Early Non-invasive Ventilation Outside the Intensive Care Unit (NAVIGATE)

Reducing the Need for Intensive Care Unit in Hospitalized Patients With Early Respiratory Failure Using the Non-invasive Ventilation Technique. A Multicentre Randomized Study.

A large multicentre, randomized, controlled trial to demonstrate that non invasive ventilation given at an early stage of acute respiratory failure (ARF) outside the intensive care unit (ICU) can prevent the deterioration of ARF and the need for ICU when compared to the best available treatment usually performed in the non-ICU wards.

Study Overview

• Status: Completed
• Conditions: Early Acute Respiratory Failure
• Intervention / Treatment: Other: Standard care; Procedure: Non-invasive ventilation

• Study Type: Interventional
• Enrollment (Actual): 520
• Phase: Phase 4

Contacts and Locations

Study Locations

• Greece
  • Larissa, Greece
    • University of Thessaly
• Italy
  • Asti, Italy
    • Ospedale Civile di Asti
  • Brescia, Italy
    • Spedali Civili
  • Genova, Italy
    • Ospedali Galliera
  • Genova, Italy
    • ASL 3 Genovese
  • Pisa, Italy
    • AOU Pisana
  • Reggio Calabria, Italy
    • Grande Ospedale Metropolitano
  • Roma, Italy
    • Policlinico A. Gemelli
  • Roma, Italy
    • Aurelia Hospital
  • Torino, Italy
    • Azienda Ospedaliera San Giovanni Battista Molinette
  • MI
    • Milan, MI, Italy, 20132
      • Ospedale San Raffaele di Milano
  • Piemonte
    • Alessandria, Piemonte, Italy, 15121
      • Ospedale Cesare Arrigo
    • Novara, Piemonte, Italy
      • Ospedale di Novara
• Kazakhstan
  • Kazakhstan, Kazakhstan
    • Astana Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Informed consent
• Age >= 18 years
• Admission in a non-intensive-care department
• Radiological evidence of new pulmonary consolidation or atelectasis
• Peripheral Oxygen saturation less than 92% while breathing room air or PaO2/FiO2 ratio less than 300 at blood gas analysis
• Decompensated hypercapnia (pCO2 > 45 mmHg and pH < 7.35)
• Clinical signs of respiratory distress (dyspnoea, utilization of accessory respiratory muscles, paradox movements of thoraco-abdominal wall) in air.

Exclusion Criteria:

• Respiratory failure due to chronic obstructive pulmonary disease exacerbation, defined as PaCO2 > 45 and pH < 7.35 (in these patients NIV is considered to be the standard/first line treatment and we do not want to deny these patients the opportunity to receive this treatment because of randomization)
• Severe, hypercapnic ARF defined as PaCO2 > 45 and pH < 7.30
• Severe, hypoxic ARF defined as PaO2/FiO2 < 200
• Need for immediate mechanical ventilation or ICU as judged by the ICU physician in charge
• Extremely poor short term prognosis (imminent death with decision for palliative treatment only)
• Invasive or non-invasive mechanical ventilation during the same hospitalization due to respiratory failure.
• Clear contraindication to NIV treatment: respiratory arrest, failure to correct positioning of a face mask, hemodynamic instability due to hypotensive shock, ongoing myocardial ischemia, arrhythmia, massive bleeding from upper gastrointestinal tract, patient uncooperative and upset, inability to protect airways, alterations of deglutition, inability to clear secretion also with external aspiration, multiple organs dysfunction, recent surgery of airways or upper gastrointestinal tract, not-drained pneumothorax, bowel obstruction, active vomit.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NIV; Non-invasive ventilation	Procedure: Non-invasive ventilation; Early non-invasive ventilation will be given to patients at an early stage of acute respiratory failure; Other Names: NIV; Noninvasive ventilation
Other: Best available treatment	Other: Standard care

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of patients who will need admission to the Intensive Care Unit care for severe acute respiratory failure	participants will be followed for the duration of hospital stay, an expected average of 2 weeks

Collaborators and Investigators

• Sponsor: Università Vita-Salute San Raffaele

Publications and helpful links

General Publications

• Cabrini L, Nobile L, Plumari VP, Landoni G, Borghi G, Mucchetti M, Zangrillo A. Intraoperative prophylactic and therapeutic non-invasive ventilation: a systematic review. Br J Anaesth. 2014 Apr;112(4):638-47. doi: 10.1093/bja/aet465. Epub 2014 Jan 19.
• Cabrini L, Plumari VP, Nobile L, Olper L, Pasin L, Bocchino S, Landoni G, Beretta L, Zangrillo A. Non-invasive ventilation in cardiac surgery: a concise review. Heart Lung Vessel. 2013;5(3):137-41.
• Cabrini L, Brusasco C, Roasio A, Corradi F, Nardelli P, Filippini M, Cotticelli V, Belletti A, Ferrera L, Antonucci E, Baiardo Redaelli M, Lattuada M, Colombo S, Olper L, Ponzetta G, Ananiadou S, Monti G, Severi L, Maj G, Giardina G, Biondi-Zoccai G, Benedetto U, Gemma M, Cavallero SSM, Hajjar LA, Zangrillo A, Bellomo R, Landoni G. Non-invAsive VentIlation for early General wArd respiraTory failurE (NAVIGATE): A multicenter randomized controlled study. Protocol and statistical analysis plan. Contemp Clin Trials. 2019 Mar;78:126-132. doi: 10.1016/j.cct.2019.02.001. Epub 2019 Feb 7.
• Monti G, Cabrini L, Kotani Y, Brusasco C, Kadralinova A, Giardina G, Chalkias A, Nakhnoukh C, Pantazopoulos I, Oliva FM, Dazzi F, Roasio A, Baiardo Redaelli M, Tripodi VF, Cucciolini G, Belletti A, Vaschetto R, Maj G, Borghi G, Savelli F, Boni S, D'Amico F, Cavallero S, Labanca R, Tresoldi M, Marmiere M, Marzaroli M, Moizo E, Monaco F, Nardelli P, Pieri M, Plumari V, Scandroglio AM, Turi S, Corradi F, Konkayev A, Landoni G, Bellomo R, Zangrillo A; NAVIGATE Study Group. Early noninvasive ventilation in general wards for acute respiratory failure: an international, multicentre, open-label, randomised trial. Br J Anaesth. 2025 Feb;134(2):382-391. doi: 10.1016/j.bja.2024.11.023. Epub 2025 Jan 2.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2012
• Primary Completion (Actual): August 17, 2023
• Study Completion (Actual): July 18, 2024

Study Registration Dates

• First Submitted: March 16, 2012
• First Submitted That Met QC Criteria: April 3, 2012
• First Posted (Estimated): April 6, 2012

Study Record Updates

• Last Update Posted (Actual): August 7, 2025
• Last Update Submitted That Met QC Criteria: August 5, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: hypoxia; NIV; non-invasive ventilation; acute respiratory failure; hypercapnia; hospital ward
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Respiratory Insufficiency
• Other Study ID Numbers: VP/96/ER/mm