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Not yet recruitingNCT06912906BIWEANUpdated Apr 15, 2025

Feasibility Study to Compare Two Ventilatory Modes for Mechanical Ventilation Weaning

An interventional study of BIPAPasynchro: byphaisc positive pressure modality without any synchronisation in Mechanical Ventilation Weaning, sponsored by University of Lausanne Hospitals. Not yet recruiting at 2 sites in Switzerland. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-04-15.

Sponsored by University of Lausanne Hospitals · Not applicable, Interventional, and Supportive care

Phase
Not applicable
Study type
Interventional
Enrollment
84
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

We hypothesize that the ventilatory mode Bilevel Positive Airway Pressure without any synchronization (BIPAPasynchro) may facilitate the weaning process of patients intubated with acute hypoxiemic respiratory failure (AHRF) by obviating the problem of patient-ventilator asynchrony. In order to prove this hypothesis a large randomized controlled study should be perfromed comparing BIPAPasynchro versus pressure support ventilation (PSV), the most widely used ventilatory mode during the weaning process. In order to do so, a feasibility trial to demonstrate the ICU personnel can effectively use a non-standard ventilatory mode should be first performed. The objective of our study is, thus, to demonstrate the feasibility of using BIPAasynchro in the Lausanne Adult ICU.

Read the detailed description

Bilevel Positive Airway Pressure without any synchronization (BIPAPasynchro) ventilation is a ventilatory modality that guarantees a minimal mandatory minute ventilation, even in deeply sedated patients, and allows free spontaneous breathing as soon as possible, without requiring synchronization between the patient and the ventilator. The hypothesis is that, as it obviates the problem of patient-ventilator asynchrony, it could reduce, compared to pressure support ventilation (PSV), the need of sedation, decrease diaphragmatic atrophy and accelerate the liberation from mechanical ventilation (weaning phase) without exposing the patients to further risks. Data seems to suggest a potential benefit of BIPAPasynchro over PSV, but no large randomized controlled trials have been performed to compare the two techniques; however, this cannot be done after first demonstrating that it is feasible to use BIPAPasynchro in the weaning process from mechanical ventilation in the intensive care unit.

The present project aims at assessing the feasibility of using a standardized BIPAP weaning strategy. It is thus a feasibility trial that assesses the adherence to the use of the mode. It is a randomized trial with two parallel groups in which we will compare the percentage of time effectively spent in the assigned mode, either BIPAP asynchro (intervention group) or PSV (control group), since the first switch from assist-control ventilation to assisted ventilation.

The study primary endpoint is the percentage of patients who spent at least 65% of the time (a priori-chosen cut-off) in the assigned mode (either BIPAPasynchro or PSV mode) since the first switch to assisted ventilation until successful liberation from mechanical ventilation. Liberation from mechanical ventilation (successful weaning) is defined as follows: 1) for intubated patients, we consider the patient weaned from ventilation when extubated without reintubation within 72 hours. 2) For tracheostomized patients, we consider the patient weaned from ventilation as soon as ventilated less than 12h over 24h during three consecutive days.

The secondary endpoints are divided in other-feasibility endpoints, safety endpoints and exploratory endpoints.

The study secondary feasibility endpoints are:

  1. the proportions of participants who are switched to the non-assigned mode (cross-over from one study group to the other). Concretely, this refers to the situations where the patients in the PSV group are ventilated in BIPAPasynchro and the patients in the BIPAPasynchro group are ventilated in PSV.
  2. The percentage of time spent in the non-assigned ventilatory mode since patient inclusion;
  3. reasons for cross-over;
  4. physicians refusal rate of patient enrolment;
  5. reasons of physicians refusal if applicable;
  6. recruitment rates.

    Secondary safety endpoints

    The study secondary safety endpoints are:

  7. pneumothoraxes rate;
  8. unplanned extubation rate;
  9. rate of severe respiratory acidosis (pH \< 7.20);
  10. rate of severe respiratory alkalosis (pH > 7.55);
  11. ventilation acquired pneumonia (VAP) rate (13).

