Back to resultsIndividualized Positive End-expiratory Pressure Guided by End-expiratory Lung Volume in the Acute Respiratory Distress Syndrome (IPERPEEP)
Primary Purpose
Respiratory Distress Syndrome, Adult
Status
Recruiting
Phase
Phase 3
Locations
Italy
Study Type
Interventional
Intervention
Invasive Mechanical ventilation
Neuromuscular Blocking Agents
Prone positioning
Resume of spontaneous breathing
Rescue treatments
Weaning from PEEP
Weaning from mechanical ventilation
Extubation
Sponsored by
About this trial
This is an interventional treatment trial for Respiratory Distress Syndrome, Adult focused on measuring Positive end-expiratory pressure, Ventilator-induced lung injury, Mechanical ventilation, Respiratory mechanics
Eligibility Criteria
Eligibility inclusion criteria, according to the ARDS Berlin definition, will be assessed within the first 24 hours from the initiation of invasive mechanical ventilation:
- Acute respiratory failure within 1 week of a known clinical insult or new or worsening respiratory symptoms;
- Bilateral infiltrates at the chest x-ray or CT scan, not fully explained by effusions, lobar/lung collapse, or nodules;
- Respiratory failure not fully explained by cardiac failure or fluid overload; objective assessment required to exclude hydrostatic edema if no risk factor present.
- PaO2/FiO2 ratio≤150 mmHg after 30 mins - 1 hour of mechanical ventilation with PEEP=5 cmH2O.
- Written informed consent.
Exclusion Criteria:
- Pregnancy;
- Pneumothorax;
- Acute brain injury;
- Clinical signs of history of decompensated heart failure (New York Heart Association class 3-4 before the acute phase of the disease or documented ejection fraction<35% or pulmonary capillary wedge pressure>18 mmHg) or acute coronary syndrome;
- Intubation as a result of an acute exacerbation of chronic pulmonary disease: chronic obstructive pulmonary disease, asthma, cystic fibrosis, etc;
- Clinically evident intrinsic PEEP (≥2 cmH2O) during screening visit (End-expiratory pause to achieve Flow=0);
- BMI>35;
- BMI<15 or body weight<35 Kg;
- Any chronic disease requiring long-term oxygen therapy or mechanical ventilation at home;
- Neuromuscular disease of any kind;
- Severe chronic liver disease (Child-Pugh C or worse);
- Bone marrow transplantation or chemotherapy-induced neutropenia;
- History of liver or lung transplant;
- Decision to withhold life-sustaining treatment;
- Need for therapy with inhaled nitric oxide due to documented pulmonary arterial hypertension;
- Life-threatening hypoxemia deemed to require extracorporeal membrane oxygenation (ECMO);
- Presence of documented barotrauma;
- High risk of mortality within 3 months from other than ARDS (severe neurological damage, age >85 years and cancer patients in terminal stages of the disease).
- Persistent hemodynamic instability, intractable shock (norepinephrine>1 mcg/kg/h and/or blood lactate>5 mmol/L and/or considered too hemodynamically unstable for enrolment in the study by the patient's managing physician).
- More than 24 hours from endotracheal intubation to the time of the screening visit.
Sites / Locations
- Policlinico di Bari
- Policlinico Sant'Orsola
- Azienda ospedaliero-universitaria Mater Domini
- SS. Annunziata hospital
- Azienda ospedaliera universitaria di Ferrara-arcispedale Sant'Anna
- Ospedale San Martino
- Fondazione IRCCS Ca'Granda Ospedale Maggiore Policlinico
- Ospedale San Gerardo
- Fondazione IRCCS Policlinico San Matteo
- Fondazione Policlinico Universitaro A. Gemelli IRCCSRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
IPERPEEP
EXPRESS
Arm Description
End expiratory lung volume (EELV) will be measured at each step during a 5-step decremental PEEP trial. PEEP will be ≥5 cmH2O and set to ensure the maximum recruitment observed in the PEEP trial, with a maximum permitted PPLAT of 30 cmH2O. In particular, when interpreting the results of the PEEP trial, recruitment-to-inflation (RI) ratio calculated across two adjacent PEEP levels will drive PEEP setting. RI≥1.5 between two PEEP levels will lead to the setting of the higher PEEP. RI<0.5 will lead to the setting of the lower PEEP value. In case of RI≥0.5 and <1.5, the choice among two adjacent PEEP levels will be left to the attending physician, who will indicate the set PEEP in order to best balance between the commitment of limiting total, static and dynamic strain and of optimizing oxygenation and haemodynamics.
