Rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART): Study protocol for a randomized controlled trial

Background: Acute respiratory distress syndrome (ARDS) is associated with high in-hospital mortality. Alveolar recruitment followed by ventilation at optimal titrated PEEP may reduce ventilator-induced lung injury and improve oxygenation in patients with ARDS, but the effects on mortality and other clinical outcomes remain unknown. This article reports the rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART). Methods/Design: ART is a pragmatic, multicenter, randomized (concealed), controlled trial, which aims to determine if maximum stepwise alveolar recruitment associated with PEEP titration is able to increase 28-day survival in patients with ARDS compared to conventional treatment (ARDSNet strategy). We will enroll adult patients with ARDS of less than 72 h duration. The intervention group will receive an alveolar recruitment maneuver, with stepwise increases of PEEP achieving 45 cmH(2)O and peak pressure of 60 cmH2O, followed by ventilation with optimal PEEP titrated according to the static compliance of the respiratory system. In the control group, mechanical ventilation will follow a conventional protocol (ARDSNet). In both groups, we will use controlled volume mode with low tidal volumes (4 to 6 mL/kg of predicted body weight) and targeting plateau pressure <= 30 cmH2O. The primary outcome is 28-day survival, and the secondary outcomes are: length of ICU stay; length of hospital stay; pneumothorax requiring chest tube during first 7 days; barotrauma during first 7 days; mechanical ventilation-free days from days 1 to 28; ICU, in-hospital, and 6-month survival. ART is an event-guided trial planned to last until 520 events (deaths within 28 days) are observed. These events allow detection of a hazard ratio of 0.75, with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. Discussion: If the ART strategy with maximum recruitment and PEEP titration improves 28-day survival, this will represent a notable advance to the care of ARDS patients. Conversely, if the ART strategy is similar or inferior to the current evidence-based strategy (ARDSNet), this should also change current practice as many institutions routinely employ recruitment maneuvers and set PEEP levels according to some titration method.Hospital do Coracao (HCor) as part of the Program 'Hospitais de Excelencia a Servico do SUS (PROADI-SUS)'Brazilian Ministry of Healt

