Strategies for Optimal Lung Ventilation in ECMO for ARDS: The SOLVE ARDS Study

Respiratory Distress Syndrome, Adult Clinical Trial

— SOLVE ARDS  

Official title:

Strategies for Optimal Lung Ventilation in ECMO for ARDS: The SOLVE ARDS Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01990456
• Other study ID #: SOLVE ARDS_01
• Status: Recruiting
• Phase: N/A
• First received: November 6, 2013
• Last updated: November 5, 2014
• Start date: September 2014

Study information

• Verified date: November 2014
• Source: University of Toronto
• Contact: Fan Eddy, MD, PhD
• Phone: +1 416 340 4800
• Email: Eddy.Fan[@]uhn.ca
• Is FDA regulated: No
• Health authority: Canada: Ethics Review Committee
• Study type: Interventional

Clinical Trial Summary

Due to lack of studies on mechanical ventilation strategies in patients with severe Acute Respiratory Distress Syndrome (ARDS) supported with Veno-Venous Extra-Corporeal Membrane Oxygenation (VV ECMO), ventilator settings in this patient population are set arbitrarily.

In this two-phases prospective, interventional, pilot study we hope to gain physiologically relevant data on two aspects of mechanical ventilation in patients with severe ARDS supported with VV ECMO: (1) the use of tidal ventilation and (2) the level of Positive End-Expiratory Pressure (PEEP).

1. PHASE 1: impact of tidal ventilation on VILI (10 patients) We hypothesized that a CPAP strategy that minimizes end-tidal pulmonary stress and strain mitigates VILI compared to the current mechanical ventilation practice that employs tidal ventilation in patients with severe ARDS on ECMO.

In this first phase we will test whether administering a distending inspiratory pressure to produce tidal ventilation is superior to a strategy where only continuous positive airway pressure (CPAP) is applied for ventilation induced lung injury (VILI) mitigation, as assessed by its impact on biotrauma (serum cytokines) and physiologic measurements.

2. PHASE 2: impact of PEEP on VILI (10 patients) We also hypothesized that adjusting PEEP to maximize respiratory system compliance reduces VILI in patients with severe ARDS on ECMO.

In the second phase we will therefore gain more insight as to whether a strategy that utilizes a PEEP level that correspond to best compliance is beneficial over Zero End-Expiratory Pressure (ZEEP). We will test the impact of both strategies on biotrauma (serum cytokines), physiologic parameters, and right ventricular function (transesophageal echocardiographic assessment).

Because ARDS patients supported with VV ECMO can be hemodynamically unstable, the use of imaging techniques that require transport, such as computed tomography, is limited. Therefore, bedside imaging techniques, such as pleural and lung ultrasound (PLUS) and focused bedside cardiac ultrasonography, are important tools for clinicians who care for these patients. This study will allow us to learn whether these techniques are feasible and valid in this patient population.

Furthermore, the knowledge gained from this study will allow us to assess the rationale and feasibility of performing a similar larger, randomized study in the future.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 16 Years and older

Eligibility

Inclusion Criteria:

• Severe ARDS (Berlin Definition)

• VV ECMO < 72 hours

• Endotracheal intubation or tracheostomy

Exclusion Criteria:

• Thoracic surgery/lung transplantation during the current hospitalization

• Contraindications to a RM (MAP < 60 mmHg despite administration of fluids and vasopressors; Active air leak through a thoracostomy tube; Pneumothorax, or subcutaneous or mediastinal emphysema, (if chest tube has not been inserted))

• Contraindications to TEE

• Age < 16 years

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Supportive Care

Related Conditions & MeSH terms

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

Intervention

Device:
• PHASE 1: impact of tidal ventilation on VILI
PHASE 1A - Baseline - Standard Ventilation Protocol (PCV 10 cmH2O, PEEP 10 cmH2O, RR 10, FiO2 0.30) PHASE 1B - CPAP Strategy - CPAP 10 cmH2O for 1 hour PHASE 1C - Higher Tidal Ventilation Strategy (PCV 20 cmH2O, PEEP 10 cmH2O, RR 10, FiO2 0.30) PHASE 1D - Return to Baseline - Standard Ventilation Protocol
• PHASE 2: impact of PEEP on VILI
PHASE 2A - Baseline - Standard Ventilation Protocol - (PCV 10 cmH2O, PEEP 10 cmH2O, RR 10, FiO2 0.30) PHASE 2B - Decremental PEEP Trial PHASE 2C - CPAP set at best compliance of respiratory system (as per decremental PEEP Trial) PHASE 2D - ZEEP PHASE 2E - Return to Baseline - Standard Ventilation Protocol

Locations

Country	Name	City	State
Canada	Medical Surgical ICU - Toronto General Hospital	Toronto	Ontario

Sponsors (3)

Lead Sponsor	Collaborator
University of Toronto	The Physicians' Services Incorporated Foundation, University Health Network, Toronto

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Ventilator-Induced Lung Injury (VILI) in patients with ARDS on ECMO ventilated with different strategies (tidal ventilation, CPAP, ZEEP), as measured by Serum Cytokines		1 hour after initiation of each experimental ventilation strategy	Yes
Secondary	Impact of a CPAP strategy (PEEP set at best compliance and at ZEEP) in patients with severe ARDS on ECMO, as measured by transesophageal echocardiography (TEE)	Quantification of RV function: RVEDA/LVEDA; LV end-diastolic/systolic eccentricity indexes: 2D RVFAC; TAPSE; Tissue Doppler-derived tricuspid lateral annular systolic velocity (S'); RIMP; 3D EF < 44%; Myocardial Acceleration During Isovolumic Contraction; Regional RV Strain	30 minutes after initiation of experimental CPAP/ZEEP strategy	No
Secondary	Feasibility and validity of focused cardiac ultrasound, as compared to TEE as gold standard, in the assessment of RV function in patients with ARDS on ECMO	Quantification of RV function: RVEDA/LVEDA; TAPSE; RV Annular Velocity (S'); LV end-diastolic and end-systolic eccentricity indexes	30 minutes after initiation of experimental CPAP/ZEEP strategy	No
Secondary	Feasibility of lung ultrasound in patients with severe ARDS on ECMO	Lung Ultrasound Score	30 minutes after initiation of experimental CPAP/ZEEP strategy	No
Secondary	Feasibility (patient recruitment, protocol adherence, physiologic tolerability)	This outcome will be assessed by: the ability to enrol the proposed patient sample within the timeframe of the study (24 months); >90% adherence to the experimental protocol on enrolled patients; >80% completion of the entire experimental protocol on enrolled patients	At overall study completion (i.e., 24 months from study start or after enrolment of last patient)	Yes