PEEP set so that the plateau pressure is within the following limits: 28 cmH2O≤Pplat≤ 30 cmH2O
Outcomes
Primary Outcome Measures
Composite clinical outcome that incorporates ICU mortality, 60-day ventilation-free days (VFD60) and the Area Under the Curve of the InterLeukin-6 serum concentration (IL6AUC) during the first 72 hours of observation
Composite clinical outcome that incorporates ICU mortality, 60-day ventilation-free days (VFD60) and the Area Under the Curve of the InterLeukin-6 serum blood cytokine concentration (IL6AUC) during the first 72 hours of observation. Every participant in the treatment group will be compared with every participant in the control group and assigned a score resulting from each comparison. Mortality takes precedence over VFD60, which takes precedence over IL6AUC. Two VFD60's will be considered different for the purpose of scoring only if their difference is larger than 5 days. Similarly, two IL6AUC's measurements will be considered different only if their difference exceeds 10% of the smaller of the two. These individual-comparison scores are added up to obtain the cumulative score primary endpoint for each participant. The sum of scores for patients in the treatment group is compared to the sum of scores of subjects in the control group and compared according by use of Mann-Whitney test
Secondary Outcome Measures
In-ICU mortality
Mortality at ICU discharge
In-Hospital mortality
Mortality at hospital discharge
90-day mortality
Mortality at 90 days from randomization
28-day Ventilator free days
The days spent without ventilator assistance within 28 days from randomization
60-day Ventilator free days
The days spent without ventilator assistance within 60 days from randomization
Time to successful weaning
The time from enrolment to successful liberation from mechanical ventilation
Time spent on assisted ventilation after the enrolment
The time spent on assisted ventilation on 28-day basis
AUC IL-6
Area under the curve (AUC) of serum interleukin 6 in the initial 72 hours of treatment
AUC IL-8
Area under the curve (AUC) of serum interleukin 8 in the initial 72 hours of treatment
AUC TNF
Area under the curve (AUC) of serum tumor necrosis factor in the initial 72 hours of treatment
Plateau pressure
Plateau pressure during the assigned treatment
Total Lung stress-End-inspiratory transpulmonary pressure derived from elastance ratio
Total increase in transpulmonary pressure due to tidal volume and PEEP during the assigned treatment
Static stress
Total increase in transpulmonary pressure due to PEEP during the assigned treatment
Set PEEP
Set PEEP during the assigned treatment
Set PEEP variability
Ratio of standard deviation to mean PEEP during the assigned treatment
End-expiratory transpulmonary pressure
Directly measured end-expiratory transpulmonary pressure during the assigned treatment
Dynamic stress-Transpulmonary driving pressure
Total increase in transpulmonary pressure due to tidal volume during the assigned treatment
Respiratory system driving pressure
The difference between Plateau Pressure and total PEEP during the assigned treatment
Respiratory system compliance
Ratio of tidal volume to respiratory system driving pressure during the assigned treatment
Respiratory system compliance normalized to predicted body weight
Ratio of respiratory system compliance and predicted body weight during the assigned treatment
Lung compliance
Ratio of tidal volume to transpulmonary driving pressure during the assigned treatment
Dynamic strain
Ratio of tidal volume to end-expiratory aerated volume (end-expiratory lung volume plus PEEP-induced alveolar recruitment) at study start
Static strain
Ratio of PEEP-induced overdistension volume to end-expiratory aerated volume (end-expiratory lung volume plus PEEP-induced alveolar recruitment) at study start
Oxygenation
Ratio of PaO2 to FiO2 during the assigned treatment
Oxygenation stretch index
Ratio of PaO2/FiO2 to respiratory system driving pressure during the assigned treatment
Carbon dioxide
Arterial pressure of CO2 during the assigned treatment
Heart rate
Heart rate during the assigned treatment
