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Sigh in Acute Hypoxemic Respiratory Failure (PROTECTION)

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ClinicalTrials.gov Identifier: NCT03201263
Recruitment Status : Recruiting
First Posted : June 28, 2017
Last Update Posted : July 2, 2017
Sponsor:
Collaborators:
European Society of Intensive Care Medicine
University of Milan
University of Milano Bicocca
Information provided by (Responsible Party):
Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico

Brief Summary:

Mortality of intubated acute hypoxemic respiratory failure (AHRF) and acute respiratory distress syndrome (ARDS) patients remains considerably high (around 40%) (Bellani 2016). Early implementation of a specific mechanical ventilation mode that enhances lung protection in patients with mild to moderate AHRF and ARDS on spontaneous breathing may have a tremendous impact on clinical practice.

Previous studies showed that the addition of cyclic short recruitment maneuvers (Sigh) to assisted mechanical ventilation: improves oxygenation without increasing ventilation pressures and FiO2; decreases the tidal volumes by decreasing the patient's inspiratory drive; increases the EELV by regional alveolar recruitment; decreases regional heterogeneity of lung parenchyma; decreases patients' inspiratory efforts limiting transpulmonary pressure; improves regional compliances. Thus, physiologic studies generated the hypothesis that addition of Sigh to pressure support ventilation (PSV, the most common assisted mechanical ventilation mode) might decrease ventilation pressures and FiO2, and limit regional lung strain and stress through various synergic mechanisms potentially yielding decreased risk of VILI, faster weaning and improved clinical outcomes.

The investigators conceived a pilot RCT to verify clinical feasibility of the addition of Sigh to PSV in comparison to standard PSV.

The investigators will enrol 258 intubated spontaneously breathing patients with mild to moderate AHRF and ARDS admitted to the ICU.

Patients will be randomized through an online automatic centralized and computerized system to the following study groups (1:1 ratio):

  • PSV group: will be treated by protective PSV settings until day 28 or death or performance of spontaneous breathing trial (SBT);
  • PSV+Sigh group: will be treated by protective PSV settings with the addition of Sigh until day 28 or death or performance of spontaneous breathing trial (SBT).

Indications on ventilation settings, weaning, spontaneous breathing trial and rescue treatment will be specified.


Condition or disease Intervention/treatment Phase
Respiratory Failure Acute Respiratory Distress Syndrome Ventilator Lung Procedure: Sigh Procedure: Standard of care Not Applicable

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 258 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Randomised controlled trial, 2 groups, 1:1 randomisation
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: PRessure suppOrT vEntilation + Sigh in aCuTe hypoxemIc respiratOry Failure patieNts (PROTECTION): a Pilot Randomized Controlled Trial
Estimated Study Start Date : September 1, 2017
Estimated Primary Completion Date : September 1, 2018
Estimated Study Completion Date : September 1, 2019


Arm Intervention/treatment
Active Comparator: PSV group
Will be treated by standard of care for patients undergoing assisted mechanical ventilation (e.g., protective PSV settings, protocolized weaning, etc.).
Procedure: Standard of care
Standard of care

Experimental: PSV+Sigh group
Will be treated by standard of care for patients undergoing assisted mechanical ventilation (e.g., protective PSV settings, protocolized weaning, etc.) + Sigh (short cyclic recruitment breath once every minute) until death or spontaneous breathing trial and extubation.
Procedure: Sigh
Application of cyclic pressure control breath delivered at 30 cmH2O for 3 seconds once per minute in patients undergoing pressure support ventilation
Other Name: Short cyclic recruitment breath




Primary Outcome Measures :
  1. Clinical feasibility of PSV+Sigh vs. standard of carde (PSV) [ Time Frame: 2 years ]

    Feasibility will be assessed by measuring the number of patients in each group experiencing at least one of the following failure criteria:

    • switch to controlled ventilation following presence of predefined criteria;
    • use of PEEP ≥15 cmH2O, prone positioning, inhaled nitric oxide, extracorporeal membrane oxygenation;
    • re-intubation within 48 hours from extubation following predefined criteria.

    Based on previous data, the expected rate of failure in patients undergoing PSV will be 22% and we hypothesize a rate of 15% for patients in the PSV+Sigh group. Furthermore, we assume a non-inferiority of the treatment with PSV+Sigh, with a tolerance of 5%. Thus, a sample size of 258 patients (with 129 patients per study arm) will be sufficient to assess feasibility of the PSV+Sigh strategy in this pilot phase with power of 0.8 and alpha 0.05.



Secondary Outcome Measures :
  1. Clinical safety of PSV+Sigh comparing adverse events between 2 groups [ Time Frame: 2 years ]

    Compare incidence of the following adverse events in the 2 study groups:

    • hemodynamic instability with hypotension (i.e., SBP <90 mmHg) despite vasoactive drugs;
    • arrhythmias with heart rate <40 or >140 bpm;
    • radiographic evidence of barotrauma (i.e., pneumothorax, pneumomediastinum, pneumatocoele, or subcutaneous emphysema);
    • new chest tube placement.

