Mechanical VentilationPERMISS pilotNCT07077174
Effects of PERMISSive Lung-protective Ventilation on Outcome in Critically Ill Invasively Ventilated Patients
A study testing Permissive lung-protective ventilation and Conventional lung-protective ventilation in people with Mechanical Ventilation and Intensive Care (ICU), run by Reinier de Graaf Groep at 5 sites in 2 countries.
Trial summary
RATIONALE Lung-protective ventilation using a lower respiratory rate (RR) is an appealing strategy to reduce ventilation intensity, which may require permissive hypercapnia. However, the feasibility and safety of this so-called 'permissive lung-protective ventilation' must be investigated, before conducting a large… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Mechanical Ventilation, Intensive Care (ICU)
- What is being tested?
- Permissive lung-protective ventilation and Conventional lung-protective ventilation
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 56 participants
- Where
- 5 sitesin 2 countries
- Study dates
- 31 Aug 2025to 31 Aug 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- admission to one of the participating ICUs;
- intubated and receiving invasive ventilation with an expected duration of ventilation of at least 24 hours.
Who cannot join
- age below 18 years;
- receiving invasive ventilation > 1 hour in the ICU, or receiving invasive ventilation > 6 hours directly preceding the current ICU admission (i.e., in the operating room or in the emergency department);
- receiving or planned to receive veno-venous, veno-arterial or arterio-venous extracorporeal membrane oxygenation (ECMO);
- having COPD GOLD III and IV;
- contra-indication 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 brain injury, judged by the attending physician;
- 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;
Show all 11Show fewer
- suspected or confirmed pregnancy;
- participation in another interventional trial using similar endpoints;
- previously randomized in this study;
- no informed consent; or
- admitted for terminal care
Trial locations and contacts
5 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
5 sites in 2 countries
Netherlands4 sites, 4 recruiting
- Recruiting
ZiekenhuisGroep Twente
Almelo
Ellen Platenkamp, RN, +3188 708 35 92, researchic@zgt.nl
- Recruiting
Amsterdam UMC
Amsterdam
David M.P. van Meenen, MD, PhD, d.m.p.vanmeenen@amsterdamumc.nl
- Recruiting
Reinier de Graaf Hospital
Delft
Laura A. Buiteman-Kruizinga, RN, PhD, +152604040, l.kruizinga@rdgg.nl
- Recruiting
Dijklander Hospital
Hoorn
Stephanie S. List, RN, +31229 - 257 799, s.s.list@dijklander.nl
Spain1 site, 1 recruiting
- Recruiting
Vall d'Hebron
Barcelona
Luis Morales, MD, PhD, +34 934 89 30 00, luchomq2077@gmail.com
About this study
Official title: Effects of PERMISSive Lung-protective Ventilation on Outcome in Critically Ill Invasively Ventilated Patients (PERMISS) - a Feasibility and Safety Pilot Study for a Randomized Clinical Trial
RATIONALE Lung-protective ventilation using a lower respiratory rate (RR) is an appealing strategy to reduce ventilation intensity, which may require permissive hypercapnia. However, the feasibility and safety of this so-called 'permissive lung-protective ventilation' must be investigated, before conducting a large randomized clinical trial to evaluate its effectiveness on patient-centered outcomes.
OBJECTIVE To study the feasibility and safety of permissive lung-protective ventilation in adult critically ill patients receiving invasive ventilation for acute hypoxemic respiratory failure, and to inform the design of a future randomized clinical trial in this patient population.
Read more
HYPOTHESIS Permissive lung-protective ventilation is a feasible and safe ventilation strategy.
STUDY DESIGN Multicenter, randomized clinical pilot trial. STUDY POPULATION Critically ill patients, aged > 18 years, intubated for acute hypoxemic respiratory failure, and expected to receive ventilation for > 24 hours.
METHODS Patients are randomized to permissive lung-protective ventilation wherein RR is stepwise reduced, or to conventional lung-protective ventilation.
OUTCOME MEASURES The primary endpoint is feasibility, assessed by the difference in respiratory rate (RR) between the two groups, from the start of mechanical ventilation until first extubation. Secondary endpoints include protocol compliance and feasibility of collecting data, and safety, assessed by the occurrence of unacceptable hypercapnia and hypoxemia and the incidence of ventilator-associated complications SAMPLE SIZE To estimate the appropriate sample size for this pilot study, we considered the primary feasibility endpoint of detecting a difference in the respiratory rate (RR). Assuming an expected mean difference in RR of 7.5, based on previous studies [1, 2], with an SD of 10, a power of 90% and an alpha of 0.05, with a drop-out rate estimated at 10%, a two-tailed t-test was used. The required sample size is 84 patients (42 patients per group).