    Secondary exploratory endpoints

    The study secondary exploratory endpoints are:

  12. ventilator-free-days at day 28 from intubation (VFDs-28);
  13. ventilator-free-days at day 28 from randomization;
  14. duration of invasive mechanical ventilation between randomization and successful weaning, as defined in § 2.2.1;
  15. duration of invasive mechanical ventilation between randomization and successful weaning, defined as no reintubation (or reventilation) during 7 days after extubation
  16. number of tracheostomized patients during the weaning process;
  17. number of patients matching the criteria for difficult or prolonged weaning (14).
  18. length of ICU stay (censored at day 90 after randomization);
  19. ICU-free days at day 90 from randomization;
  20. length of Hospital stay (censored at day 90 from randomization);
  21. hospital-free days at day 90 from randomization;
  22. proportion of days with RASS less or equal -2 (for almost 50% of daily assessments) during invasive mechanical ventilation;
  23. proportion of days with sedation during invasive mechanical ventilation;
  24. proportion of days with neuromuscular blocking agents administration for ventilation facilitation during invasive mechanical ventilation;
  25. ICU mortality (censored at day 90 from randomization);
  26. hospital mortality (censored at day 90 from randomization).

This is a prospective, open-label, parallel-group, randomized feasibility trial taking place in the Adult ICU of the University Hospital of Lausanne, Switzerland. Due to the nature of the research, this is an open-label study. Patients will be randomized with a 1:1 ratio for receiving either BIPAPasynchro or PSV as soon as switching to assisted ventilation is considered as possible by the attending physician.

02

Conditions studied

  • Mechanical Ventilation Weaning
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Intubated ICU patient with acute respiratory failure;
  • PaO2-FiO2 ratio of less than 300 mmHg (40 kPa) at least one hour after intubation;
  • control or assist-control ventilation;
  • expected duration of mechanical ventilation of more than 24 hours;
  • clinician in charge considers that the patient can be switched to assisted ventilation (weaning phase start);
  • informed consent obtained by the patient himself / legal representative or authorization received from independent physician

Exclusion criteria

Exclusion Criteria:

  • less than 18 years old;
  • pregnant women (because of very different respiratory mechanics);
  • severe obesity (BMI > 40 kg/m2);
  • known obstructive pulmonary disease;
  • expected death within one week or very poor prognosis with end-of-life care decision expected/treatment withdrawal;
  • neurological disorders heavily influencing breathing pattern, like suspected or proven hypoxic brain injury, spinal injury above C8, severe traumatic brain injury, polyneuropathies (ex. Guillain-Barré, myasthenia gravis);
  • home non-invasive ventilation prior to ICU admission, except CPAP for obstructive sleeping apnoea syndrome;
  • tracheostomised at ICU admission;
  • suspected or proven broncho-pleural fistulas;
  • extracorporeal membrane oxygenation (ECMO) treatment;
  • ICU admission for major burns;
  • enrolment in other trial with competitive outcomes or treatment strategies;
  • Known opposition to research participation if patient is not able to consent (eg patient with refused GC)
04

Study design

Phase
Not applicable
Primary purpose
Supportive care
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
84 participants (estimated)

Study arms

  • No intervention
    Standard of care: Pressure support ventilation (PSV)

    Patient will be weaned from mechanical ventilation using the pressure support ventilation (PSV) modality accoring to the local standard of care.

  • Experimental
    Biphasic positive airway pressure without any synchronisation (BIPAPasynchro)

    Patients will be managed with byphaisc positive pressure modality without any synchronisation (BIPAPasynchro) as soon as they are considered to be ready to initiate the weaning phase from mechanical ventilation. Lausanne adult intesive care physicians will be provided a protocol to help guide them with the setting of BIPAPasynchro, as this is different from standard clinical pratice.

