Clinical trial NCT03245684: Assisted or Controlled Ventilation in Ards (Ascovent)
Official title: Assessment of the Inflammatory Response Associated With the Increase of Transpulmonary Pressure in Ipoxiemic Patients During Assisted Mechanical Ventilation
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: ARDS
Ventilator-Induced Lung Injury
Mechanical Ventilation Complication
Inflammatory Response
Keywords: ARDS
Ventilator-induced Lung Injury
cytokines
mechanical ventilation
Lead sponsor: University of Roma La Sapienza
Sponsor class: OTHER
First posted: 2017-08-10
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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)

Eligibility criteria: 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

Primary outcomes:
measure: Pulmonary concentration of inflammation mediators (broncho-alveolar lavage: BAL)
timeFrame: 96 hours
Secondary outcomes:
measure: Systemic concentration of inflammation mediators (plasma)
timeFrame: 96 hours
Other outcomes:
measure: Number of ventilator-free days (VFDs) during the 28 days immediately after randomization
timeFrame: 28 days
measure: Relationship between cytokine concentration and trans-pulmonary pressure
timeFrame: 96 hours
Locations:
Study officials:
References: