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

Primary Purpose

Acute Respiratory Failure

Status

Completed

Phase

Not Applicable

Locations

France

Study Type

Interventional

Intervention

standard oxygen

HFNO

About this trial

This is an interventional treatment trial for Acute Respiratory Failure focused on measuring immunocompromized patients, critically ill patients

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Medical ICU

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

standard oxygen group

High-flow nasal oxygen (HFNO) group

Arm Description

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

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

Outcomes

Primary Outcome Measures

All-cause day-28 mortality

Secondary Outcome Measures

Intubation or reintubation rate

proportion of patients requiring invasive mechanical ventilation

patient comfort

Visual Analogue Scale (VAS) score

Intensity of dyspnoea

Visual Analogue Scale (VAS) score

Perceived Exertion

Borg scale

Respiratory rate

Oxygenation

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

Incidence of ICU-acquired infections

Time to clear pulmonary infiltrates

Murray score

Oxygen-free and ventilation-free survivals

Re-intubation rate

Lowest median SpO2 during intubation

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

Hypoxemic cardiac arrests

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

Full Information

NCT ID

NCT02739451

First Posted

March 29, 2016

Last Updated

July 20, 2018

Sponsor

Assistance Publique - Hôpitaux de Paris

1. Study Identification

Unique Protocol Identification Number

NCT02739451

Brief Title

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

Acronym

HIGH

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

July 2018

Overall Recruitment Status

Completed

Study Start Date

May 2016 (undefined)

Primary Completion Date

December 31, 2017 (Actual)

Study Completion Date

December 31, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Assistance Publique - Hôpitaux de Paris

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Acute Respiratory Failure

Keywords

immunocompromized patients, critically ill patients

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

776 (Actual)

8. Arms, Groups, and Interventions

Arm Title

standard oxygen group

Arm Type

Active Comparator

Arm Description

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

Arm Title

High-flow nasal oxygen (HFNO) group

Arm Type

Experimental

Arm Description

Intervention Type

Procedure

Intervention Name(s)

standard oxygen

Intervention Description

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]

Intervention Type

Procedure

Intervention Name(s)

HFNO

Intervention Description

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).

Primary Outcome Measure Information:

Title

All-cause day-28 mortality

Time Frame

28 days

Secondary Outcome Measure Information:

Title

Intubation or reintubation rate

Description

proportion of patients requiring invasive mechanical ventilation

Time Frame

days 3 and 28

Title

patient comfort

Description

Visual Analogue Scale (VAS) score

Time Frame

28 days

Title

Intensity of dyspnoea

Description

Visual Analogue Scale (VAS) score

Time Frame

days 1-3

Title

Perceived Exertion

Description

Borg scale

Time Frame

days 1-3

Title

Respiratory rate

Time Frame

days 1-3

Title

Oxygenation

Description

based on continuous saturation of peripheral oxygen (SpO2) monitoring, lowest SpO2 from D1 to D3 and PaO2/FiO2 on D1, D2, and D3

Time Frame

days 1-3

Title

ICU length of stay

Time Frame

28 days

Title

Incidence of ICU-acquired infections

Time Frame

28 days

Title

Time to clear pulmonary infiltrates

Description

Murray score

Time Frame

28 days

Title

Oxygen-free and ventilation-free survivals

Time Frame

day 28

Title

Re-intubation rate

Time Frame

day 28

Title

Lowest median SpO2 during intubation

Description

for patients who were intubated during the study period

Time Frame

days 1-3

Title

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

Title

Hypoxemic cardiac arrests

Description

Time Frame

day 28

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Elie Azoulay, MDPhD

Organizational Affiliation

APHP

Official's Role

Principal Investigator

Facility Information:

Facility Name

Medical ICU

City

Paris

ZIP/Postal Code

75010

Country

France

12. IPD Sharing Statement

Plan to Share IPD

Undecided

Citations:

PubMed Identifier

30357270

Citation

Azoulay E, Lemiale V, Mokart D, Nseir S, Argaud L, Pene F, Kontar L, Bruneel F, Klouche K, Barbier F, Reignier J, Berrahil-Meksen L, Louis G, Constantin JM, Mayaux J, Wallet F, Kouatchet A, Peigne V, Theodose I, Perez P, Girault C, Jaber S, Oziel J, Nyunga M, Terzi N, Bouadma L, Lebert C, Lautrette A, Bige N, Raphalen JH, Papazian L, Darmon M, Chevret S, Demoule A. Effect of High-Flow Nasal Oxygen vs Standard Oxygen on 28-Day Mortality in Immunocompromised Patients With Acute Respiratory Failure: The HIGH Randomized Clinical Trial. JAMA. 2018 Nov 27;320(20):2099-2107. doi: 10.1001/jama.2018.14282.

Results Reference

derived

PubMed Identifier

29506579

Citation

Azoulay E, Lemiale V, Mokart D, Nseir S, Argaud L, Pene F, Kontar L, Bruneel F, Klouche K, Barbier F, Reignier J, Stoclin A, Louis G, Constantin JM, Mayaux J, Wallet F, Kouatchet A, Peigne V, Perez P, Girault C, Jaber S, Oziel J, Nyunga M, Terzi N, Bouadma L, Lebert C, Lautrette A, Bige N, Raphalen JH, Papazian L, Rabbat A, Darmon M, Chevret S, Demoule A. High-flow nasal oxygen vs. standard oxygen therapy in immunocompromised patients with acute respiratory failure: study protocol for a randomized controlled trial. Trials. 2018 Mar 5;19(1):157. doi: 10.1186/s13063-018-2492-z.

Results Reference

derived

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

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