NATURE AND EXTENT OF THE BURDEN AND RISKS ASSOCIATED WITH PARTICIPATION, BENEFIT AND GROUP RELATEDNESS Ventilation with a lower RR may require permissive hypercapnia, which, when kept within safe limits, is safe. In current daily practice, there is no guidance in setting RR; consequently, RR varies widely across patients and is often set high. This pilot study compares two forms of lung-protective ventilation, both considered standard care in current ICU practice. The control group receives conventional ventilation with low tidal volumes and high RR to maintain normal PaCO₂ and pH. The intervention group, permissive ventilation, uses a lower RR to reduce mechanical power, accepting mild hypercapnia and acidosis. 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. We aim to evaluate this strategy more broadly in critically ill patients. The collection of demographic, 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.
- Conditions
- Mechanical Ventilation, Intensive Care (ICU)
- Being tested
- Permissive lung-protective ventilation, Conventional lung-protective ventilation
- Keywords
- mechanical ventilation, intensive care unit, mechanical power, respiratory rate
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Permissive lung-protective ventilationOther
The goal is to achieve the lowest possible respiratory rate (RR) according to a guideline in which the target RR is estimated by combining the baseline RR with the results of arterial blood gas analysis (ABG), determined by the highest acceptable partial pressure of carbon dioxide (PaCO2) of ≤ 8.5 kPa (64 mmHg) but limited by the lowest acceptable arterial pH (pHa) of > 7.20. The RR is gradually decreased, in steps of 2 breaths every 10 minutes, based on continuous end-tidal CO2 monitoring. To ensure that the pHa does not fall below 7.20, following randomization, ABGs are repeated every hour until the target RR is reached, for at least 6 hours. Thereafter, blood gas analyses are repeated at least every 8 hours (at the start of every nursing shift). Down-titration of RR stops at a rate of 4 breaths per minute. This approach continues until the switch to spontaneous breathing. Of note, when the pHa is > 7.50, this must first be decreased to ≤ 7.50 based on local protocol.
Conventional lung-protective ventilationOther
Following randomization, which should happen within 1 hour after start of ventilation in the ICU, the RR is set according to standard of care, based on continuous end-tidal CO2 monitoring, to target a normal PaCO2 (4.7-6.4 kPa or 35-48 mmHg) combined with a pHa within the range of 7.35 to 7.45. Following randomization, blood gas analyses are repeated every hour for at least 6 hours, and thereafter at least every 8 hours (at the start of every nursing shift). This approach continues until the weaning phase.
| Study group | Role | What they receive |
|---|---|---|
| Permissive lung-protective ventilation | Experimental | The goal is to achieve the lowest possible respiratory rate (RR) according to a guideline < 1 hour after start of ventilation in the ICU. Receives: Other: Permissive lung-protective ventilation |
| Conventional lung-protective ventilation | Active comparator | The respiratory rate is set according to standard of care < 1 hour after start of ventilation in the ICU. Receives: Other: Conventional lung-protective ventilation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Feasibility of the intervention
Assessed by the difference in respiratory rate (RR) between the two groups
Measured: from the start of mechanical ventilation until first extubation, up to 28 days
Secondary outcomes (4)
Safety of the intervention
Assessed by the occurrence of unacceptable hypercapnia and hypoxemia and the incidence of ventilator-associated complications
Measured: From the start of mechanical ventilation until first extubation, up to 28 days.
Compliance of the protocol
Determined by reflecting whether the target RR was reached and maintained during the ventilation period in the permissive lung-protective ventilation group.
Measured: From the start of mechanical ventilation until first extubation, up to 28 days.
Compliance of the protocol
Determined by how often a patient was switched back to the other ventilation group
Measured: from start of ventilation until first extubation, up to 28 days.
Feasibility of collecting data
assessed by the amount of missing data
Measured: from start of mechanical ventilation until follow-up at day 90.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jul 2025
- Study start31 Aug 2025
- Primary completion31 Jul 2026 (estimated)
- Study completion31 Aug 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Mechanical VentilationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 56 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Reinier de Graaf Groep
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Laura Buiteman-Kruizinga, RN, PhD, Principal investigator, Reinier de Graaf GroepMarcus J. Schultz, MD, PhD, Study chair, Amsterdam UMC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07077174
- Sponsor's protocol ID
- NL-009624.P25.028
- Other IDs
- NL-OMON57603
- Acronym
- PERMISS pilot
- Status last verified
- Jul 2026
- First submitted
- 1 Jul 2025
- Last updated
- 8 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes
Publications
Caroli A, Hoogenboom A, Bugedo G, Damiani FL, Ferreira J, Abreu MG, Geerts JW, Grady BP, List SS, van Meenen DMP, Morales-Quinteros L, Paulus F, Serpa Neto A, Schultz MJ, Slutsky AS, Sodhi K, Urlings-Strop L, Buiteman-Kruizinga LA; PERMISS collaborative group; PROVE network. Effects of PERMISSive lung-protective ventilation on outcome in critically ill, invasively ventilated patients (PERMISS): protocol for a feasibility and safety randomised clinical trial. BMJ Open Respir Res. 2026 Sep 17;13(1):e004532. doi: 10.1136/bmjresp-2026-004532.
