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Use of Nasal High Flow Oxygen During Breaks of Non-invasive Ventilation for Patients With Hypercapnic Respiratory Failure (HIGH FLOW ACRF)

Primary Purpose

Hypercapnic Respiratory Failure

Status
Completed
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
HFHO Group
Standard O2
Sponsored by
Assistance Publique - Hôpitaux de Paris
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional supportive care trial for Hypercapnic Respiratory Failure focused on measuring Acute on chronic respiratory failure, High-Flow heated and humidified nasal oxygen therapy

Eligibility Criteria

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

Inclusion criteria

  • Adult patients aged 18 or above, admitted to an ICU, an intermediate care or a respiratory care unit;
  • Chronic respiratory disease previously documented or strongly suspected on clinical, radiological and blood gazes data and pulmonary function tests, in connection with an obstructive respiratory disease (COPD, emphysema, overlap-syndrome (COPD + obstructive sleep apnoea) or mixed (bronchiectasis, obesity-hypoventilation syndrome))
  • Patients requiring NIV for hypercapnic ARF (whatever the precipitating cause) i.e. with clinical signs of moderate to severe respiratory distress : dyspnea and /or respiratory rate > 25/min and/or use of accessory respiratory muscles and/or paradoxical abdominal motion and/or signs of respiratory encephalopathy (sleepiness, asterixis, confusion); and respiratory acidosis on arterial blood gases, defined by pH<7.35 and PaCO2 > 45 mmHg despite the careful supply of oxygen and appropriate therapy that may include bronchodilators, corticosteroids and antibiotics

Exclusion criteria

  • Contraindications to NIV;
  • Purely restrictive lung disease (thoracic deformity, neuro-muscular pathology) and pure obstructive sleep apnoea (without spirometric disturbance or daytime gas anomaly)
  • Immediate need for intubation (respiratory or cardiac arrest);
  • Persistent hemodynamic instability (use of vasopressors for > 1 hour);
  • Multiple organ failure (score SOFA>6);
  • NIV treatement for >3 consecutive hours before admission to ICU, intermediate care, or respiratory care unit and before randomization;
  • Anticipated difficulties to conduct NIV (facial trauma or deformation, edentulous patient);
  • End stage chronic respiratory insufficiency (defined as use of NIV at home or CPAP treatment at home);
  • Long-term use of NIV or CPAP (defined as use of NIV or CPAP treatment at home)
  • Non-treated pneumothorax;
  • Impossibility to perform subjective assessment of dyspnea and comfort (cognitive impairment);
  • Patient under guardianship or trusteeship;
  • Pregnancy/breastfeeding;
  • Decision to withhold or to withdraw life-sustaining treatments (including intubation)
  • Moribund state
  • Current participation in another clinical trial with an endpoint related to NIV.
  • No affiliation to social security (beneficial or assignee);
  • Lack of oral informed consent (express consent) from the patient or relative of appropriate. For those patients that are unable to give written informed consent at the time of enrollment due to the severity of their illness, a process of delayed consent will be used.

Sites / Locations

  • Service de Réanimation Médico-Chirurgicale, Hôpital Louis Mourier

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

HFHO Group

Standard O2 Group

Arm Description

Patients will receive a first NIV session (for 2 hours) with predefined parameters, and ABG will be performed between one and two hours of starting NIV. NIV will be extended according to ABG result (i.e. extended if pH < 7.30). Switch from NIV to oxygen will require predefined criteria. In-between each NIV session, oxygen will be delivered using a high flow nasal cannula, with a flow of 50-60L/min and a FiO2 set to reach a targeted SpO2: 88%≤SpO2 ≤ 92%. Predefined criteria will be used to resume NIV.