    Procedure: BIPAPasynchro: byphaisc positive pressure modality without any synchronisation

Interventions

  • ProcedureBIPAPasynchro: byphaisc positive pressure modality without any synchronisation

    Patients will be switched to byphaisc positive pressure modality without any synchronisation (BIPAPasynchro) as soon as they are considered to be ready to initiate the weaning phase from mechanical ventilation. Lausanne adult intesive care physicians will be provided a protocol to help guide them with the setting of BIPAPasynchro, as this is different from standard clinical pratice.

05

What researchers measure

Primary outcomes

  1. Percentage of time spent in the mode of assisted ventilation assigned by the randomization

    Time frame: From enrollement until liberation from mechanical ventilation or date of death, whichever comes first, assessed up to 90 days

Secondary outcomes

  1. The proportions of participants who are switched to the non-assigned mode (cross-over from one study group to the other)

    This refers to the situations where the patients in the PSV group are ventilated in BIPAPasynchro and the patients in the BIPAPasynchro group are ventilated in PSV.

    Time frame: From enrollement until liberation from mechanical ventilation or date of death, whichever comes first, assessed up to 90 days

  2. The percentage of time spent in the non-assigned ventilatory mode since patient inclusion

    Time frame: From enrollement until liberation from mechanical ventilation or date of death, whichever comes first, assessed up to 90 days

  3. Reasons for cross-over

    Reason why the patient is ventilated with another ventilatory mode compared to the one to which he was assigned at randomisation

    Time frame: From enrollement until liberation from mechanical ventilation or date of death, whichever comes first, assessed up to 90 days

  4. Physicians refusal rate of patient enrolment

    Time frame: At time of potential enrollement

  5. Reasons of physicians refusal if applicable

    Time frame: At time of potential enrollement

  6. Recruitment rates

    Time frame: At time of enrollment

  7. Pneumothoraxes rate

    Time frame: From enrollement until liberation from mechanical ventilation or date of death, whichever comes first, assessed up to 90 days

  8. Unplanned extubation rate

    Time frame: From enrollement until liberation from mechanical ventilaton or death, whichever comes first, assessed up to 90 days

  9. Rate of severe respiratory acidosis (pH < 7.20)

    Time frame: From enrollement until liberation from mechanical ventilation or date of death, whichever comes first, assessed up to 90 days

  10. Rate of severe respiratory alkalosis (pH > 7.55)

    Time frame: From enrollement until liberation from mechanical ventilation or date of death, whichever comes first, assessed up to 90 days

  11. Ventilation acquired pneumonia (VAP) rate

    Time frame: From enrollement until liberation from mechanical ventilation or date of death, whichever comes first, assessed up to 90 days

  12. Ventilator-free-days at day 28 from intubation

    Time frame: from intubation to 28 days after intubation

  13. Ventilator-free-days at day 28 from randomization

    Time frame: from randomization until 28 days after randomisation

  14. Duration of invasive mechanical ventilation between randomization and successful weaning

    Liberation from mechanical ventilation (successful weaning) is defined as follows: 1) for intubated patients, we consider the patient weaned from ventilation when extubated without reintubation within 72 hours. 2) For tracheostomized patients, we consider the patient weaned from ventilation as soon as ventilated less than 12h over 24h during three consecutive days.

    Time frame: from randomization until liberation from mechanical ventilation or death, whichever comes first, assessed up to 90 days

  15. Duration of invasive mechanical ventilation between randomization and successful weaning

    Successful weaning defined as no reintubation (or reventilation) during 7 days after extubation

    Time frame: from randomization until successful liberation from mechanical ventilation or death, whichever comes first, assessed up to up to 90 days

  16. Number of tracheostomized patients during the weaning process

    Time frame: From enrollement until liberation from mechanical ventilaton or death, whichever comes first, assessed up to 90 days

  17. Number of patients matching the criteria for difficult or prolonged weaning

    Difficult weaning defined as more than 1 day and less than 1 week and prolonged weaning defined as weaning duration of 1 week or more

    Time frame: From enrollement until liberation from mechanical ventilation or date of death, whichever comes first, assessed up to 90 days

