[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-study-detail:100657330":3},{"organization":4,"outcomesModule":7,"designInfo":58,"detailedDescription":68,"studyPopulation":57,"armGroups":69,"interventions":82,"overallOfficials":89,"centralContacts":94,"locations":104,"responsibleParty":139,"collaborators":57,"id":142,"slug":143,"hasResults":144,"nctId":145,"briefTitle":146,"officialTitle":147,"acronym":148,"eligibilityCriteria":149,"healthyVolunteers":144,"sex":150,"minAge":151,"maxAge":57,"enrollmentInfo":152,"targetDuration":57,"studyType":155,"phases":156,"briefSummary":158,"conditions":159,"keywords":164,"overallStatus":128,"whyStopped":57,"lastUpdateSubmitDate":168,"lastUpdatePostDateStruct":169,"startDateStruct":172,"completionDateStruct":174,"leadSponsor":176,"locationsCount":177},{"fullName":5,"class":6},"Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)","OTHER",{"primaryOutcomes":8,"secondaryOutcomes":13,"otherOutcomes":57},[9],{"measure":10,"description":11,"timeFrame":12},"Number of days free from ventilation and alive at day 28 (VFD-28)","Ventilator-free days at day 28 (VFD-28) is defined as:\n\n* VFD-28 = 0 if a subject dies within 28 days of start of invasive ventilation;\n* VFD-28 = 0 if a subject is invasively ventilated for ≥28 days;\n* VFD-28 = 28 - X days after tracheal intubation if a subject is successfully liberated from ventilation.","From start of invasive ventilation to successful liberation from ventilation, death or day 28, whichever occurs first",[14,18,22,26,30,34,38,41,44,47,51,54],{"measure":15,"description":16,"timeFrame":17},"Duration of ventilation","Time difference between the date and time of the last successful liberation from invasive ventilation episode and the date and time of intubation.","From start of invasive ventilation to successful liberation from ventilation, death or day 28, whichever occurs first.",{"measure":19,"description":20,"timeFrame":21},"28-day mortality","Death for any cause within 28 days","from randomization to day 28",{"measure":23,"description":24,"timeFrame":25},"Intensive Care Unit (ICU) length of stay","Time difference between the date time of ICU discharge and the date and time of randomization","from randomization to ICU discharge, death or day 90, whichever occurs first.",{"measure":27,"description":28,"timeFrame":29},"Hospital length of stay","Time difference between the date time of hospital discharge and the date and time of randomization","from randomization to hospital discharge, death or day 90, whichever occurs first.",{"measure":31,"description":32,"timeFrame":33},"Successful switch to pressure support ventilation","ventilation in pressure support mode at two consecutive time points","from start of invasive ventilation to successful liberation from ventilation, death or day 28, whichever occurs first.",{"measure":35,"description":36,"timeFrame":37},"Intensive Care Unit (ICU) mortality","death from any cause in ICU","from randomization to day 90",{"measure":39,"description":40,"timeFrame":37},"Hospital mortality","death from any cause in hospital",{"measure":42,"description":43,"timeFrame":21},"Incidence of Acute Respiratory Distress Syndrome (ARDS)","ARDS is defined according to the Berlin definition.",{"measure":45,"description":46,"timeFrame":21},"Incidence of Acute Kidney Injury (AKI)","AKI is defined according to the KDIGO guidelines",{"measure":48,"description":49,"timeFrame":50},"Incidence of severe hypercapnia","Severe hypercapnia is defined as PaCO2 \\> 9.3 kPa (70 mmHg) with severe acidemia defined as pHa \\\u003C 7.20","from randomization to end of the intervention",{"measure":52,"description":53,"timeFrame":50},"Incidence of severe hypoxemia","Severe hypoxemia is defined as PaO2 \\\u003C 8 kPa (60 mmHg)",{"measure":55,"description":56,"timeFrame":50},"Incidence of ventilation-associated complications","Ventilator-associated complications are: (1) air leaks, (2) severe atelectasis, (3) ventilator-associated pneumonia, (4) acute cor pulmonale.",null,{"allocation":59,"interventionModel":60,"interventionModelDescription":61,"primaryPurpose":62,"observationalModel":57,"timePerspective":57,"maskingInfo":63},"RANDOMIZED","PARALLEL","International, multicenter, investigator-initiated, parallel, superiority randomized clinical trial","TREATMENT",{"masking":64,"maskingDescription":65,"whoMasked":66},"SINGLE","Outcome measures will be collected by an investigator blinded to the randomized treatment allocation. All analyses are preplanned, i.e., before closing of the database, and will be performed by an investigator that remains blinded for treatment allocation.",[67],"OUTCOMES_ASSESSOR","RATIONALE Injury caused by mechanical ventilation is associated with its intensity, of which the respiratory rate (RR) is a substantial contributor. A permissive ventilation strategy that reduces RR and allows mild hypercapnia, may lower the intensity of ventilation and improve patient-centered outcomes. In this approach, RR is stepwise decreased to the lowest level compatible with predefined safety limits.