NIV will be initiated based on the same criteria and with the same parameters as the HFHO group. ABG will also be performed between one and two hours and NIV extended according to ABG result (i.e. extended if pH < 7.30). Switch from NIV to oxygen will require the same predefined criteria as the HFHO group. In-between each NIV session, oxygen will be delivered using standard low flow O2 to reach the same targeted SpO2: 88% ≤SpO2 ≤ 92%. Similar criteria will be used to resume NIV

Outcomes

Primary Outcome Measures

Number of ventilator-free days (VFDs) alive

Secondary Outcome Measures

Delay of completion of stopping rules for NIV
Patient self-assessement of comfort during each SB period measured by Visual Analog Scale (score range 0-10, higher values represent a better outcome)
Nurse assessement of comfort during each SB period measured by Likert scale (score range1-5; higher values represent a better outcome)
Hospital length of stay
All cause mortality
Proportion of patients with facial skin erythema and/or ulceration
Number of NIV sessions
Duration of NIV sessions (hours)
Number of days between the day the patient first meets criteria for NIV cessation and day 28 post-randomization
Number of days between the day of initially achieving unassisted ventilation and day 28 post-randomization (i.e. after having successfully spent 48 consecutive hours of unassisted breathing)
Proportion of patients achieving 48 consecutive hours of daytime unassisted breathing
Proportion of patients requiring NIV resumption after 48 consecutive hours of daytime unassisted breathing
Patient self-assessement of comfort during each NIV period measured by Visual Analog Scale (score range 0-10, higher values represent a better outcome)
Nurse assessement of comfort during each NIV period measured by Likert scale (score range1-5; higher values represent a better outcome)
Patient self-assessement of dyspnea during each SB period measured by Visual Analog Scale (range 0-10; higher values represent a worst outcome)
Nurse assessement of dyspnea during each SB period measured by Likert scale (score range1-5; higher values represent a worst outcome)
Patient self-assessement of dyspnea during each NIV period measured by Visual Analog Scale (range 0-10; higher values represent a worst outcome)
Nurse assessement of dyspnea during each NIV period measured by Likert scale (score range1-5; higher values represent a worst outcome)
Respiratory rate during SB periods
Respiratory rate during NIV periods
Proportion of patients using accessory muscles during NIV periods
Daily arterial blood gases (ABG) (in terms of pH, PaCO2 and PaO2 measured between 8-10 am).
Proportion of patients with premature NIV cessation (intolerance) (defined by agitation and/or mask removal, and/or patient's wish to interrupt session before)
Proportion of patients refusing to resume NIV (despite meeting criteria)
Proportion of patients who need secondary intubation and IMV
Proportion of patients with nasal bridge ulceration
Proportion of patients with eye irritation
Proportion of patients with nasal congestion
Proportion of patients with nasal/oral dryness
Proportion of patients with gastric distension
Proportion of patients with nosocomial pneumonia
Proportion of patients with pneumothorax
Proportion of patients with arterial hypotension
Proportion of patients with nostril ulceration (including nasolabial angle, columella, nostril sill)
Proportion of patients with nose bleeding

Full Information

First Posted
November 23, 2017
Last Updated
September 4, 2023
Sponsor
Assistance Publique - Hôpitaux de Paris
Collaborators
Direction Générale de l'Offre de Soins
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1. Study Identification

Unique Protocol Identification Number
NCT03406572
Brief Title
Use of Nasal High Flow Oxygen During Breaks of Non-invasive Ventilation for Patients With Hypercapnic Respiratory Failure
Acronym
HIGH FLOW ACRF
Official Title
Comparison of High Flow Nasal Cannula Oxygen and Conventional Oxygen Therapy on Ventilatory Support Duration During Acute-on-chronic Respiratory Failure: a Multicenter, Randomized, Controlled Trial
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Completed
Study Start Date
May 18, 2018 (Actual)
Primary Completion Date
June 18, 2023 (Actual)
Study Completion Date
August 18, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Assistance Publique - Hôpitaux de Paris
Collaborators
Direction Générale de l'Offre de Soins