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

IMPORTANCE The effects of recruitment maneuvers and positive end-expiratory pressure (PEEP) titration on clinical outcomes in patients with acute respiratory distress syndrome (ARDS) remain uncertain. OBJECTIVE To determine if lung recruitment associated with PEEP titration according to the best respiratory-system compliance decreases 28-day mortality of patients with moderate to severe ARDS compared with a conventional low-PEEP strategy. DESIGN, SETTING, AND PARTICIPANTS Multicenter, randomized trial conducted at 120 intensive care units (ICUs) from 9 countries from November 17, 2011, through April 25, 2017, enrolling adults with moderate to severe ARDS. INTERVENTIONS An experimental strategy with a lung recruitment maneuver and PEEP titration according to the best respiratory-system compliance (n = 501experimental group) or a control strategy of low PEEP (n = 509). All patients received volume-assist control mode until weaning. MAIN OUTCOMES AND MEASURES The primary outcomewas all-cause mortality until 28 days. Secondary outcomes were length of ICU and hospital stayventilator-free days through day 28pneumothorax requiring drainage within 7 daysbarotrauma within 7 daysand ICU, in-hospital, and 6-month mortality. RESULTS A total of 1010 patients (37.5% femalemean [SD] age, 50.9 [17.4] years) were enrolled and followed up. At 28 days, 277 of 501 patients (55.3%) in the experimental group and 251 of 509 patients (49.3%) in the control group had died (hazard ratio [HR], 1.2095% CI, 1.01 to 1.42P =.041). Compared with the control group, the experimental group strategy increased 6-month mortality (65.3% vs 59.9%HR, 1.1895% CI, 1.01 to 1.38P =.04), decreased the number of mean ventilator-free days (5.3 vs 6.4difference, -1.195% CI, -2.1 to -0.1P =.03), increased the risk of pneumothorax requiring drainage (3.2% vs 1.2%difference, 2.0%95% CI, 0.0% to 4.0%P =.03), and the risk of barotrauma (5.6% vs 1.6%difference, 4.0%95% CI, 1.5% to 6.5%P =.001). There were no significant differences in the length of ICU stay, length of hospital stay, ICU mortality, and in-hospital mortality. CONCLUSIONS AND RELEVANCE In patients with moderate to severe ARDS, a strategy with lung recruitment and titrated PEEP compared with low PEEP increased 28-day all-cause mortality. These findings do not support the routine use of lung recruitment maneuver and PEEP titration in these patients. (C) 2017 American Medical Association. All rights reserved.Brazilian Ministry of HealthBrazilian Ministry of HealthHCor Res Inst, Sao Paulo, BrazilUniv Sao Paulo, Cardiopulmonary Dept, Div Pulm, Heart Inst Incor, Sao Paulo, BrazilHosp Moinhos de Vento, Porto Alegre, RS, BrazilIrmandade Santa Casa Misericordia Porto Alegre, Porto Alegre, RS, BrazilFed Univ Sao Paulo UNIFESP, Anesthesiol Pain & Intens Care Dept, Sao Paulo, BrazilUniv Sao Paulo, Dept Epidemiol, Sch Publ Hlth, Sao Paulo, BrazilHosp Maternidade Sao Vicente Paulo, Barbalha, BrazilHosp Nereu Ramos, Florianopolis, SC, BrazilHosp Unimed Vitoria, Vitoria, BrazilHosp & Prontosocorro 28 Agosto, Manaus, Amazonas, BrazilUniv Sao Paulo, Unidade Emergencia Hosp Clin FMRP, Ribeirao Preto, BrazilHosp Estadual Dr Jayme Santos Neves, Serra, BrazilFundacao Univ Fed Grande Dourados, Univ Hosp, Dourados, BrazilUniv ICESI, Fdn Valle Lili, Dept Intens Care Med, Cali, ColombiaHosp Univ Oeste Parana, Cascavel, BrazilHosp Pablo Tobon Uribe, Medellin, ColombiaHosp Clin Porto Alegre, Porto Alegre, RS, BrazilHosp Reg Hans Dieter Schmidt, Joinville, BrazilUniv Malaya, Med Ctr, Kuala Lumpur, MalaysiaJagiellonian Univ, Med Coll, Dept Intens Care & Perioperat Med, Krakow, PolandHosp Nacl Alejandro Posadas, Moron, ArgentinaFed Univ Sao Paulo UNIFESP, Anesthesiol Pain & Intens Care Dept, Sao Paulo, BrazilWeb of Scienc

Rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART): Study protocol for a randomized controlled trial

Background: Acute respiratory distress syndrome (ARDS) is associated with high in-hospital mortality. Alveolar recruitment followed by ventilation at optimal titrated PEEP may reduce ventilator-induced lung injury and improve oxygenation in patients with ARDS, but the effects on mortality and other clinical outcomes remain unknown. This article reports the rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART). Methods/Design: ART is a pragmatic, multicenter, randomized (concealed), controlled trial, which aims to determine if maximum stepwise alveolar recruitment associated with PEEP titration is able to increase 28-day survival in patients with ARDS compared to conventional treatment (ARDSNet strategy). We will enroll adult patients with ARDS of less than 72 h duration. The intervention group will receive an alveolar recruitment maneuver, with stepwise increases of PEEP achieving 45 cmH(2)O and peak pressure of 60 cmH2O, followed by ventilation with optimal PEEP titrated according to the static compliance of the respiratory system. In the control group, mechanical ventilation will follow a conventional protocol (ARDSNet). In both groups, we will use controlled volume mode with low tidal volumes (4 to 6 mL/kg of predicted body weight) and targeting plateau pressure <= 30 cmH2O. The primary outcome is 28-day survival, and the secondary outcomes are: length of ICU stay; length of hospital stay; pneumothorax requiring chest tube during first 7 days; barotrauma during first 7 days; mechanical ventilation-free days from days 1 to 28; ICU, in-hospital, and 6-month survival. ART is an event-guided trial planned to last until 520 events (deaths within 28 days) are observed. These events allow detection of a hazard ratio of 0.75, with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. Discussion: If the ART strategy with maximum recruitment and PEEP titration improves 28-day survival, this will represent a notable advance to the care of ARDS patients. Conversely, if the ART strategy is similar or inferior to the current evidence-based strategy (ARDSNet), this should also change current practice as many institutions routinely employ recruitment maneuvers and set PEEP levels according to some titration method.13Hospital do Coracao (HCor) as part of the Program 'Hospitais de Excelencia a Servico do SUS (PROADI-SUS)'Brazilian Ministry of Healt