Individualized PEEP settings for patients with acute respiratory distress syndrome

Individualized Positive End-expiRatory Pressure Guided by End-Expiratory Lung Volume in Moderate-to-severe Acute resPiratory Distress Syndrome.The IPERPEEP Study

This study is testing if using personalized breathing support settings can help people with severe lung issues feel better and recover faster in the ICU.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 132 (estimated)
• Ages: 18 Years to 85 Years
• Sex: All
• Sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS (Academic / other)
• Drugs / interventions: chemotherapy
• Locations: 10 sites (Bari and 9 other locations)
• Trial ID: NCT04012073 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to determine whether individualized positive end-expiratory pressure (PEEP) settings, guided by end-expiratory lung volume (EELV), can improve clinical outcomes in patients suffering from moderate-to-severe acute respiratory distress syndrome (ARDS). Patients will undergo a standardized mechanical ventilation protocol, followed by a decremental PEEP trial to measure EELV and assess optimal PEEP settings. Participants will then be randomized to receive either individualized PEEP based on their EELV or a standard PEEP strategy. The primary endpoint will evaluate a composite clinical outcome including in-ICU mortality and ventilator-free days.

Who should consider this trial

Good fit: Ideal candidates are adults diagnosed with moderate-to-severe ARDS, specifically those with a PaO2/FiO2 ratio of 150 mmHg or lower.

Not a fit: Patients with conditions such as pneumothorax, acute brain injury, or severe heart failure may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could lead to improved survival rates and better recovery outcomes for patients with ARDS.

How similar studies have performed: Previous studies have indicated that individualized ventilation strategies can improve outcomes in ARDS, suggesting potential success for this novel approach.

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:

1. Acute respiratory failure within 1 week of a known clinical insult or new or worsening respiratory symptoms;
2. Bilateral infiltrates at the chest x-ray or CT scan, not fully explained by effusions, lobar/lung collapse, or nodules;
3. Respiratory failure not fully explained by cardiac failure or fluid overload; objective assessment required to exclude hydrostatic edema if no risk factor present.
4. PaO2/FiO2 ratio≤150 mmHg after 30 mins - 1 hour of mechanical ventilation with PEEP=5 cmH2O.
5. Written informed consent.

Exclusion Criteria:

1. Pregnancy;
2. Pneumothorax;
3. Acute brain injury;
4. 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;
5. Intubation as a result of an acute exacerbation of chronic pulmonary disease: chronic obstructive pulmonary disease, asthma, cystic fibrosis, etc;
6. Clinically evident intrinsic PEEP (≥2 cmH2O) during screening visit (End-expiratory pause to achieve Flow=0);
7. BMI\>35;
8. BMI\<15 or body weight\<35 Kg;
9. Any chronic disease requiring long-term oxygen therapy or mechanical ventilation at home;
10. Neuromuscular disease of any kind;
11. Severe chronic liver disease (Child-Pugh C or worse);
12. Bone marrow transplantation or chemotherapy-induced neutropenia;
13. History of liver or lung transplant;
14. Decision to withhold life-sustaining treatment;
15. Need for therapy with inhaled nitric oxide due to documented pulmonary arterial hypertension;
16. Life-threatening hypoxemia deemed to require extracorporeal membrane oxygenation (ECMO);
17. Presence of documented barotrauma;
18. 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).
19. 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).
20. More than 24 hours from endotracheal intubation to the time of the screening visit.

Where this trial is running

Bari and 9 other locations

• Policlinico di Bari — Bari, Italy (Not_yet_recruiting)
• Policlinico Sant'Orsola — Bologna, Italy (Not_yet_recruiting)
• Azienda ospedaliero-universitaria Mater Domini — Catanzaro, Italy (Not_yet_recruiting)
• SS. Annunziata hospital — Chieti, Italy (Not_yet_recruiting)
• Azienda ospedaliera universitaria di Ferrara-arcispedale Sant'Anna — Ferrara, Italy (Not_yet_recruiting)
• Ospedale San Martino — Genova, Italy (Not_yet_recruiting)
• Fondazione IRCCS Ca'Granda Ospedale Maggiore Policlinico — Milan, Italy (Not_yet_recruiting)
• Ospedale San Gerardo — Monza, Italy (Not_yet_recruiting)
• Fondazione IRCCS Policlinico San Matteo — Pavia, Italy (Not_yet_recruiting)
• Fondazione Policlinico Universitaro A. Gemelli IRCCS — Rome, Italy (Recruiting)

Study contacts

• Principal investigator: Domenico Luca Grieco, MD — Fondazione Policlinico Universitario A. Gemelli IRCCS; Università Cattolica del Sacro Cuore
• Study coordinator: Domenico Luca Grieco

Conditions Respiratory Distress Syndrome, Adult; Positive end-expiratory pressure; Ventilator-induced lung injury; Mechanical ventilation; Respiratory mechanics