  18. Length of ICU stay

    Time frame: from randomization until 90 days after randomization

  19. ICU-free days at day 90 from randomization

    Time frame: from randomization until 90 days after randomization

  20. Length of Hospital stay

    Time frame: from randomization until 90 days after randomization

  21. Hospital-free days at day 90 from randomization

    Time frame: from randomization until 90 days after randomization

  22. Proportion of days with RASS less or equal -2 (for almost 50% of daily assessments) during invasive mechanical ventilation;

    Time frame: from first intubation until liberation from mechanical ventilation or death, whichever comes first, assessed up to 90 days

  23. Proportion of days with sedation during invasive mechanical ventilation

    Time frame: from first intubation until liberation from mechanical ventilation or death, whichever comes first, assessed up to 90 days

  24. Proportion of days with neuromuscular blocking agents administration for ventilation facilitation during invasive mechanical ventilation

    Time frame: from first intubation until liberation from mechanical ventilation or death, whichever comes first, assessed up to 90 days

  25. ICU mortality

    Time frame: from randomization until 90 days after randomization

  26. Hospital mortality

    Time frame: from randomization until 90 days after randomization

06

Study locations

2 sites
  • University Hospital of Lausanne
    Lausanne, VD 1011, Switzerland
  • Lausanne University Hospital (CHUV)
    Lausanne, Switzerland
07

