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A Randomised Controlled Trial of High-Flow Nasal Oxygen Versus Standard Oxygen Therapy in Critically Ill Immunocompromised Patients (HIGH)

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ClinicalTrials.gov Identifier: NCT02739451
Recruitment Status : Completed
First Posted : April 15, 2016
Last Update Posted : July 24, 2018
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

Tracking Information
First Submitted Date  ICMJE March 29, 2016
First Posted Date  ICMJE April 15, 2016
Last Update Posted Date July 24, 2018
Study Start Date  ICMJE May 2016
Actual Primary Completion Date December 31, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 11, 2016)
All-cause day-28 mortality [ Time Frame: 28 days ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02739451 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 17, 2016)
  • Intubation or reintubation rate [ Time Frame: days 3 and 28 ]
    proportion of patients requiring invasive mechanical ventilation
  • patient comfort [ Time Frame: 28 days ]
    Visual Analogue Scale (VAS) score
  • Intensity of dyspnoea [ Time Frame: days 1-3 ]
    Visual Analogue Scale (VAS) score
  • Perceived Exertion [ Time Frame: days 1-3 ]
    Borg scale
  • Respiratory rate [ Time Frame: days 1-3 ]
  • Oxygenation [ Time Frame: days 1-3 ]
    based on continuous saturation of peripheral oxygen (SpO2) monitoring, lowest SpO2 from D1 to D3 and PaO2/FiO2 on D1, D2, and D3
  • ICU length of stay [ Time Frame: 28 days ]
  • Incidence of ICU-acquired infections [ Time Frame: 28 days ]
  • Time to clear pulmonary infiltrates [ Time Frame: 28 days ]
    Murray score
  • Oxygen-free and ventilation-free survivals [ Time Frame: day 28 ]
  • Re-intubation rate [ Time Frame: day 28 ]
  • Lowest median SpO2 during intubation [ Time Frame: days 1-3 ]
    for patients who were intubated during the study period
  • Repartition of acute mild/moderate/severe respiratory distress syndrome (ARDS) stages after intubation or reintubation as defined by the Berlin definition [ Time Frame: day 28 ]
  • Hypoxemic cardiac arrests [ Time Frame: day 28 ]
    After discussion at the investigator meeting and based on comments from the Data and Safety Monitoring Board on May 12, 2016, all hypoxemic cardiac arrests will be considered as suspected unexpected serious adverse reaction
Original Secondary Outcome Measures  ICMJE
 (submitted: April 11, 2016)
  • Intubation or reintubation rate [ Time Frame: days 3 and 28 ]
    proportion of patients requiring invasive mechanical ventilation
  • patient comfort [ Time Frame: 28 days ]
    Visual Analogue Scale (VAS) score
  • Intensity of dyspnoea [ Time Frame: days 1-3 ]
    Visual Analogue Scale (VAS) score
  • Perceived Exertion [ Time Frame: days 1-3 ]
    Borg scale
  • Respiratory rate [ Time Frame: days 1-3 ]
  • Oxygenation [ Time Frame: days 1-3 ]
    based on continuous saturation of peripheral oxygen (SpO2) monitoring, lowest SpO2 from D1 to D3 and PaO2/FiO2 on D1, D2, and D3
  • ICU length of stay [ Time Frame: 28 days ]
  • Incidence of ICU-acquired infections [ Time Frame: 28 days ]
  • Time to clear pulmonary infiltrates [ Time Frame: 28 days ]
    Murray score
  • Oxygen-free and ventilation-free survivals [ Time Frame: day 28 ]
  • Re-intubation rate [ Time Frame: day 28 ]
  • Lowest median SpO2 during intubation [ Time Frame: days 1-3 ]
    for patients who were intubated during the study period
  • Repartition of acute mild/moderate/severe respiratory distress syndrome (ARDS) stages after intubation or reintubation as defined by the Berlin definition [ Time Frame: day 28 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Randomised Controlled Trial of High-Flow Nasal Oxygen Versus Standard Oxygen Therapy in Critically Ill Immunocompromised Patients
Official Title  ICMJE A Randomised Controlled Trial of High-Flow Nasal Oxygen Versus Standard Oxygen Therapy in Critically Ill Immunocompromised Patients
Brief Summary

Acute respiratory failure (ARF) is the leading reason for ICU admission in immunocompromised patients. Usual oxygen therapy involves administering low-to-medium oxygen flows through a nasal cannula or mask [with or without a bag and with or without the Venturi system] to achieve SpO2≥95%.

Oxygen therapy may be combined with non-invasive ventilation [NIV] providing both end-expiratory positive pressure and pressure support. However, in a recent trial by our group, non-invasive ventialtion [NIV] was not superior over oxygen without NIV.