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
Chronic respiratory insufficiency and COPD are the third leading cause of death worldwide. Patients decompensate at various stages of their disease and exhibit acute-on-chronic respiratory failure (ACRF), a frequent cause of ICU hospitalization for hypercapnic acute respiratory failure (ARF). Non-invasive ventilation (NIV) is the first line ventilatory treatment for hypercapnic ARF. It is applied intermittently, separated by periods of spontaneous breathing (SB) with standard oxygen (O2). Standard O2 has drawbacks that limit the benefit of intermittent NIV in hypercapnic ARF: limited gas flow which is well below the patient's inspiratory flow rate, limited capacity and efficiency of oxygenation with non-controlled FiO2 (risk of excessive oxygen and induced hypercapnia), and cold and dry gas leading to discomfort and under-humidification of the airways and tracheobronchial secretions. Benefits in terms of work of breathing and CO2 removal resulting from PEEP and pressure support applied during NIV periods could be rapidly lost during standard O2. Recently, use of high-flow heated and humidified nasal oxygen therapy (HFHO) has gained enthusiasm among intensivists to manage ARF. HFHO delivers high flows (up to 60L/min, that generate moderate PEEP) of heated and humidified oxygen at a controlled and adjustable FiO2 (21 to 100%) that rapidly improve respiratory distress symptoms, oxygenation, respiratory comfort and outcome of patients with hypoxemic ARF. These unique features of HFHO could overcome some of the drawbacks of standard O2 during SB periods in hypercapnic ARF. Indeed, PEEP effect, washout of nasopharyngeal dead-space limiting CO2 re-breathing and inspired gas conditioning preserving adequate mucosal function and secretion removal, could potentially contribute to decrease airways resistance, intrinsic PEEP and work of breathing, while improving patient comfort. Investigators aim to determine if the use of HFHO, as compared to standard O2, increases the number of ventilator-free days (VFDs) and alive at day 28 in patients with hypercapnic ARF admitted in an ICU, an intermediate care, or a respiratory care unit, and requiring NIV.
Detailed Description
In both groups, treatment will start with a first NIV session of 2 hours, with arterial blood gas measurement between one hour and two hours after initiating the NIV session. The NIV will be extended for those patients with a pH < 7.30. In both groups, patients will be assessed for their tolerance of NIV and their ability to switch to spontaneous breathing every hour +/- 30 min, except during sleep (10 pm-8 am); they will be assessed for their tolerance of spontaneous breathing and for the need of resumption of NIV every 2 hours+/- 30 min and every 4 +/- 1 hours thereafter. To ensure the consistency of indications of NIV and invasive mechanical ventilation (IMV) across centers and reduce potential bias, NIV and IMV will be initiated and stopped in the same way in the two groups, using predefined criteria. Inclusion (day 0): informed consent, randomisation (HFHO group/standard O2 group), NIV initiation (for 2 hours), clinical and paraclinical exam including ABG, data collection Follow-up (day 1 to day 28) : NIV, clinical exam, ABG, data collection

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypercapnic Respiratory Failure
Keywords
Acute on chronic respiratory failure, High-Flow heated and humidified nasal oxygen therapy

7. Study Design

Primary Purpose
Supportive Care
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
161 (Actual)

