Assisted or Controlled Ventilation in Ards (Ascovent) (ASCOVENT)

Assessment of the Inflammatory Response Associated With the Increase of Transpulmonary Pressure in Ipoxiemic Patients During Assisted Mechanical Ventilation

The present pilot randomized controlled clinical trial will test the hypothesis that in patients with ARDS, fixing ventilator settings to the conventional protective ventilatory strategy (VT 6 ml/kg ideal body weight and Pplat ≤ 30 cmH2O, PEEP according the PEEP/FiO2 table), control modes of mechanical ventilation will be associated to a concentration of pulmonary and systemic inflammatory mediators lower than the concentration of inflammatory mediators observed during assisted modes of mechanical ventilation.

Study Overview

• Status: Unknown
• Conditions: Inflammatory Response; ARDS; Ventilator-Induced Lung Injury; Mechanical Ventilation Complication
• Intervention / Treatment: Diagnostic test: assessment of inflammatory response during PSV

Detailed Description

All patients will be treated according to the sedation protocols and standards of care. Sedation will be guaranteed by continuous infusion of Propofol 2-4 ml / Kg / h, Remifentanil 0.05-0.1 mcg / Kg / min to obtain a RASS scale level of -5 of the RASS. Mio-resolution eventually obtained by a loading dose of 15 mg e.v. followed by a continuous infusion of 37.5 mg / h of besylated Cisatracury, will be reserved for patients with P/F <150.

During a 48 hrs pre-randomization period, control mechanical ventilation will be set with a Tidal Volume (VT) of 6 ml / kg (for ideal weight) and a Pplat limited to 30 cm H2O; inspiratory flow 50-70 l / min with end-of-breath pause of 0.2-0.5 sec, ratio I: E from 1: 1 to 1: 3, respiratory frequency of 20-35 steps to maintain 7.3 <pH <7.5. If the pH is <7.30 the respiratory frequency will increase up to 35 / min; If the pH is> 7.5, the respiratory rate will be progressively reduced to the target pH range. FiO2 and The PEEP will be set according to the ARDSnet table (33)

After 48 hours, the patient will be randomized through one of the following two groups:

Control Mechanical ventilation (CMV): patient's spontaneous activity will be shut done by sedation and/or respiratory muscles paralysis. Volume (during volume control) or pressure (during pressure control), PEEP, FiO2 and respiratory rate will be regulated according the ARDSnet protocol (33).

Pressure Support Ventilation (PSV): patient's spontaneous activity will maintained and sedation will be maintained at a level of Richmond Assessment Sedation Scale (RASS) between -2 and -3. The level of pressure support (including PEEP) will be limited to ≤ 30 cmH2O; the pressure support level will ensure a tidal volume of 6 ml / Kg ideal body weight. PEEP, FiO2 and respiratory rate will be regulated according the ARDSnet protocol (33)

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Not Applicable

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:

• Patients > 18 years of age who:

  1. Are intubated less than 24 hours since meeting the Berlin definition criteria for ARDS.
  2. Have a commitment to full support;
  3. Have no exclusion criteria

Exclusion Criteria:

1. Intubation and mechanical ventilation (any form) for > 24 hours;
2. Acute brain injury with Glasgow coma scale (GCS) <7;
3. Body mass index > 40;
4. Age < 18 years;
5. Neuromuscular disease that impairs ability to ventilate without assistance;
6. Severe chronic respiratory disease;
7. Burns > 40% total body surface area;
8. Malignancy or other irreversible disease or condition for which 6-month mortality is estimated to be greater than 50%;
9. Allogeneic bone marrow transplant within the last 5 years;
10. Chronic respiratory condition making patient respirator dependent;
11. Patient, surrogate, or physician not committed to full support;
12. Acute myocardial infarction or acute coronary syndrome within 30 days;
13. Moribund patient: not expected to survive 24 hours;
14. No consent/inability to obtain consent

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: Pressure Support Ventilation; after 48h of controlled ventilation the patient randomised in this arm will desedated and switched on Pressure Support Ventilation (PSV): patient's spontaneous activity will maintained and sedation will be maintained at a level of Richmond Assessment Sedation Scale (RASS) between -2 and -3. The level of pressure support (including PEEP) will be limited to ≤ 30 cmH2O; the pressure support level will ensure a tidal volume of 6 ml / Kg ideal body weight. PEEP, FiO2 and respiratory rate will be regulated according the ARDSnet protocol. assessment of inflammatory response during PSV	Diagnostic test: assessment of inflammatory response during PSV; assessment cytokines level in BAL and plasma
ACTIVE_COMPARATOR: Controlled Mechanical Ventilation; patient's spontaneous activity will be shut done by sedation and/or respiratory muscles paralysis. Volume (during volume control) or pressure (during pressure control), PEEP, FiO2 and respiratory rate will be regulated according the ARDSnet protocol	Diagnostic test: assessment of inflammatory response during PSV; assessment cytokines level in BAL and plasma

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pulmonary concentration of inflammation mediators (broncho-alveolar lavage: BAL)	Dosage of inflammatory mediators (tumor necrosis factor-α soluble receptors, interleukin-6, interleukin-8 and interleukin-1β and interleukin-1 receptor antagonist)	96 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Systemic concentration of inflammation mediators (plasma)	The concentrations of the same mediators (tumor necrosis factor-α soluble receptors, interleukin-6, interleukin-8 and interleukin-1β and interleukin-1 receptor antagonist) in a sample of 10 ml of blood taken from a central venous line will be analyzed	96 hours

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of ventilator-free days (VFDs) during the 28 days immediately after randomization		28 days
Relationship between cytokine concentration and trans-pulmonary pressure	End-expiratory and end-inspiratory occlusions will be performed. End-inspiratory Plateau Pressure. Pplat of the respiratory system (Pplatrs) will be the value of PAW after an end-inspiratory occlusion. End-inspiratory chest wall plateau pressure (PplatCW) will be measured as the variation in PES between end-expiratory and end-inspiratory occlusions; end-inspiratory plateau pressure of the lung (Pplatl) were estimated as Pplatrs - PplatCW	96 hours

Collaborators and Investigators

• Sponsor: University of Roma La Sapienza

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): September 1, 2017
• Primary Completion (ANTICIPATED): September 1, 2019
• Study Completion (ANTICIPATED): September 1, 2019

Study Registration Dates

• First Submitted: August 4, 2017
• First Submitted That Met QC Criteria: August 9, 2017
• First Posted (ACTUAL): August 10, 2017

Study Record Updates

• Last Update Posted (ACTUAL): August 10, 2017
• Last Update Submitted That Met QC Criteria: August 9, 2017
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Keywords: mechanical ventilation; ARDS; cytokines; Ventilator-induced Lung Injury
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Wounds and Injuries; Thoracic Injuries; Lung Injury; Ventilator-Induced Lung Injury
• Other Study ID Numbers: ASCOVENT

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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