Airway Pressure Release Ventilation for Moderate-to-severe Acute Respiratory Distress Syndrome

Acute Respiratory Distress Syndrome Clinical Trial

— EARL  

Official title:

Early Use of Airway Pressure ReLease Ventilation in Critically Ill Adults With Moderate-to-severe Acute Respiratory Distress Syndrome

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04156438
• Other study ID #: REB-19-51
• Status: Completed
• Phase: N/A
• Start date: June 29, 2020
• Est. completion date: December 31, 2021

Study information

• Verified date: January 2022
• Source: Saskatchewan Health Authority - Regina Area
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will examine the feasibility of a large clinical trial investigating the effectiveness of airway pressure release ventilation and low tidal volume ventilation for patients with moderate-to-severe acute respiratory distress syndrome.

Description:

Acute respiratory distress syndrome (ARDS) is a disease that has an incidence of 5% of hospitalized mechanically ventilated patients. ARDS is associated with high morbidity and mortality in critically ill patients, with mortality reported as high as 45% in severe ARDS. Patients who develop ARDS will require mechanical ventilation. Patients with ARDS are graded by the partial pressure of oxygen to fraction of inspired oxygen ratio (PaO2/FiO2) into three categories of severity: mild (PaO2/FiO2 201-300 mm Hg), moderate (PaO2/FiO2 101-200 mmHg), and severe (PaO2/FiO2 ≤ 100). Volutrauma and barotrauma are thought to contribute to the development of ARDS and alter mortality. The damage that occurs to the lungs manifests itself as inflammation, which leads to poor gas exchange of oxygen and carbon dioxide. Several strategies of lung-protective mechanical ventilation have been investigated in ARDS, including the use of low tidal volume ventilation (LTVV) or ARDSNet strategy, high frequency oscillation ventilation (HFOV), and airway pressure release ventilation (APRV). Lung protective strategies may be best beneficial prior to the onset of the development of ARDS or early in the course of the disease. As a result of the ARDSNet trial, LTVV has been adopted as the usual standard of care of ventilation and safest mode of ventilation for patients with ARDS. Recently, APRV has been proposed as a potential alternative to LTVV. APRV is a form of ventilation that keeps the lungs inflated through the majority of the breath cycle and allows patients to breathe spontaneously above this level of inflation. APRV allows for spontaneous respiration with increased airway pressure, potentially allowing for decreased sedation, shorter duration of mechanical ventilation, and decreased need for vasopressors. APRV has been associated with possible reduction in incidence of ARDS and in-hospital mortality in non-randomized observational studies. In patients with established ARDS, the use of APRV has also not been well studied, with most studies limited to small observational studies often with no comparison group. One randomized trial using APRV alone had less than 30% of patients having a diagnosis of ARDS and did not show any difference in any outcomes. Recently, Zhou and colleagues conducted a randomized trial comparing APRV to conventional ventilation in 138 mechanically ventilated patients with mild to severe ARDS and found that APRV may shorten the duration of mechanical ventilation and reduce intensive care unit (ICU) length of stay. While some of these studies had shown promise of APRV compared to LTVV, there has not been acceptance of APRV into guidelines as first line ventilation, and recommendations of institutions such as the Canadian Agency for Drugs and Technology in Health (CADTH) recommends interpreting these results with caution. Consequently, there remains clinical equipoise on this issue. Some ICU clinicians will currently use APRV as a rescue mode of ventilation in ARDS in their clinical practice while others will continue with the use of LTVV. We would like to randomize patients to LTVV or APRV and examine the feasibility of conducting a large multicentre randomized controlled trial in Canada.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1
• Est. completion date: December 31, 2021
• Est. primary completion date: December 31, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Fulfilling the diagnostic criteria of ARDS, according to the Berlin definition
• Moderate to severe ARDS as defined as a PaO2: FiO2 ratio of =150 during invasive mechanical ventilation
• Endotracheal intubation and mechanical ventilation for ARDS less than 48 hours

Exclusion Criteria:

• Age less than 18 years
• Pregnancy
• Intracranial hypertension (suspected or confirmed)
• Severe chronic obstructive pulmonary disease as defined by either:

1. FEV1/FVC less than 50% predicted, or

2. Chronic hypercarbia (PaCO2>45 mmHg), chronic hypoxemia (PaO2 < 55 mmHg) on room air, and/or elevated admission serum HCO3 >30 mmol/L

