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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)

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ClinicalTrials.gov Identifier: NCT03406572
Recruitment Status : Recruiting
First Posted : January 23, 2018
Last Update Posted : May 28, 2018
Sponsor:
Collaborator:
Direction Générale de l'Offre de Soins
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

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.


Condition or disease Intervention/treatment Phase
Hypercapnic Respiratory Failure Device: HFHO Group Device: Standard O2 Not Applicable

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

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 242 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Supportive Care
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
Actual Study Start Date : May 18, 2018
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : July 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: HFHO Group
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.
Device: HFHO Group
  • Common name: humidifier with integrated flow generator that delivers high flow warmed and humidified respiratory gases
  • Brand name: Airvo 2
Other Name: High-flow heated and humidified nasal oxygen therapy (HFHO).

Active Comparator: Standard O2 Group
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
Device: Standard O2
Standard oxygen therapy




Primary Outcome Measures :
  1. Number of ventilator-free days (VFDs) alive [ Time Frame: At day 28 after study enrollment ]

Secondary Outcome Measures :
  1. Delay of completion of stopping rules for NIV [ Time Frame: 28 days post-randomisation ]
  2. 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 ]
  3. 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 ]
  4. Hospital length of stay [ Time Frame: 28 days post-randomisation ]
  5. All cause mortality [ Time Frame: 28 days post-randomisation ]
  6. 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 ]
  7. Number of NIV sessions [ Time Frame: 28 days post-randomisation ]
  8. Duration of NIV sessions (hours) [ Time Frame: 28 days post-randomisation ]
  9. 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 ]
  10. 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 ]
  11. Proportion of patients achieving 48 consecutive hours of unassisted breathing [ Time Frame: 28 days post-randomisation ]
  12. Proportion of patients requiring NIV resumption after 48 consecutive hours of unassisted breathing [ Time Frame: 28 days post-randomisation ]
  13. 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 ]
  14. 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 ]
  15. 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 ]
  16. 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 ]
  17. 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 ]
  18. 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 ]
  19. 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 ]
  20. Respiratory rate during NIV periods [ Time Frame: after 1 hour of NIV, up to 28 days ]
  21. Proportion of patients using accessory muscles during NIV periods [ Time Frame: after 1 hour of NIV, up to 28 days ]
  22. 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 ]
  23. 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 ]
  24. Proportion of patients refusing to resume NIV (despite meeting criteria) [ Time Frame: 28 days post-randomisation ]
  25. Proportion of patients who need secondary intubation and IMV [ Time Frame: 28 days post-randomisation ]
  26. 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 ]
  27. 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 ]
  28. 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 ]
  29. 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 ]
  30. 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 ]
  31. 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 ]
  32. 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 ]
  33. 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 ]
  34. 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 ]
  35. 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 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria :

  • Adult patients aged 18 or above admitted to an ICU, an intermediate care, or a respiratory care unit;
  • Chronic respiratory failure known (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 non-invasive ventilation 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;
  • Pure restrictive lung disease (thoracic deformity, neuro-muscular pathology) and pure obstructive sleep apnoea
  • Immediate need for intubation (including respiratory or cardiac arrest);
  • Persistent hemodynamic instability (use of vasopressors for > 1 hour);
  • Multiple organ failure (score SOFA>6) ;
  • NIV treatment for >1 hour before admission to ICU, intermediate care, or respiratory care unit ;
  • Anticipated difficulties to conduct NIV (facial trauma or deformation, edentulous patient);
  • End stage chronic respiratory insufficiency (defined as use of NIV at home);
  • Non-treated pneumothorax;
  • Impossibility to perform subjective assessment of dyspnea and comfort (cognitive impairment);
  • Refusal to participate;
  • Pregnancy/breastfeeding;
  • Patient under guardianship or trusteeship;
  • Current participation in another clinical trial with an endpoint related to NIV.
  • No affiliation to social security (beneficiary 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03406572


Contacts
Contact: Jean-Damien Ricard 01.47.60.61.95 ext +33 jean-damien.ricard@aphp.fr

Locations
France
Service de Réanimation Médico-Chirurgicale, Hôpital Louis Mourier Recruiting
Colombes, France, 92700
Contact: Jean-Damien Ricard, MD-PhD    01.47.60.61.95 ext +33    jean-damien.ricard@aphp.fr   
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Direction Générale de l'Offre de Soins
Investigators
Principal Investigator: Jean-Damien Ricard Assistance Publique - Hôpitaux de Paris

Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT03406572     History of Changes
Other Study ID Numbers: K160911J
First Posted: January 23, 2018    Key Record Dates
Last Update Posted: May 28, 2018
Last Verified: November 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Assistance Publique - Hôpitaux de Paris:
Acute on chronic respiratory failure
High-Flow heated and humidified nasal oxygen therapy

Additional relevant MeSH terms:
Respiratory Insufficiency
Hypercapnia
Respiration Disorders
Respiratory Tract Diseases
Signs and Symptoms, Respiratory
Signs and Symptoms