\n\nOBJECTIVE To compare permissive lung-protective ventilation with a lower RR, to conventional lung-protective ventilation, in adult critically ill patients receiving invasive ventilation.\n\nHYPOTHESIS Permissive lung-protective ventilation, defined as a strategy that reduces ventilatory intensity by stepwise lowering RR to the lowest level permitted by predefined safety limits, is superior to conventional lung-protective ventilation, with respect to the number of days free from ventilation and alive at day 28 (VFD-28) in adult critically ill patients receiving invasive ventilation.\n\nSTUDY DESIGN International, multicenter, investigator-initiated, randomized, clinical, superiority trial.\n\nSTUDY POPULATION Critically ill patients, aged ≥ 18 years, intubated and expected to receive invasive ventilation for \\> 24 hours.\n\nINTERVENTION AND COMPARISON Patients are randomized in a 1:1 ratio to permissive lung-protective ventilation with lower RR, or to conventional lung-protective ventilation.\n\nSTUDY ENDPOINTS The primary outcome is the number of VFD-28, a composite endpoint of duration of ventilation and death until day 28. The secondary outcomes include the individual components of this composite endpoint, namely duration of ventilation (analyzed separately in survivors and non-survivors) and 28-day mortality. Additional secondary outcomes are intensive care unit (ICU) and hospital length of stay, and ICU-, hospital, and 90-day mortality.\n\nSAMPLE SIZE AND DATA ANALYSIS Based on previous literature, we assumed that the intervention would determine an increase in the number of VFD-28 of 2.4 days, with a standard deviation of 10. The required sample size with a t-test and allowing for a 15% inflation to account for rank-based testing, a power of 90%, an alpha of 0.05 and a drop-out rate of 10% is 926 patients (463 patients per group). Primary analysis will follow the intention-to-treat principle, with additional per-protocol analysis.\n\nNATURE AND EXTENT OF THE BURDEN AND RISKS ASSOCIATED WITH PARTICIPATION, BENEFIT AND GROUP RELATEDNESS Ventilation with lower RR may result in higher PaCO2 and lower arterial pH. When kept within safe limits, evidence suggests that hypercapnia and mild acidosis are safe and do not lead to worse outcomes or severe adverse events. Both ventilation strategies are forms of lung-protective ventilation and are currently variably used as part of standard care. No other interventions are performed. Permissive ventilation is most often reserved for patients with severe lung conditions, where ventilator settings are more complex and ventilation intensity is high. In these patients, permissive ventilation is considered safe, and may even be beneficial. The collection of demographics, ventilation and outcome data causes no harm to patients. Blood is drawn for arterial blood gas analysis, but this is also part of standard care.",[70,76],{"label":71,"type":72,"description":73,"interventionNames":74},"Permissive lung-protective ventilation","EXPERIMENTAL","The goal is to achieve the lowest possible respiratory rate (RR) according to a guideline.",[75],"Other: Permissive lung-protective ventilation",{"label":77,"type":78,"description":79,"interventionNames":80},"Conventional lung-protective ventilation","ACTIVE_COMPARATOR","The respiratory rate is set according to standard of care.",[81],"Other: Conventional lung-protective ventilation",[83,86],{"type":6,"name":71,"description":84,"armGroupLabels":85,"otherNames":57},"The goal is to achieve the lowest possible respiratory rate (RR) guided by a nomogram, that integrates baseline RR with arterial blood gas analysis (ABG) results, to stay within safety limits of PaCO2 and pH. The lowest RR possible is determined by the maximum acceptable PaCO2 of ≤ 8.5 kPa (64 mmHg) and limited by the lowest acceptable pH of \\> 7.20, depending on the combination. The nomogram provides guidance on RR reductions based on these safety limits. The first target RR is determined using the baseline RR and the first ABG, obtained within 1 hour after randomization. The set RR is gradually decreased in steps of 2 breaths, approximately every 10 to 20 minutes, and downtitration is intended to be completed between 4 to 6 hours. Other ventilator settings are set according to lung-protective ventilation, following international guidelines.",[71],{"type":6,"name":77,"description":87,"armGroupLabels":88,"otherNames":57},"The respiratory rate (RR) is set according to standard of care, starting to target a normal PaCO2 (4.7-6.4 kPa or 35-48 mmHg) and\u002For a normal arterial pH (7.35-7.45). Other ventilator settings according to lung-protective