Arterial pressure
Mean arterial pressure during the assigned treatment
Simplified organ failure assessment
Simplified organ failure assessment (SOFA) after randomization
Catecholamine requirements per day
Catecholamin administration ad dosage during the assigned treatment
Organ failure
Organ failure free days on a 28-day basis, as defined by the simplified organ failure assessment (SOFA)
Need for rescue recruitment maneuvers
The proportion of patients needing rescue recruitment maneuvers during the assigned treatment
Nedd for rescue extra-corporeal membrane oxygenation
The proportion of patients needing rescue extra-corporeal membrane oxygenation due to persistent hypoxemia
Nedd for tracheostomy
The proportion of patients needing tracheostomy to enhance the weaning process
Full Information
NCT ID
NCT04012073
First Posted
July 4, 2019
Last Updated
December 5, 2022
Sponsor
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Collaborators
ClinicalTrialCenter, FerrarioDati, General Electric
1. Study Identification
Unique Protocol Identification Number
NCT04012073
Brief Title
Individualized Positive End-expiratory Pressure Guided by End-expiratory Lung Volume in the Acute Respiratory Distress Syndrome
Acronym
IPERPEEP
Official Title
Individualized Positive End-expiRatory Pressure Guided by End-Expiratory Lung Volume in Moderate-to-severe Acute resPiratory Distress Syndrome.The IPERPEEP Study
Study Type
Interventional
2. Study Status
Record Verification Date
November 2022
Overall Recruitment Status
Recruiting
Study Start Date
November 1, 2022 (Actual)
Primary Completion Date
December 31, 2024 (Anticipated)
Study Completion Date
April 30, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Collaborators
ClinicalTrialCenter, FerrarioDati, General Electric
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
Yes
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
During the acute respiratory distress syndrome (ARDS), patients' response to positive end-expiratory pressure (PEEP) is variable according to different degrees of lung recruitability. The search for a tool to individualize PEEP on the basis of patients' individual response is warranted.
Measurement of end-expiratory lung volume (EELV) by the nitrogen washin-washout technique, bedside available from recent ICU ventilators, has been shown to reliably estimate PEEP-induced alveolar recruitment and may therefore help titrate PEEP on patient's individual requirements.
The authors designed an open-label, multicenter, randomized trial to test whether an individualized PEEP setting protocol driven by EELV may improve a composite clinical outcome in patients with moderate-to-severe ARDS.
Detailed Description
ARDS patients with a PaO2/FiO2 ratio equal or below 150 mmHg (during mechanical ventilation with PEEP 5 cmH2O) will be enrolled within 24 hours from endo-tracheal intubation.
To standardize lung volumes at study initiation, all patients will undergo mechanical ventilation with tidal volume set at 6 ml/kg of predicted body weight and PEEP set to obtain a plateau pressure within 28 and 30 cmH2O for thirty minutes (Express PEEP).
Afterwards, a 5-step decremental PEEP trial will be conducted (Express PEEP to PEEP 5 cmH2O), and EELV will be measured at each step. PEEP-induced alveolar recruitment will be calculated for each PEEP range as the difference between PEEP-induced change EELV and the predicted increase in lung volume due to PEEP (PEEP-induced overdistension, equal to the product of respiratory system compliance and PEEP change).
Patients will be then randomized to receive mechanical ventilation with PEEP set according to the optimal recruitment observed in the PEEP trial (IPERPEEP arm) trial or according to the Express strategy (Control arm, PEEP set to achieve a plateau pressure of 28-30 cmH2O).
In both groups, tidal volume size, the use of prone positioning and neuromuscular blocking agents will be standardized.
Primary endpoint of the study is a composite clinical outcome incorporating in-ICU mortality, 60-day ventilator free days and the area under the curve of serum Interleukin 6 over the course of the initial 72 hours.