PubMed 42754304
Study at a glance
From the registry record, last updated by the sponsor on 8 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of PERMISSive Lung-protective Ventilation on Outcome in Critically Ill Invasively Ventilated Patients (PERMISS) - a Feasibility and Safety Pilot Study for a Randomized Clinical Trial
- ClinicalTrials.gov ID
- NCT07077174
- Acronym / sponsor ID
- PERMISS pilot / NL-009624.P25.028
- Conditions
- Mechanical Ventilation, Intensive Care (ICU)
- Keywords
- mechanical ventilation, intensive care unit, mechanical power, respiratory rate
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 56 participants (estimated)
- Lead sponsor
- Reinier de Graaf GroepUniversity, hospital or other
- Study start
- 31 Aug 2025 (actual)
- Primary completion
- 31 Jul 2026 (estimated)
- Study completion
- 31 Aug 2026 (estimated)
- First posted
- 22 Jul 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE Lung-protective ventilation using a lower respiratory rate (RR) is an appealing strategy to reduce ventilation intensity, which may require permissive hypercapnia. However, the feasibility and safety of this so-called 'permissive lung-protective ventilation' must be investigated, before conducting a large randomized clinical trial to evaluate its effectiveness on patient-centered outcomes.
OBJECTIVE To study the feasibility and safety of permissive lung-protective ventilation in adult critically ill patients receiving invasive ventilation for acute hypoxemic respiratory failure, and to inform the design of a future randomized clinical trial in this patient population.
HYPOTHESIS Permissive lung-protective ventilation is a feasible and safe ventilation strategy.
STUDY DESIGN Multicenter, randomized clinical pilot trial. STUDY POPULATION Critically ill patients, aged > 18 years, intubated for acute hypoxemic respiratory failure, and expected to receive ventilation for > 24 hours.
METHODS Patients are randomized to permissive lung-protective ventilation wherein RR is stepwise reduced, or to conventional lung-protective ventilation.
OUTCOME MEASURES The primary endpoint is feasibility, assessed by the difference in respiratory rate (RR) between the two groups, from the start of mechanical ventilation until first extubation. Secondary endpoints include protocol compliance and feasibility of collecting data, and safety, assessed by the occurrence of unacceptable hypercapnia and hypoxemia and the incidence of ventilator-associated complications SAMPLE SIZE To estimate the appropriate sample size for this pilot study, we considered the primary feasibility endpoint of detecting a difference in the respiratory rate (RR). Assuming an expected mean difference in RR of 7.5, based on previous studies [1, 2], with an SD of 10, a power of 90% and an alpha of 0.05, with a drop-out rate estimated at 10%, a two-tailed t-test was used. The required sample size is 84 patients (42 patients per group).
NATURE AND EXTENT OF THE BURDEN AND RISKS ASSOCIATED WITH PARTICIPATION, BENEFIT AND GROUP RELATEDNESS Ventilation with a lower RR may require permissive hypercapnia, which, when kept within safe limits, is safe. In current daily practice, there is no guidance in setting RR; consequently, RR varies widely across patients and is often set high. This pilot study compares two forms of lung-protective ventilation, both considered standard care in current ICU practice. The control group receives conventional ventilation with low tidal volumes and high RR to maintain normal PaCO₂ and pH. The intervention group, permissive ventilation, uses a lower RR to reduce mechanical power, accepting mild hypercapnia and acidosis. 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. We aim to evaluate this strategy more broadly in critically ill patients. The collection of demographic, 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Permissive lung-protective ventilation | Experimental | Other: Permissive lung-protective ventilationThe goal is to achieve the lowest possible respiratory rate (RR) according to a guideline < 1 hour after start of ventilation in the ICU. |
| Conventional lung-protective ventilation | Active comparator | Other: Conventional lung-protective ventilationThe respiratory rate is set according to standard of care < 1 hour after start of ventilation in the ICU. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- admission to one of the participating ICUs;
- intubated and receiving invasive ventilation with an expected duration of ventilation of at least 24 hours.
