl J Med. 2008 Nov 13;359(20):2095-104. doi: 10.1056/NEJMoa0708638. Epub 2008 Nov 11.
• Akoumianaki E, Maggiore SM, Valenza F, Bellani G, Jubran A, Loring SH, Pelosi P, Talmor D, Grasso S, Chiumello D, Guerin C, Patroniti N, Ranieri VM, Gattinoni L, Nava S, Terragni PP, Pesenti A, Tobin M, Mancebo J, Brochard L; PLUG Working Group (Acute Respiratory Failure Section of the European Society of Intensive Care Medicine). The application of esophageal pressure measurement in patients with respiratory failure. Am J Respir Crit Care Med. 2014 Mar 1;189(5):520-31. doi: 10.1164/rccm.201312-2193CI.
• Mauri T, Yoshida T, Bellani G, Goligher EC, Carteaux G, Rittayamai N, Mojoli F, Chiumello D, Piquilloud L, Grasso S, Jubran A, Laghi F, Magder S, Pesenti A, Loring S, Gattinoni L, Talmor D, Blanch L, Amato M, Chen L, Brochard L, Mancebo J; PLeUral pressure working Group (PLUG-Acute Respiratory Failure section of the European Society of Intensive Care Medicine). Esophageal and transpulmonary pressure in the clinical setting: meaning, usefulness and perspectives. Intensive Care Med. 2016 Sep;42(9):1360-73. doi: 10.1007/s00134-016-4400-x. Epub 2016 Jun 22.
• Grieco DL, Chen L, Brochard L. Transpulmonary pressure: importance and limits. Ann Transl Med. 2017 Jul;5(14):285. doi: 10.21037/atm.2017.07.22.

Study record dates

Study Major Dates

• Study Start (Anticipated): June 1, 2023
• Primary Completion (Anticipated): December 1, 2023
• Study Completion (Anticipated): March 1, 2024

Study Registration Dates

• First Submitted: September 11, 2019
• First Submitted That Met QC Criteria: September 12, 2019
• First Posted (Actual): September 13, 2019

Study Record Updates

• Last Update Posted (Estimate): May 5, 2023
• Last Update Submitted That Met QC Criteria: May 4, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Safety; Mechanical ventilation; Transpulmonary pressure; Intrinsic PEEP; Adaptive Support Ventilation
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: IGHCEAH-ICU-4

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No