Primary and secondary endpoints will also be analyzed in subgroups, as defined below:
∆EELV5-16/FRC ≥ 73% [18] during the PEEP trial
∆EELV5-16/FRC < 73%[23] during the PEEP trial
Recruitment-to-inflation ratio (RI) ≥ 1 and <1 across the range between the lowest and highest PEEP tested during the PEEP trial
P/F ratio<100 mmHg at study inclusion
IL-6>400 pg/ml at study inclusion
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Respiratory Distress Syndrome, Adult
Keywords
Positive end-expiratory pressure, Ventilator-induced lung injury, Mechanical ventilation, Respiratory mechanics
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
Randomization will be stratified according to Recruitment/cmH2O ≥ or < 19 ml/cmH2O across the range between the lowest and highest PEEP tested during the initial PEEP trial
Masking
None (Open Label)
Allocation
Randomized
Enrollment
132 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
IPERPEEP
Arm Type
Experimental
Arm Description
End expiratory lung volume (EELV) will be measured at each step during a 5-step decremental PEEP trial.
PEEP will be ≥5 cmH2O and set to ensure the maximum recruitment observed in the PEEP trial, with a maximum permitted PPLAT of 30 cmH2O.
In particular, when interpreting the results of the PEEP trial, recruitment-to-inflation (RI) ratio calculated across two adjacent PEEP levels will drive PEEP setting.
RI≥1.5 between two PEEP levels will lead to the setting of the higher PEEP.
RI<0.5 will lead to the setting of the lower PEEP value.
In case of RI≥0.5 and <1.5, the choice among two adjacent PEEP levels will be left to the attending physician, who will indicate the set PEEP in order to best balance between the commitment of limiting total, static and dynamic strain and of optimizing oxygenation and haemodynamics.
Arm Title
EXPRESS
Arm Type
Active Comparator
Arm Description
PEEP set so that the plateau pressure is within the following limits: 28 cmH2O≤Pplat≤ 30 cmH2O
Intervention Type
Device
Intervention Name(s)
Invasive Mechanical ventilation
Intervention Description
Volume-control ventilation with tidal volume will be set at 6 mL/Kg of predicted body weight, respiratory rate to maintain pH>7.30 and PaCO2<50 mmHg and FiO2 will be set to achieve a SpO2>88-95%.
In case of hypercapnia with Ph<7.30 despite a respiratory rate=30-35, an increase in tidal volume up to 8 ml/kg will be allowed.
In both groups, the assigned ventilation protocol will be followed for a minimum of 72 hours from randomization and any time fully controlled ventilation is deemed necessary by the attending physician up to 14 days from randomization. After 14 days from randomization, PEEP will be set according to the clinical practice of each institution.
After 72 hours from the study protocol, the PEEP setting protocol according to the assigned treatment will be resumed at any time within 14 days from enrolment if fully controlled ventilation is established, according to the decision of the attending physician in charge.
Intervention Type
Drug
Intervention Name(s)
Neuromuscular Blocking Agents
Intervention Description
All patients will receive NMBA for 48 hours after the enrolment. The decision to stop NMBA administration after 48 hours will be left to the attending physician, but muscle paralysis will be strongly encouraged if PaO2/FiO2 ratio remains lower than 80-100 mmHg. NMBA administration will be resumed anytime deemed necessary by the attending physician.
Intervention Type
Procedure
Intervention Name(s)
Prone positioning
Intervention Description
Prone positioning will be used in all enrolled patients as a standard of care: the decision about the timing and the duration of prone position sessions will be left to the attending physician and the time spent by the patient in the prone and in the supine position will be recorded: PEEP will be re-set according to the protocol of the allocated treatment anytime patient's position is changed.
Intervention Type
Procedure
Intervention Name(s)
Resume of spontaneous breathing
Intervention Description
Assist/control and assist ventilation will be allowed after 72 hours from the enrolment if deemed appropriate by the attending physician.
During spontaneous breathing, PEEP will be set according to the decision of the attending physician and the practice of each institution: however, in order to standardize the treatments, moderate PEEP (10-15 cmH2O) will be encouraged in case of moderate hypoxemia (PaO2/FiO2<150 mmHg) in control group, while PEEP close to the value set during controlled ventilation according to the treatment protocol but <15 cmH2O will be suggested in the intervention group.
During assist/control and assisted ventilation, PEEP will never be higher than the last PEEP set according to the assigned protocol during controlled ventilation.
