Acute Respiratory FailureHIGHNCT02739451
A Randomised Controlled Trial of High-Flow Nasal Oxygen Versus Standard Oxygen Therapy in Critically Ill Immunocompromised Patients
A study testing standard oxygen and HFNO in people with Acute Respiratory Failure, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial 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%. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Respiratory Failure
- What is being tested?
- standard oxygen and HFNO
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 776 participants
- Where
- 1 siteFrance
- Study dates
- May 2016to 31 Dec 2017
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read more
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
Read the 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.
- Conditions
- Acute Respiratory Failure
- Being tested
- standard oxygen, HFNO
- Keywords
- immunocompromized patients, critically ill patients
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
standard oxygenProcedure or surgery
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]
HFNOProcedure or surgery
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 group | Role | What they receive |
|---|---|---|
| standard oxygen group | Active comparator | 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 Receives: Procedure: standard oxygen |
| High-flow nasal oxygen (HFNO) group | Experimental | 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 Receives: Procedure: HFNO |
What is being measured
The primary outcome is the main question the study is designed to answer.
All-cause day-28 mortality
Measured: 28 days
Secondary outcomes (14)
Intubation or reintubation rate
proportion of patients requiring invasive mechanical ventilation
Measured: days 3 and 28
patient comfort
Visual Analogue Scale (VAS) score
Measured: 28 days
Intensity of dyspnoea
Visual Analogue Scale (VAS) score
Measured: days 1-3
Perceived Exertion
Borg scale
Measured: days 1-3
Respiratory rate
Measured: days 1-3
Oxygenation
based on continuous saturation of peripheral oxygen (SpO2) monitoring, lowest SpO2 from D1 to D3 and PaO2/FiO2 on D1, D2, and D3
Measured: days 1-3
ICU length of stay
Measured: 28 days
Incidence of ICU-acquired infections
Measured: 28 days
Time to clear pulmonary infiltrates
Murray score
Measured: 28 days
Oxygen-free and ventilation-free survivals
Measured: day 28
Re-intubation rate
Measured: day 28
Lowest median SpO2 during intubation
for patients who were intubated during the study period
Measured: days 1-3
Repartition of acute mild/moderate/severe respiratory distress syndrome (ARDS) stages after intubation or reintubation as defined by the Berlin definition
Measured: day 28
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
Measured: day 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Apr 2016 (estimated)
- Study startMay 2016
- Primary completion31 Dec 2017
- Study completion31 Dec 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Acute Respiratory FailureStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 776 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Elie Azoulay, MDPhD, Principal investigator, APHP
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02739451
- Sponsor's protocol ID
- AOM15003
- Other IDs
- P150912
- Acronym
- HIGH
- Status last verified
- Jul 2018
- First submitted
- 29 Mar 2016
- Last updated
- 24 Jul 2018
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Publications
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.
PubMed 30357270Azoulay 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.
PubMed 29506579
Study at a glance
From the registry record, last updated by the sponsor on 24 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised Controlled Trial of High-Flow Nasal Oxygen Versus Standard Oxygen Therapy in Critically Ill Immunocompromised Patients
- ClinicalTrials.gov ID
- NCT02739451
- Acronym / sponsor ID
- HIGH / AOM15003
- Conditions
- Acute Respiratory Failure
- Keywords
- immunocompromized patients, critically ill patients
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 776 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- May 2016
- Primary completion
- 31 Dec 2017 (actual)
- Study completion
- 31 Dec 2017 (actual)
- First posted
- 15 Apr 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| standard oxygen group | Active comparator | Procedure: standard oxygenOxygen 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 |
| High-flow nasal oxygen (HFNO) group | Experimental | Procedure: HFNODevice 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| standard oxygenDevices 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 or surgery | standard oxygen group |
| HFNOThe 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). | Procedure or surgery | High-flow nasal oxygen (HFNO) group |
Primary outcome
All-cause day-28 mortality
Time frame: 28 days
14 secondary outcomes
Intubation or reintubation rate
Time frame: days 3 and 28
patient comfort
Time frame: 28 days
Intensity of dyspnoea
Time frame: days 1-3
Perceived Exertion
Time frame: days 1-3
Respiratory rate
Time frame: days 1-3
Oxygenation
Time frame: days 1-3
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
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
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jul 2018.
- Derived from this study: PubMed 30357270Azoulay 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.
- Derived from this study: PubMed 29506579Azoulay 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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Elie Azoulay, MDPhD principal investigator
APHP
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing standard oxygen and HFNO in people with Acute Respiratory Failure, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
All-cause day-28 mortality (time frame: 28 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02739451, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jul 2018.