ART - Alveolar Recruitment for Acute Respiratory Distress Syndrome Trial (ART)

Randomized Controlled Trial of Maximum Alveolar Recruitment Maneuver Plus Titrated PEEP Versus ARDSNet Strategy for ARDS

Acute respiratory distress syndrome (ARDS) is a common scenario in intensive care unit. Discussions about it is exponentially growing up due its high mortality rates all over the world and low quality of life among survivors. Mechanical ventilation is recognized to play an important role in treatment of patients with ARDS. However, mechanical ventilation itself has the potential to produce or worsen alveolar injury if inadequate strategies are chosen. Several studies compared different mechanical ventilation strategies in ARDS but the results remain uncertain regarding their influence on survival in patients with ARDS. Thus, this is a multicentric randomized controlled trial, with allocation concealment and intention to treat analysis to investigate if maximum alveolar recruitment maneuver in association to Positive end-expiratory pressure (PEEP) titrated by static compliance of respiratory system (ART strategy) is able to increase 28 days survival in patients with moderate to severe ARDS compared to conventional strategy proposed by the ARDS Clinical Network (ARDSNet strategy). Patients considered to this trial are those in mechanical ventilation with diagnosis of moderate to severe ARDS less than 72hours. Patients included will be randomized to receive ART strategy or ARDSNet strategy and will be followed until hospital discharge, 28 days and 6 months.

Study Overview

• Status: Completed
• Conditions: Respiratory Distress Syndrome, Adult
• Intervention / Treatment: Other: ART Strategy; Other: ARDSNet Strategy

• Study Type: Interventional
• Enrollment (Actual): 1013
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Brazil
  • SP
    • Sao Paulo, SP, Brazil, 04005-000
      • Hospital do Coracao

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• intubated, mechanically ventilated patients with diagnosis of moderate to severe ARDS less than 72 hours

Exclusion Criteria:

• age less than 18 years
• use of vasopressor drugs in increasing doses over the last 2 hours or mean arterial blood pressure less than 65mmHg
• presence of any contraindication to hypercapnia as intracranial hypertension or acute coronary syndrome
• pneumothorax, pneumomediastinum, subcutaneous emphysema or pneumatocele
• patient with no therapeutic perspective, candidates for palliative care exclusively
• patient previously randomized in the ART

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: ART Strategy; maximum alveolar recruitment plus PEEP titration	Other: ART Strategy; Maximum alveolar recruitment maneuver in association with PEEP titrated by the static compliance of respiratory system.
ACTIVE_COMPARATOR: ARDSNet Strategy; standard strategy (ARDSNet)	Other: ARDSNet Strategy; Conventional mechanical ventilation strategy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Survival in 28 days	Survival within 28 days from randomization	28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lenght of ICU stay	Length of hospital stay from randomization to ICU discharge	Maximum 6-months
Lenght of hospital stay	Length of hospital stay from randomization to hospital discharge	Maximum 6 months
Pneumothorax requiring drainage	We consider as pneumothorax requiring chest tube within 7 days any case that is possibly due to barotrauma, that is, we do not consider cases judged to be clearly caused by invasive procedures such as central venous punction or thoracocentesis.	7 days
Barotrauma	We consider as barotrauma within 7 days any pneumothorax, pneumomediastinum, subcutaneous emphysema or pneumatocele > 2cm detected on image exams between randomization and 7 days, except those judged to be clearly caused by invasive procedures.	7 days
Days free of mechanical ventilation	Number of days alive and out of mechanical ventilation between randomization and 28 days after randomization.	28 days
ICU survival	Survival at ICU discharge.	Maximum 6-months
In-hospital survival	Survival at hospital discharge.	Maximum 6-months
6-month survival	Survival within 6 months after randomization	6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Need of commencement/increase of vasopressors or hypotension (MAP < 65mmHg) in the first hour;	Need of commencement/increase of vasopressors or hypotension (MAP < 65mmHg) in the first hour after randomization.	1 hour
Hypoxemia (PaO2 < 55mmHg) in the first hour	Hypoxemia (PaO2 < 55mmHg) in the first hour after randomization	1 hour
Severe acidosis (pH < 7.10) in the first hour	Severe acidosis (pH < 7.10) in the first hour after randomization	1 hour
Cardiorespiratory arrest within 24 hours	Cardiorespiratory arrest defined as unexpected cardiac arrest, not due to progressive refractory shock within 24 hours after randomization.	24 hours
Deaths with refractory hypoxemia within 7 days	Death with refractory hypoxemia, defined as PaO2 < 55 mmHg in the last arterial blood gas analysis with FiO2 = 100%.	7 days
Death with refractory acidosis within 7 days	Death with refractory acidosis within 7 days, defined as pH ≤ 7.10 in the last arterial blood gas analysis	7 days
Death with barotrauma within 7 days	Death with barotrauma within 7 days after randomization. We consider as barotrauma any pneumothorax, pneumomediastinum, subcutaneous emphysema or pneumatocele > 2cm detected on image exams, except those judged to be clearly caused by invasive procedures.	7 days