Fully controlled mechanical ventilation will be resumed any time during the study period if the patient meets the criteria described above or any time deemed necessary by the physicians in charge
Intervention Type
Procedure
Intervention Name(s)
Rescue treatments
Intervention Description
Recruitment maneuvers, extracorporeal membrane oxygenation (ECMO), extracorporeal CO2 removal (ECCO2-R) after randomization will be allowed in both groups as rescue therapies and according to the decision of attending physicians: any of these procedures will be accurately recorded on the case report form.
Intervention Type
Procedure
Intervention Name(s)
Weaning from PEEP
Intervention Description
In order not to delay weaning from mechanical ventilation, when a patient is managed with assist/control or assist ventilation with PEEP higher than 8 cmH2O, a daily PEEP weaning trial will be performed whether PaO2/FIO2 ratio>150 mm Hg and FIO2<0.5: PEEP will be decreased to 8-5 cm H2O and arterial blood gas will be sampled after 20 -0 minutes. Previous ventilatory settings will be resumed if during the procedure transcutaneous oxyhemoglobin saturation decreases below 88%, PaO2/FIO2 falls below 150 mm Hg or if the patient experiences abnormal changes in respiratory rate or other clinical signs suggestive of respiratory distress.
When PaO2/FIO2 is no lower than 200 mm Hg at PEEP≤8 cmH2O, the patient will be considered to have acceptable gas exchange on 8-5 cmH2O of PEEP and will be deemed capable to tolerate this setting
Intervention Type
Procedure
Intervention Name(s)
Weaning from mechanical ventilation
Intervention Description
A 30-120-minute spontaneous breathing trial will be initiated as the following criteria are met and whether the patient tolerates fully assist ventilation with PEEP≤8 cmH2O for at least 4 hours without experiencing hypoxemia (SpO2<88% or PaO2/FiO2<150mmHg):
improvement or resolution of the underlying cause of acute respiratory failure
normal sensorium
correction of arterial hypoxemia (PaO2 ≥ 60 mmHg at a FiO2 ≤ 0.4 with PEEP ≤ 8 cmH2O);
absence of fever (≥ 38 °C) or sepsis;
blood hemoglobin concentration of 7 g/dL or more;
hemodynamic stability
For the purpose of the study, success of the spontaneous breathing trial will be defined as presence of the following criteria:
respiratory rate < 35/min,
arterial oxygen saturation ≥ 90%,
heart rate < 120/min,
systolic blood pressure > 90 and < 160 mmHg
adequate cough. If the spontaneous breathing trial is successful, the patient will be extubated.
Intervention Type
Procedure
Intervention Name(s)
Extubation
Intervention Description
Each extubated patient will undergo oxygen therapy via high flow nasal cannula (maximum flows tolerated and FiO2 titrated to obtain 96%>SpO2>92%). Pre-emptive noninvasive ventilation (NIV) after extubation will be allowed in prolonged to wean patients (i.e. more than 3 SBT failure or more than 7 days from the first spontaneous breathing trial to being extubated) if deemed necessary by the physician in charge.
In case of respiratory failure during oxygen therapy via high flow nasal cannula after extubation and, a rescue NIV trial will be allowed before intubation in both groups at the discretion of the attending physician.
