NCT03167580

Brief Summary

The 'REstricted versus Liberal positive end-expiratory pressure in patients without Acute respiratory distress syndrome' (RELAx) trial is a national multicenter, open randomized controlled trial in ICU patients without ARDS at start of ventilation. It will be the first RCT comparing ventilation with the lowest possible positive end-expiratory pressure (PEEP) level with ventilation with the median PEEP level currently practiced in the Netherlands that recruits a sufficient number of patients to test the hypothesis that ventilation with the lowest possible PEEP level is non-inferior to ventilation with a PEEP level of 8 cm H2O with regard to objective and patient-relevant clinical endpoints.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
980

participants targeted

Target at P75+ for not_applicable

Timeline
Completed

Started Oct 2017

Typical duration for not_applicable

Geographic Reach
1 country

13 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

May 23, 2017

Completed
7 days until next milestone

First Posted

Study publicly available on registry

May 30, 2017

Completed
5 months until next milestone

Study Start

First participant enrolled

October 26, 2017

Completed
2.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 14, 2020

Completed
2 months until next milestone

Study Completion

Last participant's last visit for all outcomes

March 16, 2020

Completed
Last Updated

March 31, 2020

Status Verified

March 1, 2020

Enrollment Period

2.2 years

First QC Date

May 23, 2017

Last Update Submit

March 30, 2020

Conditions

Ventilator-free Days

Outcome Measures

Primary Outcomes (1)

  • Ventilation-free days and alive at day 28

    The number of ventilation-free days, defined as the number of days from day 1 to day 28; the patient is alive and breathes without assistance of the mechanical ventilator, if the period of unassisted breathing lasted at least 24 consecutive hours.

    first 28 days after start of ventilation

Secondary Outcomes (7)

  • Length of stay

    first 90 days after start of ventilation

  • Mortality

    first 90 days after start of ventilation

  • Pulmonary complications

    daily until detubation or day 28

  • Rescue strategies for severe hypoxemia or severe atelectasis

    daily until detubation or day 28

  • Days with use of hemodynamic support

    daily until detubation or day 28

  • +2 more secondary outcomes

Study Arms (2)

Ventilation with restricted PEEP level

EXPERIMENTAL

Use of the restricted PEEP level (0 - 5 cm H2O, the lowest possible PEEP level) after intubation and during all mechanical ventilation.

Procedure: restricted PEEP

Ventilation with liberal PEEP Level

ACTIVE COMPARATOR

Use of the liberal PEEP level (8 cm H2O) after intubation and during all mechanical ventilation.

Procedure: liberal PEEP

Interventions

restricted PEEPPROCEDURE

Patients are randomized and ventilated with restricted PEEP (the lowest possible PEEP level, 0 - 5 cm H2O)

Ventilation with restricted PEEP level
liberal PEEPPROCEDURE

Patients are randomized and ventilated with liberal PEEP (the median PEEP level used in the Netherlands, 8 cm H2O)

Ventilation with liberal PEEP Level

Eligibility Criteria

Age18 Years - 100 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Admission to one of the participating ICUs
  • Need for and start of invasive ventilation
  • An expected duration of ventilation \> 24 hours

You may not qualify if:

  • Age less than 18 years
  • Patients with a clinical diagnosis of ARDS or possible ARDS with a PaO2/FiO2 \< 200 mmHg (as the benefit of ventilation with higher PEEP levels has been proven in these patients)
  • Patients with ongoing cardiac ischemia due to cardiac infarction and failed revascularization, patients with increased and uncontrollable intracranial pressure (of ≥ 18 mmHg), patients with delayed cerebral ischemia after subarachnoid hemorrhage, patients with necrotizing fasciitis, and severe untreatable anemia such as in case of Jehovah's Witnesses (as these patients can be considered to be vulnerable to the potentially dangerous hypoxemia which could develop more often, even for a short time, in the 'restricted PEEP'-arm of this trial)
  • Patients previously randomized in this RCT
  • Patients participating in another RCT with the same clinical endpoint, or interventions possibly compromising the primary outcome
  • Invasive ventilation longer than 12 hours directly preceding the present ICU admission
  • Invasive ventilation longer than 1 hour before randomization
  • Patients with suspected or confirmed pregnancy
  • Patients with morbid obesity (body mass index \> 40)
  • Patients with GOLD classification III or IV chronic obstructive pulmonary disease (COPD)
  • Patients with premorbid restrictive pulmonary disease (evidence of chronic interstitial infiltration on chest radiographs)
  • Patients in whom pulse oximetry is known to be unreliable, e.g., patients with carbon monoxide poisoning
  • Any neurologic diagnosis that can prolong duration of mechanical ventilation, e.g., patients with Guillain-Barré syndrome, high spinal cord lesion or amyotrophic lateral sclerosis, multiple sclerosis, or myasthenia gravis
  • No informed consent

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (13)

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Amsterdam, Netherlands

Location

Onze Lieve Vrouwe Gasthuis

Amsterdam, Netherlands

Location

VU Medical Center

Amsterdam, Netherlands

Location

Gelre Hospital

Apeldoorn, Netherlands

Location

Rijnstate

Arnhem, Netherlands

Location

Amphia Hospital

Breda, Netherlands

Location

Spaarne Gasthuis

Hoofddorp, Netherlands

Location

Westfriesgasthuis

Hoorn, Netherlands

Location

Maastricht University Medical Center

Maastricht, Netherlands

Location

Sint Antonius Hospital

Nieuwegein, Netherlands

Location

Haaglanden Medical Center

The Hague, Netherlands

Location

HagaZiekenhuis

The Hague, Netherlands

Location

Isala Clinics

Zwolle, Netherlands

Location

Related Publications (3)

  • van Meenen DMP, Algera AG, Schuijt MTU, Simonis FD, van der Hoeven SM, Neto AS, Abreu MG, Pelosi P, Paulus F, Schultz MJ; for the NEBULAE; PReVENT; RELAx investigators. Effect of mechanical power on mortality in invasively ventilated ICU patients without the acute respiratory distress syndrome: An analysis of three randomised clinical trials. Eur J Anaesthesiol. 2023 Jan 1;40(1):21-28. doi: 10.1097/EJA.0000000000001778. Epub 2022 Nov 18.

    PMID: 36398740DERIVED

  • Writing Committee and Steering Committee for the RELAx Collaborative Group; Algera AG, Pisani L, Serpa Neto A, den Boer SS, Bosch FFH, Bruin K, Klooster PM, Van der Meer NJM, Nowitzky RO, Purmer IM, Slabbekoorn M, Spronk PE, van Vliet J, Weenink JJ, Gama de Abreu M, Pelosi P, Schultz MJ, Paulus F. Effect of a Lower vs Higher Positive End-Expiratory Pressure Strategy on Ventilator-Free Days in ICU Patients Without ARDS: A Randomized Clinical Trial. JAMA. 2020 Dec 22;324(24):2509-2520. doi: 10.1001/jama.2020.23517.

    PMID: 33295981DERIVED

  • Algera AG, Pisani L, Bergmans DCJ, den Boer S, de Borgie CAJ, Bosch FH, Bruin K, Cherpanath TG, Determann RM, Dondorp AM, Dongelmans DA, Endeman H, Haringman JJ, Horn J, Juffermans NP, van Meenen DM, van der Meer NJ, Merkus MP, Moeniralam HS, Purmer I, Tuinman PR, Slabbekoorn M, Spronk PE, Vlaar APJ, Gama de Abreu M, Pelosi P, Serpa Neto A, Schultz MJ, Paulus F; RELAx Investigators and the PROVE Network Investigators. RELAx - REstricted versus Liberal positive end-expiratory pressure in patients without ARDS: protocol for a randomized controlled trial. Trials. 2018 May 9;19(1):272. doi: 10.1186/s13063-018-2640-5.

    PMID: 29739430DERIVED

Related Links

Study Officials

  • Marcus J. Schultz, MD, PhD

    Department of Intensive Care, Academic Medical Center

    PRINCIPAL INVESTIGATOR

  • Frederique Paulus, PhD

    Department of Intensive Care, Academic Medical Center

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
NONE
Masking Details
Open Label
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: Parallel Assignment
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Prof. Dr. Marcus J. Schultz

Study Record Dates

First Submitted

May 23, 2017

First Posted

May 30, 2017

Study Start

October 26, 2017

Primary Completion

January 14, 2020

Study Completion

March 16, 2020

Last Updated

March 31, 2020

Record last verified: 2020-03

Locations

NL(13)