8. Arms, Groups, and Interventions

Arm Title
HFHO Group
Arm Type
Experimental
Arm Description
Patients will receive a first NIV session (for 2 hours) with predefined parameters, and ABG will be performed between one and two hours of starting NIV. NIV will be extended according to ABG result (i.e. extended if pH < 7.30). Switch from NIV to oxygen will require predefined criteria. In-between each NIV session, oxygen will be delivered using a high flow nasal cannula, with a flow of 50-60L/min and a FiO2 set to reach a targeted SpO2: 88%≤SpO2 ≤ 92%. Predefined criteria will be used to resume NIV.
Arm Title
Standard O2 Group
Arm Type
Active Comparator
Arm Description
NIV will be initiated based on the same criteria and with the same parameters as the HFHO group. ABG will also be performed between one and two hours and NIV extended according to ABG result (i.e. extended if pH < 7.30). Switch from NIV to oxygen will require the same predefined criteria as the HFHO group. In-between each NIV session, oxygen will be delivered using standard low flow O2 to reach the same targeted SpO2: 88% ≤SpO2 ≤ 92%. Similar criteria will be used to resume NIV
Intervention Type
Device
Intervention Name(s)
HFHO Group
Other Intervention Name(s)
High-flow heated and humidified nasal oxygen therapy (HFHO).
Intervention Description
Common name: humidifier with integrated flow generator that delivers high flow warmed and humidified respiratory gases Brand name: Airvo 2
Intervention Type
Device
Intervention Name(s)
Standard O2
Intervention Description
Standard oxygen therapy
Primary Outcome Measure Information:
Title
Number of ventilator-free days (VFDs) alive
Time Frame
At day 28 after study enrollment
Secondary Outcome Measure Information:
Title
Delay of completion of stopping rules for NIV
Time Frame
28 days post-randomisation
Title
Patient self-assessement of comfort during each SB period measured by Visual Analog Scale (score range 0-10, higher values represent a better outcome)
Time Frame
After 2 hours of SB in the 48 first hours, and every 4 hours thereafter, up to 28 days
Title
Nurse assessement of comfort during each SB period measured by Likert scale (score range1-5; higher values represent a better outcome)
Time Frame
After 2 hours of SB in the 48 first hours, and every 4 hours thereafter, up to 28 days
Title
Hospital length of stay
Time Frame
28 days post-randomisation
Title
All cause mortality
Time Frame
28 days post-randomisation
Title
Proportion of patients with facial skin erythema and/or ulceration
Time Frame
After 2 hours of SB in the 48 first hours, and every 4 hours thereafter; and after 1 hour of NIV; up to 28 days
Title
Number of NIV sessions
Time Frame
28 days post-randomisation
Title
Duration of NIV sessions (hours)
Time Frame
28 days post-randomisation
Title
Number of days between the day the patient first meets criteria for NIV cessation and day 28 post-randomization
Time Frame
28 days post-randomisation
Title
Number of days between the day of initially achieving unassisted ventilation and day 28 post-randomization (i.e. after having successfully spent 48 consecutive hours of unassisted breathing)
Time Frame
28 days post-randomisation
Title
Proportion of patients achieving 48 consecutive hours of daytime unassisted breathing
Time Frame
28 days post-randomisation
Title
Proportion of patients requiring NIV resumption after 48 consecutive hours of daytime unassisted breathing
Time Frame
28 days post-randomisation
Title
Patient self-assessement of comfort during each NIV period measured by Visual Analog Scale (score range 0-10, higher values represent a better outcome)
Time Frame
after 1 hour of NIV, up to 28 days
Title
Nurse assessement of comfort during each NIV period measured by Likert scale (score range1-5; higher values represent a better outcome)
Time Frame
after 1 hour of NIV, up to 28 days
Title
Patient self-assessement of dyspnea during each SB period measured by Visual Analog Scale (range 0-10; higher values represent a worst outcome)
Time Frame
after 2 hours of SB in the 48 first hours, and every 4 hours thereafter, up to 28 days
Title
Nurse assessement of dyspnea during each SB period measured by Likert scale (score range1-5; higher values represent a worst outcome)
Time Frame
after 2 hours of SB in the 48 first hours, and every 4 hours thereafter, up to 28 days
Title
Patient self-assessement of dyspnea during each NIV period measured by Visual Analog Scale (range 0-10; higher values represent a worst outcome)
Time Frame
after 1 hour of NIV, up to 28 days
Title
Nurse assessement of dyspnea during each NIV period measured by Likert scale (score range1-5; higher values represent a worst outcome)
Time Frame
after 1 hour of NIV, up to 28 days
Title
Respiratory rate during SB periods
Time Frame
after 2 hours of SB in the 48 first hours, and every 4 hours thereafter, up to 28 days
Title
Respiratory rate during NIV periods
Time Frame
after 1 hour of NIV, up to 28 days
Title
Proportion of patients using accessory muscles during NIV periods
Time Frame
after 1 hour of NIV, up to 28 days
Title
Daily arterial blood gases (ABG) (in terms of pH, PaCO2 and PaO2 measured between 8-10 am).
Time Frame
up to 28 days post-randomisation
Title
Proportion of patients with premature NIV cessation (intolerance) (defined by agitation and/or mask removal, and/or patient's wish to interrupt session before)
Time Frame
28 days post-randomisation
Title