• Presence of documented barotrauma, i.e. pneumothorax
• Treatment with extracorporeal support (ECMO) at enrollment
• Refractory shock
• Advanced directives indicating preferences to not have advanced life support
• Moribund patient, i.e. not expected to survive longer than 24 hours

Related Conditions & MeSH terms

• Acute Lung Injury
• Acute Respiratory Distress Syndrome
• Respiratory Distress Syndrome
• Respiratory Distress Syndrome, Newborn
• Syndrome

Intervention

Device:
• Low tidal volume ventilation
Conventional ventilation strategy for patient with ARDS
• Airway pressure release ventilation
Experimental ventilation protocol for patients with ARDS

Locations

Country	Name	City	State
Canada	Regina General Hospital	Regina	Saskatchewan

Sponsors (1)

Lead Sponsor	Collaborator
Saskatchewan Health Authority - Regina Area

Country where clinical trial is conducted

Canada, 

References & Publications (18)

Acute Respiratory Distress Syndrome Network, Brower RG, Matthay MA, Morris A, Schoenfeld D, Thompson BT, Wheeler A. 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. 2000 May 4;342(18):1301-8. — View Citation

Andrews PL, Shiber JR, Jaruga-Killeen E, Roy S, Sadowitz B, O'Toole RV, Gatto LA, Nieman GF, Scalea T, Habashi NM. Early application of airway pressure release ventilation may reduce mortality in high-risk trauma patients: a systematic review of observational trauma ARDS literature. J Trauma Acute Care Surg. 2013 Oct;75(4):635-41. doi: 10.1097/TA.0b013e31829d3504. Review. — View Citation

ARDS Definition Task Force, Ranieri VM, Rubenfeld GD, Thompson BT, Ferguson ND, Caldwell E, Fan E, Camporota L, Slutsky AS. Acute respiratory distress syndrome: the Berlin Definition. JAMA. 2012 Jun 20;307(23):2526-33. doi: 10.1001/jama.2012.5669. — View Citation

Bellani G, Laffey JG, Pham T, Fan E, Brochard L, Esteban A, Gattinoni L, van Haren F, Larsson A, McAuley DF, Ranieri M, Rubenfeld G, Thompson BT, Wrigge H, Slutsky AS, Pesenti A; LUNG SAFE Investigators; ESICM Trials Group. Epidemiology, Patterns of Care, and Mortality for Patients With Acute Respiratory Distress Syndrome in Intensive Care Units in 50 Countries. JAMA. 2016 Feb 23;315(8):788-800. doi: 10.1001/jama.2016.0291. Erratum in: JAMA. 2016 Jul 19;316(3):350. JAMA. 2016 Jul 19;316(3):350. — View Citation

de Haro C, Martin-Loeches I, Torrents E, Artigas A. Acute respiratory distress syndrome: prevention and early recognition. Ann Intensive Care. 2013 Apr 24;3(1):11. doi: 10.1186/2110-5820-3-11. — View Citation

Ferguson ND, Cook DJ, Guyatt GH, Mehta S, Hand L, Austin P, Zhou Q, Matte A, Walter SD, Lamontagne F, Granton JT, Arabi YM, Arroliga AC, Stewart TE, Slutsky AS, Meade MO; OSCILLATE Trial Investigators; Canadian Critical Care Trials Group. High-frequency oscillation in early acute respiratory distress syndrome. N Engl J Med. 2013 Feb 28;368(9):795-805. doi: 10.1056/NEJMoa1215554. Epub 2013 Jan 22. — View Citation

Futier E, Constantin JM, Paugam-Burtz C, Pascal J, Eurin M, Neuschwander A, Marret E, Beaussier M, Gutton C, Lefrant JY, Allaouchiche B, Verzilli D, Leone M, De Jong A, Bazin JE, Pereira B, Jaber S; IMPROVE Study Group. A trial of intraoperative low-tidal-volume ventilation in abdominal surgery. N Engl J Med. 2013 Aug 1;369(5):428-37. doi: 10.1056/NEJMoa1301082. — View Citation

Gattinoni L, Pesenti A. The concept of "baby lung". Intensive Care Med. 2005 Jun;31(6):776-84. Epub 2005 Apr 6. — View Citation

Habashi NM. Other approaches to open-lung ventilation: airway pressure release ventilation. Crit Care Med. 2005 Mar;33(3 Suppl):S228-40. Review. — View Citation