High-flow nasal oxygen [HFNO] therapy is a focus of growing attention as an alternative to standard oxygen therapy. By providing warmed and humidified gas, HFNO allows the delivery of higher flow rates [of up to 60 L/min] via nasal cannula devices, with Fraction of inspired oxygen (FiO2) values of nearly 100%. Physiological benefits of HFNO consist of higher and constant FiO2 values, decreased work of breathing, nasopharyngeal washout leading to improved breathing-effort efficiency, and higher positive airway pressures associated with better lung recruitment.

Clinical consequences of these physiological benefits include alleviation of dyspnoea and discomfort, decreases in tachypnoea and signs of respiratory distress, a diminished need for intubation in patients with severe hypoxemia, and decreased mortality in unselected patients with acute hypoxemic respiratory failure However, although preliminary data establish the feasibility and safety of this technique, HFNO has never been properly evaluated in immunocompromised patients.

Thus, this project aims at demonstrating that HFNO is superior to low/medium-flow (standard) oxygen, minimising day-28 mortality

Detailed Description

After discussion at the investigator meeting and based on comments from the Data and Safety Monitoring Board on May 12, 2016, the DSMB has highlighted the need of the interim analysis (already planned) as benefits from high flow oxygen may be observed after 400 inclusions.

Update on June 16, 2017:

The number of patients enrolled is 488 and the inclusion rate is increasing steadily.

The interim analysis has been performed as scheduled and the DSMB decided that nothing should be changed.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Acute Respiratory Failure
Intervention  ICMJE
  • Procedure: standard oxygen

    Devices used to treat spontaneously ventilating patients in the ICU who require supplemental oxygen. They deliver either

    • low-flow oxygen [including nasal cannula, Ventimask® without Venturi effect, and non-rebreather mask]
    • or medium-flow oxygen [Venturi masks and medium-flow facemasks]
  • Procedure: HFNO
    The intervention is the use of a device that allows to deliver high flow humidified and warmed oxygen. The device used is the Optiflow™ (Fisher&Paykel, Courtaboeuf, France).
Study Arms  ICMJE
  • Active Comparator: standard oxygen group
    Oxygen therapy will be delivered using any device or combination of devices that are part of usual care: nasal oxygen, and mask with or without a reservoir bag and with or without the Venturi system
    Intervention: Procedure: standard oxygen
  • Experimental: High-flow nasal oxygen (HFNO) group

    Device that delivers humidified and warmed high-flow oxygen at flows greater than 15 L/min.

    HFNO will be initiated at a flow rate of 50 L/min and 100% FiO2. If the target SpO2 is not reached, the flow rate will be increased to 60 L/min. Then, FiO2 will be tapered to target an SpO2≥95. The minimal flow rate will be 45 L/min

    Intervention: Procedure: HFNO
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 20, 2018)
776
Original Estimated Enrollment  ICMJE
 (submitted: April 11, 2016)
778
Actual Study Completion Date  ICMJE December 31, 2017
Actual Primary Completion Date December 31, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Known immunosuppression defined as one or more of the following: (a) immunosuppressive drug or long-term [>3 months] or high-dose [>0.5 mg/kg/day] steroids; (b) solid organ transplantation; (c) solid tumour; (d) haematological malignancy.
  • ICU admission for any reason
  • Need for oxygen therapy ≥6 Liters/min defined as one or more of the following: (a) respiratory distress with a respiratory rate >30/min; (b) cyanosis; (c) laboured breathing; (d) SpO2<90%; and (e) expected respiratory deterioration during a procedure
  • Written informed consent from the patient or proxy (if present) before inclusion or once possible when patient has been included in a context of emergency.

Exclusion Criteria:

  • Patient admitted to the ICU for end-of-life care. Do-not-intubate (DNI) patients can be included.
  • Refusal of study participation or to pursue the study by the patient
  • Hypercapnia with a formal indication for NIV [PaCO2 ≥ 50 mmHg, formal indication for NIV]
  • Isolated cardiogenic pulmonary oedema [formal indication for NIV]. Patients with pulmonary oedema associated with another ARF etiology can be included.
  • Pregnancy or breastfeeding
  • Anatomical factors precluding the use of a nasal cannula
  • Absence of coverage by the French statutory healthcare insurance system
  • Post surgical setting from D1 to D6

After discussion at the investigator meeting and based on comments from the Data and Safety Monitoring Board on May 12, 2016, as all included patients need to have an acute hypoxemic respiratory failure and at least 6l of oxygen per minute, patients admitted to the ICU to secure any procedure (bronchoscopy etc..) or those not admitted for acute respiratory failure and who undergo intubation, will NOT be included in this trial. Only patients meeting criteria of acute respiratory failure will be included in this trial.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02739451
Other Study ID Numbers  ICMJE AOM15003
P150912 ( Other Identifier: Assistance Publique Hopitaux de Paris )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Assistance Publique - Hôpitaux de Paris
Study Sponsor  ICMJE Assistance Publique - Hôpitaux de Paris
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Elie Azoulay, MDPhD APHP
PRS Account Assistance Publique - Hôpitaux de Paris
Verification Date July 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP