PRactice of VENTilation in COVID-19 Patients (PRoVENT-COVID) (PRoVENT-COVID)

PRactice of VENTilation in COVID-19 Patients (PRoVENT-COVID) - an Observational Study of Invasively Ventilated Patients in the Netherlands

The purpose of this national, multicenter service review is to determine and compare ventilation management in COVID-19 patients in the Netherlands, and to determine whether certain ventilation settings have an independent association with duration of ventilation.

In every adult invasively ventilated COVID-19 patient from a participating ICU, granular ventilator settings and parameters will be collected from start of invasive ventilation for up to 72 hours. Follow up is until ICU and hospital discharge, and until day 90. The primary outcome includes main ventilator settings (including tidal volume, airway pressures, oxygen fraction and respiratory rate). Secondary endpoints are ventilator-free days and alive at day 28 (VFD-28); duration of mechanical ventilation; use of prone positioning and recruitment maneuvers; duration of ICU and hospital stay; incidence of kidney injury; and ICU, hospital, 28-day and 90-day mortality.

Study Overview

• Status: Completed
• Conditions: COVID; Acute Respiratory Failure; Mechanical Ventilation

Detailed Description

Rationale:

The novel coronavirus disease (COVID-19) pandemic is rapidly expanding across the world, with over 60.000 new cases each day as of late March 2020. Healthcare workers are struggling to provide the best care for patients with proven or suspected COVID-19. Approaches for clinical care vary widely between and within countries and new insights are acquired rapidly. This includes the way invasive ventilation is applied.

Objective:

To determine and compare invasive ventilation settings and parameters in COVID-19 patients in the Netherlands, and to determine associations with clinical outcomes.

Hypotheses:

Invasive ventilation settings and parameters vary between intensive care units (ICUs) in hospitals in the Netherlands; certain ventilator settings have an independent association with duration of ventilation in COVID-19 patients.

Study design:

Multicenter, national, retrospective, observational study in COVID-19 patients with respiratory failure, requiring invasive ventilation in intensive care unit (ICU) in hospitals in the Netherlands.

Study population:

The data of at least 1,000 consecutively invasively ventilated COVID-19 patients admitted to intensive care units (ICUs) of hospitals in the Netherlands. This study will not be restricted to the 'formal' ICUs, as patients may also receive invasive ventilation in other locations within the hospital during the COVID-19 pandemic.

Methods:

In every patient, granular ventilator settings and parameters are collected from start of invasive ventilation for up to 72 hours. Patients will be followed up until ICU and hospital discharge, and until day 90.

Sample size calculation:

No formal sample size calculation is needed. We expect to capture at least 1,000 patients, but will continue collecting data of new patients for at least 8 weeks.

Study endpoints:

Main ventilator settings (including tidal volume, airway pressures, oxygen fraction and respiratory rate) (primary) and parameters (blood gas results); use of rescue therapies (including prone positioning); use of sedatives, vasopressors and inotropes; daily cumulative fluid balances; development of kidney injury; ventilator-free days and alive at day 28 (VFD-28), duration of ICU and hospital stay, and ICU, hospital and 90-day mortality.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness:

Retrospective collection of data regarding ventilation management and major clinical endpoints is without risk for the individual patient.

• Study Type: Observational
• Enrollment (Actual): 1122

Contacts and Locations

Study Locations

• Netherlands
  • Almere, Netherlands
    • Flevoziekenhuis
  • Amsterdam, Netherlands
    • Onze Lieve Vrouwe Gasthuis
  • Amsterdam, Netherlands
    • Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
  • Apeldoorn, Netherlands
    • Gelre Ziekenhuizen
  • Arnhem, Netherlands
    • Rijnstate Ziekenhuis
  • Breda, Netherlands
    • Amphia Ziekenhuis
  • Delft, Netherlands
    • Reinier de Graaf Gasthuis
  • Den Haag, Netherlands
    • Haaglanden Medisch Centrum
  • Den Haag, Netherlands
    • HagaZiekenhuis
  • Ede, Netherlands
    • Ziekenhuis Gelderse Vallei
  • Eindhoven, Netherlands
    • Catharina Ziekenhuis
  • Eindhoven, Netherlands
    • Maxima Medical Center
  • Geldrop, Netherlands
    • St Anna ziekenhuis
  • Groningen, Netherlands
    • Universitair Medisch Centrum Groningen
  • Haarlem, Netherlands
    • Spaarne Gasthuis
  • Hoorn, Netherlands
    • Dijklander ziekenhuis
  • Leeuwarden, Netherlands
    • Leeuwarden Medisch Centrum
  • Maastricht, Netherlands
    • Maastricht Universitair Medisch Centrum
  • Nieuwegein, Netherlands
    • St Antonius Ziekenhuis
  • Rotterdam, Netherlands
    • Maasstad Hospital
  • Sittard, Netherlands
    • Zuyderland Medisch Centrum
  • Zwolle, Netherlands
    • Isala Ziekenhuis

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Invasively ventilated patients with COVID-19.

Description

Inclusion Criteria:

• COVID-19, confirmed with polymerase chain reaction (PCR) and/or presence of typical abnormalities on chest computer tomography (CT)
• Suspected COVID-19 infection, with no exclusion of diagnosis
• Having received invasive ventilation

Exclusion Criteria:

• Age <18 years
• Already included in the same study in another hospital
• Having had received invasive ventilation > 24 hours in a non-participating hospital

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Mechanical ventilation; COVID patients receiving invasive mechanical ventilation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Ventilation Mode	Day 1 to Day 3 from initiation of mechanical ventilation
Tidal volume set	Day 1 to Day 3 from initiation of mechanical ventilation
Expiratory tidal volume	Day 1 to Day 3 from initiation of mechanical ventilation
Positive end-expiratory pressure	Day 1 to Day 3 from initiation of mechanical ventilation
Maximum airway pressure or plateau pressure (P plateau) or peak pressure (P peak) (cm H2O);	Day 1 to Day 3 from initiation of mechanical ventilation
Level of pressure support above positive end-expiratory pressure (PEEP)	Day 1 to Day 3 from initiation of mechanical ventilation
Inspired fraction of oxygen	Day 1 to Day 3 from initiation of mechanical ventilation
Set and measured respiratory rate	Day 1 to Day 3 from initiation of mechanical ventilation
Inspiration to expiration ratio	Day 1 to Day 3 from initiation of mechanical ventilation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of ventilation-free days and alive at day 28		Until 28 days from initiation of mechanical ventilation
Duration of ventilation in survivors;	time between start invasive ventilation and successful extubation in survivors	Until 28 days from initiation of mechanical ventilation
Use of prone positioning		Day 1 to Day 3 from initiation of mechanical ventilation
Use of recruitment maneuvers		Day 1 to Day 3 from initiation of mechanical ventilation
Incidence of acute kidney injury		Until 28 days from initiation of mechanical ventilation
Duration of ICU stay	Time between admission and discharge ICU or death in ICU	Until 28 days from initiation of mechanical ventilation
Duration of hospital stay	Time between admission and discharge from hospital or death in hospital	Until 28 days from initiation of mechanical ventilation
ICU mortality	Any death during ICU stay	Until 28 days from initiation of mechanical ventilation
Hospital mortality	Any death during hospital stay	Until 28 days from initiation of mechanical ventilation
28-day mortality		Until 28 days from initiation of mechanical ventilation
90-day mortality		Until 90 days from initiation of mechanical ventilation

Collaborators and Investigators

• Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Investigators: Principal Investigator: Marcus Schultz, MD, PhD, Department of Intensive Care, Academic Medical Center, University of Amsterdam; Study Chair: Frederique Paulus, PhD, Department of Intensive Care, Academic Medical Center, University of Amsterdam; Study Chair: Ary Serpa Neto, MD, PhD, Department of Intensive Care, Academic Medical Center, University of Amsterdam; Study Director: Anna Geke Algera, MD, Department of Intensive Care, Academic Medical Center, University of Amsterdam; Study Director: Anissa Tsonas, MD, Department of Intensive Care, Academic Medical Center, University of Amsterdam; Study Director: Michela Botta, MD, Department of Intensive Care, Academic Medical Center, University of Amsterdam

Publications and helpful links

General Publications

• Ahuja S, de Grooth HJ, Paulus F, van der Ven FL, Serpa Neto A, Schultz MJ, Tuinman PR; PRoVENT-COVID Study Collaborative Group* 'PRactice of VENTilation in COVID-19'. Association between early cumulative fluid balance and successful liberation from invasive ventilation in COVID-19 ARDS patients - insights from the PRoVENT-COVID study: a national, multicenter, observational cohort analysis. Crit Care. 2022 Jun 1;26(1):157. doi: 10.1186/s13054-022-04023-y.
• Schuijt MTU, van Meenen DMP, Martin-Loeches I, Mazzinari G, Schultz MJ, Paulus F, Serpa Neto A. Association of Time-Varying Intensity of Ventilation With Mortality in Patients With COVID-19 ARDS: Secondary Analysis of the PRoVENT-COVID Study. Front Med (Lausanne). 2021 Nov 18;8:725265. doi: 10.3389/fmed.2021.725265. eCollection 2021.
• Bos LDJ, Sjoding M, Sinha P, Bhavani SV, Lyons PG, Bewley AF, Botta M, Tsonas AM, Serpa Neto A, Schultz MJ, Dickson RP, Paulus F; PRoVENT-COVID collaborative group. Longitudinal respiratory subphenotypes in patients with COVID-19-related acute respiratory distress syndrome: results from three observational cohorts. Lancet Respir Med. 2021 Dec;9(12):1377-1386. doi: 10.1016/S2213-2600(21)00365-9. Epub 2021 Oct 13. Erratum In: Lancet Respir Med. 2021 Dec;9(12):e114.
• Schuijt MTU, Schultz MJ, Paulus F, Serpa Neto A; PRoVENT-COVID Collaborative Group. Association of intensity of ventilation with 28-day mortality in COVID-19 patients with acute respiratory failure: insights from the PRoVENT-COVID study. Crit Care. 2021 Aug 6;25(1):283. doi: 10.1186/s13054-021-03710-6.
• Valk CMA, Tsonas AM, Botta M, Bos LDJ, Pillay J, Serpa Neto A, Schultz MJ, Paulus F; Writing Committee for the PRoVENT-COVID * Collaborative Group. Association of early positive end-expiratory pressure settings with ventilator-free days in patients with coronavirus disease 2019 acute respiratory distress syndrome: A secondary analysis of the Practice of VENTilation in COVID-19 study. Eur J Anaesthesiol. 2021 Dec 1;38(12):1274-1283. doi: 10.1097/EJA.0000000000001565.
• Boers NS, Botta M, Tsonas AM, Algera AG, Pillay J, Dongelmans DA, Horn J, Vlaar APJ, Hollmann MW, Bos LDJ, Paulus F, Neto AS, Schultz MJ; PRoVENT-COVID investigatorsdagger. PRactice of VENTilation in Patients with Novel Coronavirus Disease (PRoVENT-COVID): rationale and protocol for a national multicenter observational study in The Netherlands. Ann Transl Med. 2020 Oct;8(19):1251. doi: 10.21037/atm-20-5107.
• Botta M, Tsonas AM, Pillay J, Boers LS, Algera AG, Bos LDJ, Dongelmans DA, Hollmann MW, Horn J, Vlaar APJ, Schultz MJ, Neto AS, Paulus F; PRoVENT-COVID Collaborative Group. Ventilation management and clinical outcomes in invasively ventilated patients with COVID-19 (PRoVENT-COVID): a national, multicentre, observational cohort study. Lancet Respir Med. 2021 Feb;9(2):139-148. doi: 10.1016/S2213-2600(20)30459-8. Epub 2020 Oct 23.

Study record dates

Study Major Dates

• Study Start (Actual): March 6, 2020
• Primary Completion (Actual): September 1, 2020
• Study Completion (Actual): September 1, 2020

Study Registration Dates

• First Submitted: April 9, 2020
• First Submitted That Met QC Criteria: April 14, 2020
• First Posted (Actual): April 15, 2020

Study Record Updates

• Last Update Posted (Actual): July 6, 2021
• Last Update Submitted That Met QC Criteria: July 1, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: COVID
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Respiratory Insufficiency
• Other Study ID Numbers: PRoVENT-COVID

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No