ventilation, following international guidelines.",[77],[90],{"name":91,"affiliation":92,"role":93},"Frederique Paulus, Full Professor","Amsterdam AMC, Amsterdam, the Netherlands","PRINCIPAL_INVESTIGATOR",[95,100],{"name":96,"role":97,"phone":98,"phoneExt":57,"email":99},"Laura A. Buiteman-Kruizinga, PhD","CONTACT","+31627153843","l.a.kruizinga@amsterdamumc.nl",{"name":101,"role":97,"phone":102,"phoneExt":57,"email":103},"Amarens Hoogenboom, MD","+31615147102","h.b.a.hoogenboom@amsterdamumc.nl",[105,126],{"facility":106,"status":107,"city":108,"state":109,"zip":110,"country":111,"countryCode":109,"cosmosGeoPoint":112,"geoPoint":117,"contacts":118},"Amsterdam UMC, locatie AMC","NOT_YET_RECRUITING","Amsterdam","NL","1100 DD","Netherlands",{"type":113,"coordinates":114},"Point",[115,116],4.88969,52.37403,{"lat":116,"lon":115},[119,120,124],{"name":101,"role":97,"phone":102,"phoneExt":57,"email":103},{"name":121,"role":97,"phone":122,"phoneExt":57,"email":123},"Alessandro Caroli, MD","+393297869964","a.caroli@amsterdamumc.nl",{"name":101,"role":125,"phone":57,"phoneExt":57,"email":57},"SUB_INVESTIGATOR",{"facility":127,"status":128,"city":129,"state":109,"zip":130,"country":111,"countryCode":109,"cosmosGeoPoint":131,"geoPoint":135,"contacts":136},"Reinier De Graaf","RECRUITING","Delft","2625 AD",{"type":113,"coordinates":132},[133,134],4.35556,52.00667,{"lat":134,"lon":133},[137],{"name":138,"role":97,"phone":98,"phoneExt":57,"email":99},"Laura Buiteman-Kruizinga, PhD",{"type":93,"investigatorFullName":140,"investigatorTitle":141,"investigatorAffiliation":5,"oldNameTitle":57,"oldOrganization":57},"Laura Buiteman-Kruizinga","Principal Investigator","100657330","permissive-lung-protective-ventilation-rct-100657330",false,"NCT07837128","PERMISSive Lung-protective Ventilation RCT","PERMISSive Lung-protective Ventilation in Critically Ill Invasively Ventilated Patients (PERMISS) - a Randomized Clinical Trial","PERMISS","Inclusion Criteria:\n\n* admission to one of the participating intensive care units (ICUs);\n* intubated and receiving invasive ventilation; and\n* expected duration of ventilation of at least 24 hours (based on ICU admission diagnosis and clinical judgment).\n\nExclusion Criteria:\n\n* age below 18 years;\n* invasive ventilation before randomization \\> 2 hours in the ICU or invasive ventilation \\> 6 hours in the operating room or emergency department directly preceding the current ICU admission;\n* receiving or planned to receive veno-venous, veno-arterial or arterio-venous extracorporeal membrane oxygenation (ECMO);\n* contraindications for hypercapnia, such as ongoing cardiac ischemia (as defined in the guideline of the European Society of Cardiology), or having suspected or confirmed increased intracranial pressure due to (traumatic) brain injury, judged by the attending physician;\n* having severe Chronic Obstructive Pulmonary Disease (COPD); GOLD classification III or IV or classified in group B or E of the GOLD ABE assessment tool);\n* after cardiac arrest;\n* suspected or confirmed pregnancy;\n* having any neurologic diagnosis that can prolong duration of mechanical ventilation, e.g., Guillain-Barré syndrome, high spinal cord lesion or amyotrophic lateral sclerosis, multiple sclerosis, or myasthenia gravis;\n* participation in another interventional trial using similar endpoints;\n* previous randomization in this study;\n* no informed consent or;\n* admitted for palliative and terminal care.","ALL","18 Years",{"count":153,"type":154},926,"ESTIMATED","INTERVENTIONAL",[157],"NA","The goal of this clinical trial is to investigate the impact of a ventilation strategy with a lower respiratory rate (RR) (permissive lung-protective ventilation) on clinical outcomes in adult critically ill patients receiving invasive ventilation.\n\nThe main question it aims to answer is:\n\nIs a permissive lung-protective ventilation, defined as a strategy that reduces ventilatory intensity by stepwise lowering RR to the lowest level permitted by predefined safety limits, superior to conventional lung-protective ventilation, with respect to the number of days free from ventilation and alive at day 28 (VFD-28) in adult critically ill patients receiving invasive ventilation?\n\nResearchers will compare permissive lung-protective ventilation with conventional lung-protective ventilation to see if it improves clinical outcomes.\n\nParticipants will be randomly assigned to one of the two ventilation strategies under investigation and followed up for 28 days.",[160,161,162,163],"Invasive Ventilation","Critical Illness","Intensive Care (ICU)","Mechanical Ventilation",[165,163,166,167],"Intensive Care","respiratory rate","mechanical power","2026-09-22",{"date":170,"type":171},"2026-09-23","ACTUAL",{"date":173,"type":154},"2026-09",{"date":175,"type":154},"2029-09",{"name":5,"class":6},2]