Jain SV, Kollisch-Singule M, Sadowitz B, Dombert L, Satalin J, Andrews P, Gatto LA, Nieman GF, Habashi NM. The 30-year evolution of airway pressure release ventilation (APRV). Intensive Care Med Exp. 2016 Dec;4(1):11. doi: 10.1186/s40635-016-0085-2. Epub 2016 May 20. Review. — View Citation

Lim J, Litton E, Robinson H, Das Gupta M. Characteristics and outcomes of patients treated with airway pressure release ventilation for acute respiratory distress syndrome: A retrospective observational study. J Crit Care. 2016 Aug;34:154-9. doi: 10.1016/j.jcrc.2016.03.002. Epub 2016 Mar 9. — View Citation

Maxwell RA, Green JM, Waldrop J, Dart BW, Smith PW, Brooks D, Lewis PL, Barker DE. A randomized prospective trial of airway pressure release ventilation and low tidal volume ventilation in adult trauma patients with acute respiratory failure. J Trauma. 2010 Sep;69(3):501-10; discussion 511. doi: 10.1097/TA.0b013e3181e75961. — View Citation

Seal K, Featherstone R. Airway Pressure Release Ventilation for Acute Respiratory Distress Syndrome: Clinical Effectiveness and Guidelines [Internet]. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2018 Feb 1. Available from http://www.ncbi.nlm.nih.gov/books/NBK531787/ — View Citation

Serpa Neto A, Cardoso SO, Manetta JA, Pereira VG, Espósito DC, Pasqualucci Mde O, Damasceno MC, Schultz MJ. Association between use of lung-protective ventilation with lower tidal volumes and clinical outcomes among patients without acute respiratory distress syndrome: a meta-analysis. JAMA. 2012 Oct 24;308(16):1651-9. doi: 10.1001/jama.2012.13730. — View Citation

Sydow M, Burchardi H, Ephraim E, Zielmann S, Crozier TA. Long-term effects of two different ventilatory modes on oxygenation in acute lung injury. Comparison of airway pressure release ventilation and volume-controlled inverse ratio ventilation. Am J Respir Crit Care Med. 1994 Jun;149(6):1550-6. — View Citation

Walkey AJ, Summer R, Ho V, Alkana P. Acute respiratory distress syndrome: epidemiology and management approaches. Clin Epidemiol. 2012;4:159-69. doi: 10.2147/CLEP.S28800. Epub 2012 Jul 16. — View Citation

Young D, Lamb SE, Shah S, MacKenzie I, Tunnicliffe W, Lall R, Rowan K, Cuthbertson BH; OSCAR Study Group. High-frequency oscillation for acute respiratory distress syndrome. N Engl J Med. 2013 Feb 28;368(9):806-13. doi: 10.1056/NEJMoa1215716. Epub 2013 Jan 22. — View Citation

Zhou Y, Jin X, Lv Y, Wang P, Yang Y, Liang G, Wang B, Kang Y. Early application of airway pressure release ventilation may reduce the duration of mechanical ventilation in acute respiratory distress syndrome. Intensive Care Med. 2017 Nov;43(11):1648-1659. doi: 10.1007/s00134-017-4912-z. Epub 2017 Sep 22. — View Citation

* Note: There are 18 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Informed consent rate	A successful informed consent rate will be defined as =70% of substitute decision makers or patients approached choosing to participate in this trial	Informed consent rate will be measured over a 1 year period of the pilot study
Primary	Recruitment rate	A successful recruitment rate will be achieving at least 15 patients over the 1 year period.	Recruitment rate will be measured over the one year of the pilot study.
Primary	Protocol adherence rate	An adherence rate of at least 80% will be considered successful.	Protocol adherence will be measured for each study patient, and compiled over the duration of the pilot study (i.e. 1 year).
Secondary	28-day mortality	Death, measured from time of enrollment until 28 days.	Up to Day 28
Secondary	In-hospital mortality	Death, at hospital discharge	Up to 365 days
Secondary	ICU length of stay	Length of stay in the intensive care unit	Up to 365 days
Secondary	Hospital length of stay	Length of stay in the hospital in days	Up to 365 days
Secondary	Length/duration of mechanical ventilation	Length of time patient was on mechanical ventilation	Up to 365 days
Secondary	Incidence of tracheostomy	Incidence of tracheostomy during their ICU stay	Up to 365 days