Collaborators and Investigators

• Sponsor: Hospital do Coracao
• Investigators: Principal Investigator: Alexandre B Cavalcanti, MD, PhD, Hospital do Coracao; Study Chair: Carlos RR Carvalho, MD, PhD, Hospital do Coracao, Faculdade de Medicina da Universidade de Sao Paulo

Publications and helpful links

General Publications

• Zampieri FG, Costa EL, Iwashyna TJ, Carvalho CRR, Damiani LP, Taniguchi LU, Amato MBP, Cavalcanti AB; Alveolar Recruitment for Acute Respiratory Distress Syndrome Trial Investigators. Heterogeneous effects of alveolar recruitment in acute respiratory distress syndrome: a machine learning reanalysis of the Alveolar Recruitment for Acute Respiratory Distress Syndrome Trial. Br J Anaesth. 2019 Jul;123(1):88-95. doi: 10.1016/j.bja.2019.02.026. Epub 2019 Apr 5.
• Damiani LP, Berwanger O, Paisani D, Laranjeira LN, Suzumura EA, Amato MBP, Carvalho CRR, Cavalcanti AB. Statistical analysis plan for the Alveolar Recruitment for Acute Respiratory Distress Syndrome Trial (ART). A randomized controlled trial. Rev Bras Ter Intensiva. 2017 Apr-Jun;29(2):142-153. doi: 10.5935/0103-507X.20170024.
• Writing Group for the Alveolar Recruitment for Acute Respiratory Distress Syndrome Trial (ART) Investigators; Cavalcanti AB, Suzumura EA, Laranjeira LN, Paisani DM, Damiani LP, Guimaraes HP, Romano ER, Regenga MM, Taniguchi LNT, Teixeira C, Pinheiro de Oliveira R, Machado FR, Diaz-Quijano FA, Filho MSA, Maia IS, Caser EB, Filho WO, Borges MC, Martins PA, Matsui M, Ospina-Tascon GA, Giancursi TS, Giraldo-Ramirez ND, Vieira SRR, Assef MDGPL, Hasan MS, Szczeklik W, Rios F, Amato MBP, Berwanger O, Ribeiro de Carvalho CR. Effect of Lung Recruitment and Titrated Positive End-Expiratory Pressure (PEEP) vs Low PEEP on Mortality in Patients With Acute Respiratory Distress Syndrome: A Randomized Clinical Trial. JAMA. 2017 Oct 10;318(14):1335-1345. doi: 10.1001/jama.2017.14171.
• Morais CC, De Santis Santiago RR, Filho JR, Hirota AS, Pacce PH, Ferreira JC, Camargo ED, Amato MB, Costa EL. Monitoring of Pneumothorax Appearance with Electrical Impedance Tomography during Recruitment Maneuvers. Am J Respir Crit Care Med. 2017 Apr 15;195(8):1070-1073. doi: 10.1164/rccm.201609-1780LE. No abstract available.
• ART Investigators. Rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART): study protocol for a randomized controlled trial. Trials. 2012 Aug 28;13:153. doi: 10.1186/1745-6215-13-153.

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 1, 2011
• Primary Completion (ACTUAL): December 1, 2017
• Study Completion (ACTUAL): December 1, 2017

Study Registration Dates

• First Submitted: June 13, 2011
• First Submitted That Met QC Criteria: June 14, 2011
• First Posted (ESTIMATE): June 15, 2011

Study Record Updates

• Last Update Posted (ACTUAL): September 11, 2020
• Last Update Submitted That Met QC Criteria: September 9, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: Randomized Controlled Trial; Respiration, Artificial; Respiratory Distress Syndrome, Adult
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Disease; Infant, Newborn, Diseases; Lung Injury; Infant, Premature, Diseases; Syndrome; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury
• Other Study ID Numbers: CAAE - 0025.1.160.000-11