Proportion of patients refusing to resume NIV (despite meeting criteria)
Time Frame
28 days post-randomisation
Title
Proportion of patients who need secondary intubation and IMV
Time Frame
28 days post-randomisation
Title
Proportion of patients with nasal bridge ulceration
Time Frame
After 2 hours of SB in the 48 first hours, and every 4 hours thereafter; and after 1 hour of NIV; up to 28 days
Title
Proportion of patients with eye irritation
Time Frame
After 2 hours of SB in the 48 first hours, and every 4 hours thereafter; and after 1 hour of NIV; up to 28 days
Title
Proportion of patients with nasal congestion
Time Frame
After 2 hours of SB in the 48 first hours, and every 4 hours thereafter; and after 1 hour of NIV; up to 28 days
Title
Proportion of patients with nasal/oral dryness
Time Frame
After 2 hours of SB in the 48 first hours, and every 4 hours thereafter; and after 1 hour of NIV; up to 28 days
Title
Proportion of patients with gastric distension
Time Frame
After 2 hours of SB in the 48 first hours, and every 4 hours thereafter; and after 1 hour of NIV; up to 28 days
Title
Proportion of patients with nosocomial pneumonia
Time Frame
After 2 hours of SB in the 48 first hours, and every 4 hours thereafter; and after 1 hour of NIV; up to 28 days
Title
Proportion of patients with pneumothorax
Time Frame
After 2 hours of SB in the 48 first hours, and every 4 hours thereafter; and after 1 hour of NIV; up to 28 days
Title
Proportion of patients with arterial hypotension
Time Frame
After 2 hours of SB in the 48 first hours, and every 4 hours thereafter; and after 1 hour of NIV; up to 28 days
Title
Proportion of patients with nostril ulceration (including nasolabial angle, columella, nostril sill)
Time Frame
After 2 hours of SB in the 48 first hours, and every 4 hours thereafter; and after 1 hour of NIV; up to 28 days
Title
Proportion of patients with nose bleeding
Time Frame
After 2 hours of SB in the 48 first hours, and every 4 hours thereafter; and after 1 hour of NIV; up to 28 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria Adult patients aged 18 or above, admitted to an ICU, an intermediate care or a respiratory care unit; Chronic respiratory disease previously documented or strongly suspected on clinical, radiological and blood gazes data and pulmonary function tests, in connection with an obstructive respiratory disease (COPD, emphysema, overlap-syndrome (COPD + obstructive sleep apnoea) or mixed (bronchiectasis, obesity-hypoventilation syndrome)) Patients requiring NIV for hypercapnic ARF (whatever the precipitating cause) i.e. with clinical signs of moderate to severe respiratory distress : dyspnea and /or respiratory rate > 25/min and/or use of accessory respiratory muscles and/or paradoxical abdominal motion and/or signs of respiratory encephalopathy (sleepiness, asterixis, confusion); and respiratory acidosis on arterial blood gases, defined by pH<7.35 and PaCO2 > 45 mmHg despite the careful supply of oxygen and appropriate therapy that may include bronchodilators, corticosteroids and antibiotics Exclusion criteria Contraindications to NIV; Purely restrictive lung disease (thoracic deformity, neuro-muscular pathology) and pure obstructive sleep apnoea (without spirometric disturbance or daytime gas anomaly) Immediate need for intubation (respiratory or cardiac arrest); Persistent hemodynamic instability (use of vasopressors for > 1 hour); Multiple organ failure (score SOFA>6); NIV treatement for >3 consecutive hours (without any interruption) before admission to ICU, intermediate care, or respiratory care unit and before randomization; Anticipated difficulties to conduct NIV (facial trauma or deformation, edentulous patient); End stage chronic respiratory insufficiency (defined as use of NIV at home or CPAP treatment at home and life expectancy below 6 month); Non-treated pneumothorax; Impossibility to perform subjective assessment of dyspnea and comfort (cognitive impairment); Patient under guardianship or trusteeship; Pregnancy/breastfeeding; Decision to withhold or to withdraw life-sustaining treatments (including intubation) Moribund state Current participation in another clinical trial with an endpoint related to NIV. No affiliation to social security (beneficial or assignee); Refusal to participate to the study (patient or legal representative or family member or close relative if present
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jean-Damien Ricard
Organizational Affiliation
Assistance Publique - Hôpitaux de Paris
Official's Role
Principal Investigator
Facility Information:
Facility Name
Service de Réanimation Médico-Chirurgicale, Hôpital Louis Mourier
City
Colombes
ZIP/Postal Code
92700
Country
France

12. IPD Sharing Statement

Plan to Share IPD
Undecided
Citations:
PubMed Identifier
30232113
Citation
Ricard JD, Dib F, Esposito-Farese M, Messika J, Girault C; REVA network. Comparison of high flow nasal cannula oxygen and conventional oxygen therapy on ventilatory support duration during acute-on-chronic respiratory failure: study protocol of a multicentre, randomised, controlled trial. The 'HIGH-FLOW ACRF' study. BMJ Open. 2018 Sep 19;8(9):e022983. doi: 10.1136/bmjopen-2018-022983.
Results Reference
derived

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Use of Nasal High Flow Oxygen During Breaks of Non-invasive Ventilation for Patients With Hypercapnic Respiratory Failure

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