Key exclusion criteria (11 listed)
- age below 18 years;
- receiving invasive ventilation > 1 hour in the ICU, or receiving invasive ventilation > 6 hours directly preceding the current ICU admission (i.e., in the operating room or in the emergency department);
- receiving or planned to receive veno-venous, veno-arterial or arterio-venous extracorporeal membrane oxygenation (ECMO);
- having COPD GOLD III and IV;
- contra-indication 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 brain injury, judged by the attending physician;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Permissive lung-protective ventilationThe goal is to achieve the lowest possible respiratory rate (RR) according to a guideline in which the target RR is estimated by combining the baseline RR with the results of arterial blood gas analysis (ABG), determined by the highest acceptable partial pressure of carbon dioxide (PaCO2) of ≤ 8.5 kPa (64 mmHg) but limited by the lowest acceptable arterial pH (pHa) of > 7.20. The RR is gradually decreased, in steps of 2 breaths every 10 minutes, based on continuous end-tidal CO2 monitoring. To ensure that the pHa does not fall below 7.20, following randomization, ABGs are repeated every hour until the target RR is reached, for at least 6 hours. Thereafter, blood gas analyses are repeated at least every 8 hours (at the start of every nursing shift). Down-titration of RR stops at a rate of 4 breaths per minute. This approach continues until the switch to spontaneous breathing. Of note, when the pHa is > 7.50, this must first be decreased to ≤ 7.50 based on local protocol. | Other | Permissive lung-protective ventilation |
| Conventional lung-protective ventilationFollowing randomization, which should happen within 1 hour after start of ventilation in the ICU, the RR is set according to standard of care, based on continuous end-tidal CO2 monitoring, to target a normal PaCO2 (4.7-6.4 kPa or 35-48 mmHg) combined with a pHa within the range of 7.35 to 7.45. Following randomization, blood gas analyses are repeated every hour for at least 6 hours, and thereafter at least every 8 hours (at the start of every nursing shift). This approach continues until the weaning phase. | Other | Conventional lung-protective ventilation |
Primary outcome
Feasibility of the intervention
Time frame: from the start of mechanical ventilation until first extubation, up to 28 days
Assessed by the difference in respiratory rate (RR) between the two groups
4 secondary outcomes
Safety of the intervention
Time frame: From the start of mechanical ventilation until first extubation, up to 28 days.
Compliance of the protocol
Time frame: From the start of mechanical ventilation until first extubation, up to 28 days.
Compliance of the protocol
Time frame: from start of ventilation until first extubation, up to 28 days.
Feasibility of collecting data
Time frame: from start of mechanical ventilation until follow-up at day 90.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jul 2026.
- Derived from this study: PubMed 42754304Caroli A, Hoogenboom A, Bugedo G, Damiani FL, Ferreira J, Abreu MG, Geerts JW, Grady BP, List SS, van Meenen DMP, Morales-Quinteros L, Paulus F, Serpa Neto A, Schultz MJ, Slutsky AS, Sodhi K, Urlings-Strop L, Buiteman-Kruizinga LA; PERMISS collaborative group; PROVE network. Effects of PERMISSive lung-protective ventilation on outcome in critically ill, invasively ventilated patients (PERMISS): protocol for a feasibility and safety randomised clinical trial. BMJ Open Respir Res. 2026 Sep 17;13(1):e004532. doi: 10.1136/bmjresp-2026-004532.
- Individual participant dataSharing planned: Yes
Related trials for Mechanical Ventilation
Active, not recruiting
CT for Personalized Mechanical Ventilation
Ventilator-Induced Lung Injury, Sepsis Syndrome
Active, not recruitingObservational study
DIAPHRAGM STRENGTH AND LUNG VOLUMES
Mechanical Ventilation
Recruiting
Development and Preliminary Validation of Intelligent Video Laryngoscope for Emergency Use
Critically Ill Patients Requiring Mechanical Ventilation
Not yet recruiting
Mechanical Ventilator Adjustments and Patient Dyspnea
Respiratory Failure, Dyspnea During Mechanical Ventilation
Active, not recruitingObservational study
Potential Impact of the Use of the Application VentilO
Mechanical Ventilation Complication
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Laura Buiteman-Kruizinga, RN, PhD principal investigator
Reinier de Graaf Groep
Marcus J. Schultz, MD, PhD study chair
Amsterdam UMC
5 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Permissive lung-protective ventilation and Conventional lung-protective ventilation in people with Mechanical Ventilation and Intensive Care (ICU), run by Reinier de Graaf Groep at 5 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 8 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Netherlands, Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Laura A. Buiteman-Kruizinga, RN, PhD (+31152604040, l.kruizinga@rdgg.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Feasibility of the intervention (time frame: from the start of mechanical ventilation until first extubation, up to 28 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07077174, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jul 2026.