Primary Outcome Measure Information:
Title
Composite clinical outcome that incorporates ICU mortality, 60-day ventilation-free days (VFD60) and the Area Under the Curve of the InterLeukin-6 serum concentration (IL6AUC) during the first 72 hours of observation
Description
Composite clinical outcome that incorporates ICU mortality, 60-day ventilation-free days (VFD60) and the Area Under the Curve of the InterLeukin-6 serum blood cytokine concentration (IL6AUC) during the first 72 hours of observation. Every participant in the treatment group will be compared with every participant in the control group and assigned a score resulting from each comparison. Mortality takes precedence over VFD60, which takes precedence over IL6AUC. Two VFD60's will be considered different for the purpose of scoring only if their difference is larger than 5 days. Similarly, two IL6AUC's measurements will be considered different only if their difference exceeds 10% of the smaller of the two. These individual-comparison scores are added up to obtain the cumulative score primary endpoint for each participant. The sum of scores for patients in the treatment group is compared to the sum of scores of subjects in the control group and compared according by use of Mann-Whitney test
Time Frame
60 days
Secondary Outcome Measure Information:
Title
In-ICU mortality
Description
Mortality at ICU discharge
Time Frame
90 days
Title
In-Hospital mortality
Description
Mortality at hospital discharge
Time Frame
90 days
Title
90-day mortality
Description
Mortality at 90 days from randomization
Time Frame
90 days
Title
28-day Ventilator free days
Description
The days spent without ventilator assistance within 28 days from randomization
Time Frame
28 days
Title
60-day Ventilator free days
Description
The days spent without ventilator assistance within 60 days from randomization
Time Frame
28 days
Title
Time to successful weaning
Description
The time from enrolment to successful liberation from mechanical ventilation
Time Frame
90 days
Title
Time spent on assisted ventilation after the enrolment
Description
The time spent on assisted ventilation on 28-day basis
Time Frame
28 days
Title
AUC IL-6
Description
Area under the curve (AUC) of serum interleukin 6 in the initial 72 hours of treatment
Time Frame
72 hours
Title
AUC IL-8
Description
Area under the curve (AUC) of serum interleukin 8 in the initial 72 hours of treatment
Time Frame
72 hours
Title
AUC TNF
Description
Area under the curve (AUC) of serum tumor necrosis factor in the initial 72 hours of treatment
Time Frame
72 hours
Title
Plateau pressure
Description
Plateau pressure during the assigned treatment
Time Frame
72 hours
Title
Total Lung stress-End-inspiratory transpulmonary pressure derived from elastance ratio
Description
Total increase in transpulmonary pressure due to tidal volume and PEEP during the assigned treatment
Time Frame
72 hours
Title
Static stress
Description
Total increase in transpulmonary pressure due to PEEP during the assigned treatment
Time Frame
72 hours
Title
Set PEEP
Description
Set PEEP during the assigned treatment
Time Frame
72 hours
Title
Set PEEP variability
Description
Ratio of standard deviation to mean PEEP during the assigned treatment
Time Frame
72 hours
Title
End-expiratory transpulmonary pressure
Description
Directly measured end-expiratory transpulmonary pressure during the assigned treatment
Time Frame
72 hours
Title
Dynamic stress-Transpulmonary driving pressure
Description
Total increase in transpulmonary pressure due to tidal volume during the assigned treatment
Time Frame
72 hours
Title
Respiratory system driving pressure
Description
The difference between Plateau Pressure and total PEEP during the assigned treatment
Time Frame
72 hours
Title
Respiratory system compliance
Description
Ratio of tidal volume to respiratory system driving pressure during the assigned treatment
Time Frame
72 hours
Title
Respiratory system compliance normalized to predicted body weight
Description
Ratio of respiratory system compliance and predicted body weight during the assigned treatment
Time Frame
72 hours
Title
Lung compliance
Description
Ratio of tidal volume to transpulmonary driving pressure during the assigned treatment
Time Frame
72 hours
Title
Dynamic strain
Description
Ratio of tidal volume to end-expiratory aerated volume (end-expiratory lung volume plus PEEP-induced alveolar recruitment) at study start
Time Frame
30 minutes
Title
Static strain
Description
Ratio of PEEP-induced overdistension volume to end-expiratory aerated volume (end-expiratory lung volume plus PEEP-induced alveolar recruitment) at study start
Time Frame
30 minutes
Title
Oxygenation
Description
Ratio of PaO2 to FiO2 during the assigned treatment
Time Frame
72 hours
Title
Oxygenation stretch index
Description
Ratio of PaO2/FiO2 to respiratory system driving pressure during the assigned treatment
Time Frame
72 hours
Title
Carbon dioxide
Description
Arterial pressure of CO2 during the assigned treatment
Time Frame
72 hours
Title
Heart rate
Description
Heart rate during the assigned treatment
Time Frame
72 hours
Title
Arterial pressure
Description
Mean arterial pressure during the assigned treatment
Time Frame
72 hours
Title
Simplified organ failure assessment
Description
Simplified organ failure assessment (SOFA) after randomization
Time Frame
28 days
Title
Catecholamine requirements per day
Description
Catecholamin administration ad dosage during the assigned treatment
Time Frame
72 hours
Title
Organ failure
Description
Organ failure free days on a 28-day basis, as defined by the simplified organ failure assessment (SOFA)
Time Frame
28 days
Title
Need for rescue recruitment maneuvers
Description
The proportion of patients needing rescue recruitment maneuvers during the assigned treatment
Time Frame
72 hours
Title
Nedd for rescue extra-corporeal membrane oxygenation
Description
The proportion of patients needing rescue extra-corporeal membrane oxygenation due to persistent hypoxemia
Time Frame
90 days
Title
Nedd for tracheostomy
Description
The proportion of patients needing tracheostomy to enhance the weaning process
Time Frame
90 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Eligibility inclusion criteria, according to the ARDS Berlin definition, will be assessed within the first 24 hours from the initiation of invasive mechanical ventilation:
Acute respiratory failure within 1 week of a known clinical insult or new or worsening respiratory symptoms;
Bilateral infiltrates at the chest x-ray or CT scan, not fully explained by effusions, lobar/lung collapse, or nodules;
Respiratory failure not fully explained by cardiac failure or fluid overload; objective assessment required to exclude hydrostatic edema if no risk factor present.