  2. Quantification of the prevalence of Sigh responders [ Time Frame: 2 years ]
    Quantification of the prevalence of short- (i.e., within 30 minutes) and long-term (i.e., within 24 hours in the PSV+Sigh group) Sigh responders in respect to improved oxygenation.

  3. Mortality [ Time Frame: 2 years ]
    This analysis will be performed comparing the 2 study groups and in responders

  4. Ventilator-free days [ Time Frame: 2 years ]
    This analysis will be performed comparing the 2 study groups and in responders

  5. Number of days on assisted ventilation until day 28 [ Time Frame: 28 days ]
    This analysis will be performed comparing the 2 study groups and in responders

  6. Patients' comfort by visual analog scale [ Time Frame: 2 years ]
    This analysis will be performed comparing the 2 study groups and in responders



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • patients intubated since >24 hours and ≤7 days,
  • undergoing PSV since >4 and ≤24 hours,
  • PaO2/FiO2 ratio ≤300 mmHg (measured at clinical positive end-expiratory pressure [PEEP] and FiO2 values)
  • clinical PEEP ≥5 cmH2O,
  • Richmond Agitation-Sedation Scale (RASS) value of -2 to 0

Exclusion Criteria:

  • patients with PEEP ≥15 cmH2O;
  • PaCO2 >60 mmHg;
  • Arterial pH <7.30;
  • Age <18 year-old;
  • PaO2/FiO2 ratio ≤100 mmHg (measured at clinical PEEP and FiO2 values);
  • central nervous system or neuromuscular disorders;
  • history of severe chronic obstructive pulmonary disease or fibrosis;
  • AHRF fully explained by cardiac failure or fluid overload (e.g., left ventricle ejection fraction ≤40% with no other risk factor);
  • impossibility to titrate sedation to desired RASS value of -2 to 0;
  • evidence of active air leak from the lung (e.g., pneumothorax);
  • cardiovascular instability (e.g., systolic blood pressure [SBP] <90 mmHg despite vasopressors);
  • clinical suspect of elevated intracranial pressure;
  • extracorporeal support;
  • moribund status;
  • refusal by the attending physician.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03201263


Contacts
Contact: Tommaso Mauri, MD +390255033129 tommaso.mauri@unimi.it

Locations
China
Tiantan Hospital Active, not recruiting
Beijing, China
France
CHU Angers Not yet recruiting
Angers, France
Contact: Alain Mercat         
Principal Investigator: Alain Mercat         
Sub-Investigator: Francois Beloncle         
CHU Clermont-Ferrand Active, not recruiting
Clermont-Ferrand, France
Hospital de la croix rousse Active, not recruiting
Lyon, France
GH Sud Ile-de-France Active, not recruiting
Melun, France
Germany
UNIVERSITÄTSKLINIKUM Schleswig-Holstein Campus Kiel Active, not recruiting
Kiel, Germany
Greece
General hospital of Larissa Active, not recruiting
Lárisa, Greece
Italy
Ospedale di Catanzaro Pugliese Ciaccio Active, not recruiting
Catanzaro, Italy
Arcispedale Sant'Anna Recruiting
Ferrara, Italy
Contact: Carlo Alberto Volta         
Principal Investigator: Carlo A Volta         
Sub-Investigator: Savino Spadaro         
Ospedale San Martino Active, not recruiting
Genova, Italy
Ospedale Maggiore Policlinico Cà Granda Active, not recruiting
Milan, Italy, 20122
Istituto Clinico Humanitas Active, not recruiting
Milan, Italy
Ospedale L. Sacco Active, not recruiting
Milan, Italy
Ospedale Niguarda Active, not recruiting
Milan, Italy
Ospedale San Gerardo Active, not recruiting
Monza, Italy
Ospedale Gemelli Active, not recruiting
Rome, Italy
Spain
Vall d'Hebron Not yet recruiting
Barcelona, Spain
Contact: Oriol Roca         
Principal Investigator: Oriol Roca         
Sub-Investigator: M Garcia         
Foundacion J Diaz Active, not recruiting
Madrid, Spain
United Kingdom
Barking, Havering and Redbridge Hospital Active, not recruiting
Romford, United Kingdom
Sponsors and Collaborators
Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
European Society of Intensive Care Medicine
University of Milan
University of Milano Bicocca
Investigators
Principal Investigator: Tommaso Mauri, MD Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
Principal Investigator: Laurent Brochard, MD St Michael Hospital, Toronto, Canada

Publications of Results:
Other Publications:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
ClinicalTrials.gov Identifier: NCT03201263     History of Changes
Other Study ID Numbers: Sigh study
First Posted: June 28, 2017    Key Record Dates
Last Update Posted: July 2, 2017
Last Verified: June 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Respiratory Distress Syndrome, Newborn
Respiratory Distress Syndrome, Adult
Respiratory Insufficiency
Acute Lung Injury
Lung Diseases
Respiratory Tract Diseases
Respiration Disorders
Infant, Premature, Diseases
Infant, Newborn, Diseases
Lung Injury