References and documents

Publications

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  • Rose L, Hawkins M. Airway pressure release ventilation and biphasic positive airway pressure: a systematic review of definitional criteria. Intensive Care Med. 2008 Oct;34(10):1766-73. doi: 10.1007/s00134-008-1216-3. Epub 2008 Jul 17. PubMed 18633595 ↗
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  • Jubran A, Grant BJ, Duffner LA, Collins EG, Lanuza DM, Hoffman LA, Tobin MJ. Effect of pressure support vs unassisted breathing through a tracheostomy collar on weaning duration in patients requiring prolonged mechanical ventilation: a randomized trial. JAMA. 2013 Feb 20;309(7):671-7. doi: 10.1001/jama.2013.159. PubMed 23340588 ↗
  • Boles JM, Bion J, Connors A, Herridge M, Marsh B, Melot C, Pearl R, Silverman H, Stanchina M, Vieillard-Baron A, Welte T. Weaning from mechanical ventilation. Eur Respir J. 2007 May;29(5):1033-56. doi: 10.1183/09031936.00010206. PubMed 17470624 ↗
  • Beduneau G, Pham T, Schortgen F, Piquilloud L, Zogheib E, Jonas M, Grelon F, Runge I, Nicolas Terzi, Grange S, Barberet G, Guitard PG, Frat JP, Constan A, Chretien JM, Mancebo J, Mercat A, Richard JM, Brochard L; WIND (Weaning according to a New Definition) Study Group and the REVA (Reseau Europeen de Recherche en Ventilation Artificielle) Network double dagger. Epidemiology of Weaning Outcome according to a New Definition. The WIND Study. Am J Respir Crit Care Med. 2017 Mar 15;195(6):772-783. doi: 10.1164/rccm.201602-0320OC. PubMed 27626706 ↗
  • Kalil AC, Metersky ML, Klompas M, Muscedere J, Sweeney DA, Palmer LB, Napolitano LM, O'Grady NP, Bartlett JG, Carratala J, El Solh AA, Ewig S, Fey PD, File TM Jr, Restrepo MI, Roberts JA, Waterer GW, Cruse P, Knight SL, Brozek JL. Management of Adults With Hospital-acquired and Ventilator-associated Pneumonia: 2016 Clinical Practice Guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Clin Infect Dis. 2016 Sep 1;63(5):e61-e111. doi: 10.1093/cid/ciw353. Epub 2016 Jul 14. PubMed 27418577 ↗
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  • Roshdy A, Elsayed AS, Saleh AS. Airway Pressure Release Ventilation for Acute Respiratory Failure Due to Coronavirus Disease 2019: A Systematic Review and Meta-Analysis. J Intensive Care Med. 2023 Feb;38(2):160-168. doi: 10.1177/08850666221109779. Epub 2022 Jun 22. PubMed 35733377 ↗
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  • Fredericks AS, Bunker MP, Gliga LA, Ebeling CG, Ringqvist JR, Heravi H, Manley J, Valladares J, Romito BT. Airway Pressure Release Ventilation: A Review of the Evidence, Theoretical Benefits, and Alternative Titration Strategies. Clin Med Insights Circ Respir Pulm Med. 2020 Feb 5;14:1179548420903297. doi: 10.1177/1179548420903297. eCollection 2020. PubMed 32076372 ↗
  • Yoshida T, Rinka H, Kaji A, Yoshimoto A, Arimoto H, Miyaichi T, Kan M. The impact of spontaneous ventilation on distribution of lung aeration in patients with acute respiratory distress syndrome: airway pressure release ventilation versus pressure support ventilation. Anesth Analg. 2009 Dec;109(6):1892-900. doi: 10.1213/ANE.0b013e3181bbd918. PubMed 19923518 ↗
  • Neumann P, Wrigge H, Zinserling J, Hinz J, Maripuu E, Andersson LG, Putensen C, Hedenstierna G. Spontaneous breathing affects the spatial ventilation and perfusion distribution during mechanical ventilatory support. Crit Care Med. 2005 May;33(5):1090-5. doi: 10.1097/01.ccm.0000163226.34868.0a. PubMed 15891341 ↗
  • Grassi A, Ferlicca D, Lupieri E, Calcinati S, Francesconi S, Sala V, Ormas V, Chiodaroli E, Abbruzzese C, Curto F, Sanna A, Zambon M, Fumagalli R, Foti G, Bellani G. Assisted mechanical ventilation promotes recovery of diaphragmatic thickness in critically ill patients: a prospective observational study. Crit Care. 2020 Mar 12;24(1):85. doi: 10.1186/s13054-020-2761-6. PubMed 32164784 ↗
  • Putensen C, Zech S, Wrigge H, Zinserling J, Stuber F, Von Spiegel T, Mutz N. Long-term effects of spontaneous breathing during ventilatory support in patients with acute lung injury. Am J Respir Crit Care Med. 2001 Jul 1;164(1):43-9. doi: 10.1164/ajrccm.164.1.2001078. PubMed 11435237 ↗
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  • Saddy F, Moraes L, Santos CL, Oliveira GP, Cruz FF, Morales MM, Capelozzi VL, de Abreu MG, Garcia CS, Pelosi P, Rocco PR. Biphasic positive airway pressure minimizes biological impact on lung tissue in mild acute lung injury independent of etiology. Crit Care. 2013 Oct 8;17(5):R228. doi: 10.1186/cc13051. PubMed 24103805 ↗
  • Saddy F, Oliveira GP, Garcia CS, Nardelli LM, Rzezinski AF, Ornellas DS, Morales MM, Capelozzi VL, Pelosi P, Rocco PR. Assisted ventilation modes reduce the expression of lung inflammatory and fibrogenic mediators in a model of mild acute lung injury. Intensive Care Med. 2010 Aug;36(8):1417-26. doi: 10.1007/s00134-010-1808-6. Epub 2010 Mar 24. PubMed 20333356 ↗

Individual participant data

Plan to share: No

08

Registry details

Key details

Study ID
NCT06912906
Lead sponsor
University of Lausanne Hospitals
Responsible party
Piquilloud Imboden Lise (Attending Physician, University of Lausanne Hospitals) — Principal investigator
First posted
Apr 6, 2025
Start date
Sep 1, 2025 (estimated)
Primary completion
Apr 15, 2027 (estimated)
Completion
Apr 15, 2027 (estimated)
Last update
Apr 15, 2025

Study contacts

Lise Piquilloud Imboden
Contact
lise.piquilloud@chuv.ch
+41795566827

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
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