PaO2/FiO2 ratio≤150 mmHg after 30 mins - 1 hour of mechanical ventilation with PEEP=5 cmH2O.
Written informed consent.
Exclusion Criteria:
Pregnancy;
Pneumothorax;
Acute brain injury;
Clinical signs of history of decompensated heart failure (New York Heart Association class 3-4 before the acute phase of the disease or documented ejection fraction<35% or pulmonary capillary wedge pressure>18 mmHg) or acute coronary syndrome;
Intubation as a result of an acute exacerbation of chronic pulmonary disease: chronic obstructive pulmonary disease, asthma, cystic fibrosis, etc;
Clinically evident intrinsic PEEP (≥2 cmH2O) during screening visit (End-expiratory pause to achieve Flow=0);
BMI>35;
BMI<15 or body weight<35 Kg;
Any chronic disease requiring long-term oxygen therapy or mechanical ventilation at home;
Neuromuscular disease of any kind;
Severe chronic liver disease (Child-Pugh C or worse);
Bone marrow transplantation or chemotherapy-induced neutropenia;
History of liver or lung transplant;
Decision to withhold life-sustaining treatment;
Need for therapy with inhaled nitric oxide due to documented pulmonary arterial hypertension;
Life-threatening hypoxemia deemed to require extracorporeal membrane oxygenation (ECMO);
Presence of documented barotrauma;
High risk of mortality within 3 months from other than ARDS (severe neurological damage, age >85 years and cancer patients in terminal stages of the disease).
Persistent hemodynamic instability, intractable shock (norepinephrine>1 mcg/kg/h and/or blood lactate>5 mmol/L and/or considered too hemodynamically unstable for enrolment in the study by the patient's managing physician).
More than 24 hours from endotracheal intubation to the time of the screening visit.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Domenico Luca Grieco
Phone
+39 06 3015
Ext
4490
Email
dlgrieco@outlook.it
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Massimo Antonelli, MD
Organizational Affiliation
Fondazione Policlinico Universitario A. Gemelli IRCCS; Università Cattolica del Sacro Cuore
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Domenico Luca Grieco, MD
Organizational Affiliation
Fondazione Policlinico Universitario A. Gemelli IRCCS; Università Cattolica del Sacro Cuore
Official's Role
Principal Investigator
Facility Information:
Facility Name
Policlinico di Bari
City
Bari
Country
Italy
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Rosa Di Mussi, MD
First Name & Middle Initial & Last Name & Degree
Salvatore Grasso, MD
Facility Name
Policlinico Sant'Orsola
City
Bologna
Country
Italy
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Elisabetta Pierucci, MD
First Name & Middle Initial & Last Name & Degree
Elisabetta Pierucci, MD
First Name & Middle Initial & Last Name & Degree
Vito Marco Ranieri, MD
First Name & Middle Initial & Last Name & Degree
Antonio Siniscalchi, MD
Facility Name
Azienda ospedaliero-universitaria Mater Domini
City
Catanzaro
Country
Italy
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Paolo Navalesi, MD
First Name & Middle Initial & Last Name & Degree
Paolo Navalesi, MD
First Name & Middle Initial & Last Name & Degree
Federico Longhini, MD
First Name & Middle Initial & Last Name & Degree
Andrea Bruni, MD
First Name & Middle Initial & Last Name & Degree
Eugenio Garofalo, MD
Facility Name
SS. Annunziata hospital
City
Chieti
Country
Italy
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Salvatore M Maggiore, MD, PhD
First Name & Middle Initial & Last Name & Degree
Salvatore M Maggiore, MD, PhD
Facility Name
Azienda ospedaliera universitaria di Ferrara-arcispedale Sant'Anna
City
Ferrara
Country
Italy
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Savino Spadaro, MD
First Name & Middle Initial & Last Name & Degree
Carlo Alberto Volta, MD
First Name & Middle Initial & Last Name & Degree
Savino Spadaro, MD
Facility Name
Ospedale San Martino
City
Genova
Country
Italy
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lorenzo Ball, MD
First Name & Middle Initial & Last Name & Degree
Paolo Pelosi, MD
First Name & Middle Initial & Last Name & Degree
Nicolò Patroniti, MD
First Name & Middle Initial & Last Name & Degree
Lorenzo Ball, MD
Facility Name
Fondazione IRCCS Ca'Granda Ospedale Maggiore Policlinico
City
Milan
Country
Italy
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Giacomo Grasselli, MD
First Name & Middle Initial & Last Name & Degree
Giacomo Grasselli, MD
First Name & Middle Initial & Last Name & Degree
Tommaso Mauri, MD
Facility Name
Ospedale San Gerardo
City
Monza
Country
Italy
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Giuseppe Foti, MD
First Name & Middle Initial & Last Name & Degree
Giuseppe Foti, MD
First Name & Middle Initial & Last Name & Degree
Giacomo Bellani, MD
First Name & Middle Initial & Last Name & Degree
Vincenzo Russotto, MD
Facility Name
Fondazione IRCCS Policlinico San Matteo
City
Pavia
Country
Italy
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Francesco Mojoli, MD
First Name & Middle Initial & Last Name & Degree
Francesco Mojoli, MD
First Name & Middle Initial & Last Name & Degree
Giorgio Iotti, MD
First Name & Middle Initial & Last Name & Degree
Guido Tavazzi, MD
Facility Name
Fondazione Policlinico Universitaro A. Gemelli IRCCS
City
Rome
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Domenico Luca Grieco, MD
First Name & Middle Initial & Last Name & Degree
Massimo Antonelli, MD
First Name & Middle Initial & Last Name & Degree
Antonio M Dell'Anna, MD
First Name & Middle Initial & Last Name & Degree
Filippo Bongiovanni, MD
First Name & Middle Initial & Last Name & Degree
Giuseppe Bello, MD
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Individual patient data will be made available upon a reasonable request
Citations:
PubMed Identifier
35057852
Citation
Grieco DL, Maggiore SM, Bellani G, Spadaro S, Spinelli E, Tonetti T, Menga LS, Pozzi M, Battaglini D, Di Mussi R, Bruni A, De Gaetano A, Iovino CG, Brioni M, Mojoli F, Foti G, Volta CA, Pelosi P, Navalesi P, Grasso S, Ranieri VM, Antonelli M; IPERPEEP study group. Individualized positive end-expiratory pressure guided by end-expiratory lung volume in early acute respiratory distress syndrome: study protocol for the multicenter, randomized IPERPEEP trial. Trials. 2022 Jan 20;23(1):63. doi: 10.1186/s13063-021-05993-0.
Results Reference
derived
PubMed Identifier
33784416
Citation
Santa Cruz R, Villarejo F, Irrazabal C, Ciapponi A. High versus low positive end-expiratory pressure (PEEP) levels for mechanically ventilated adult patients with acute lung injury and acute respiratory distress syndrome. Cochrane Database Syst Rev. 2021 Mar 30;3(3):CD009098. doi: 10.1002/14651858.CD009098.pub3.
Results Reference
derived
Learn more about this trial
Individualized Positive End-expiratory Pressure Guided by End-expiratory Lung Volume in the Acute Respiratory Distress Syndrome
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