High Flow Therapy for the Treatment of Respiratory Failure in the ED

Vapotherm High Flow Therapy for the Treatment of Respiratory Failure in the ED: A Randomized Controlled Trial

The overall objective of this study is to determine if Vapotherm high flow nasal cannula therapy (HFT), when used to treat respiratory failure in the ED, is at least equivalent to the current standard of care for non-invasive ventilatory support, non-invasive positive pressure mask ventilation (NIPPV). Moreover, this study will investigate the potential that HFT has possible advantages over NIPPV, such as decreased time to patient stability from respiratory failure, and the ease of use as a first line intervention for respiratory failure in the ED environment.

The hypothesis is that HFT via the Vapotherm Precision Flow will demonstrate clinical non-inferiority when compared to NIPPV with regard to treatment failure by way of an impact on ventilation indices and a lower intolerance rate, and have a positive association with hospital disposition and length of stay.

Study Overview

• Status: Completed
• Conditions: Acute Respiratory Failure
• Intervention / Treatment: Device: Noninvasive positive pressure ventilation (NIPPV); Device: Vapotherm

• Study Type: Interventional
• Enrollment (Actual): 204
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Athens, Georgia, United States, 30606
      • Athens Regional Medical Center
  • South Carolina
    • Florence, South Carolina, United States, 29506
      • McLeod Regional Medical Center
  • Tennessee
    • Chattanooga, Tennessee, United States, 37403
      • Erlanger Health System
  • Texas
    • Houston, Texas, United States, 77030
      • Memorial Hermann Hospital
    • The Woodlands, Texas, United States, 77380
      • Memorial Hermann The Woodlands

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult patients (> 18 yrs of age)
• Presentation with acute respiratory failure according to the following criteria:
• If any of these are present: Respiratory Rate >22 or labored; Suspected Acute Respiratory Acidosis, as defined as pH <7.32 on initial blood gas(either arterial or venous); Hypoxemia, as defined as Pulse Ox <92%;
• Clinical decision to escalate therapy to non-invasive ventilatory support, or to maintain non-invasive ventilatory support if delivered to the ED on such.

Exclusion Criteria:

• Suspected drug overdose
• Cardiovascular instability as demonstrated by hypotension relative to initial clinical presentation that requires immediate intervention
• End stage cancer
• Life expectancy < 6 months
• Respiratory arrest or significant respiratory depression on presentation
• Glasgow Coma Scale score < 9
• Cardiac arrest on initial presentation
• Need for emergent intubation
• Known or suspected cerebrovascular accident
• Known or suspected ST segment elevation myocardial infarction
• Patients with increased risk of pulmonary aspiration
• Agitation or uncooperativeness

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Noninvasive positive pressure ventilation; Patients will be fit with an oronasal mask using a fitting gauge that will be applied by a respiratory therapist or other clinician skilled in management of NIPPV. Initial pressures will be at low end of suggested range but can be increased as rapidly as necessary to alleviate respiratory distress. Targets should be to lower respiratory rate to the low 20s and achieve tidal volumes of 6-8 ml/kg ideal body weight. If patients find pressures uncomfortably high, they can be lowered as necessary by 1 to 2 cmH2O decrements to enhance tolerance. EPAP (PEEP) can also be adjusted upward as needed to reduce triggering effort (by counterbalancing auto-PEEP) or to improve oxygenation. FIO2 will be 1.0 initially to assure adequate oxygenation, but should be adjusted promptly to maintain an FIO2 of no greater than 0.6 with an EPAP (PEEP) of not more than 10 cm H2O to maintain a PaO2 > 88%.	Device: Noninvasive positive pressure ventilation (NIPPV); Patients will be fit with an oronasal mask using a fitting gauge that will be applied by a respiratory therapist or other clinician skilled in management of NIPPV. Initial pressures will be at low end of suggested range but can be increased as rapidly as necessary to alleviate respiratory distress. Targets should be to lower respiratory rate to the low 20s and achieve tidal volumes of 6-8 ml/kg ideal body weight. If patients find pressures uncomfortably high, they can be lowered as necessary by 1 to 2 cmH2O decrements to enhance tolerance. EPAP (PEEP) can also be adjusted upward as needed to reduce triggering effort (by counterbalancing auto-PEEP) or to improve oxygenation. FIO2 will be 1.0 initially to assure adequate oxygenation, but should be adjusted promptly to maintain an FIO2 of no greater than 0.6 with an EPAP (PEEP) of not more than 10 cm H2O to maintain a PaO2 > 88%.; Other Names: BIPAP
Experimental: High flow therapy; Patients will be fit with a Vapotherm adult nasal cannula that will be applied by a respiratory therapist or other clinician skilled in management of HFT. Initial flow will be set to 35 L/min but can be decreased or increased as rapidly as necessary to alleviate respiratory distress and optimize patient comfort. Targets should be to lower respiratory rate to the low 20s and with a HFT flow rate between 20 to 35 L/min. Starting temperature will be between 35 to 37 C; if patients find the gas temperature to be uncomfortable, it can be lowered as necessary down to 33 C to enhance tolerance. FIO2 will be 1.0 initially to assure adequate oxygenation, but should be adjusted promptly to maintain an FIO2 of no greater than 0.6 to maintain a PaO2 > 88%.	Device: Vapotherm; Patients will be fit with a Vapotherm adult nasal cannula that will be applied by a respiratory therapist or other clinician skilled in management of HFT. Initial flow will be set to 35 L/min but can be decreased or increased as rapidly as necessary to alleviate respiratory distress and optimize patient comfort. Targets should be to lower respiratory rate to the low 20s and with a HFT flow rate between 20 to 35 L/min. Starting temperature will be between 35 to 37 C; if patients find the gas temperature to be uncomfortable, it can be lowered as necessary down to 33 C to enhance tolerance. FIO2 will be 1.0 initially to assure adequate oxygenation, but should be adjusted promptly to maintain an FIO2 of no greater than 0.6 to maintain a PaO2 > 88%.; Other Names: High flow nasal cannula

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment Failure Rate	Determine the efficacy of HFT compared to NIPPV in treating respiratory failure. The primary endpoint will be treatment failure within 72 hrs as determined by intubation.	Within 72 hrs

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ventilatory Indices 1	Evaluate the capability of high velocity nasal insufflation (HVNI), compared to non-invasive positive pressure ventialtion (NIPPV), to affect indices of ventilation. The secondary endpoint is the degree of physiologic improvement in blood oxygen and CO2 levels that signify a reduction in both hypoxemia and/or hypercapnia.	At one and four hours baseline, 30min, 1 hr, 90 min, and 4 hrs (if still on therapy) and at treatment failure/intubation (if applicable).
Ventilatory Indices 2	Evaluate the capability of high velocity nasal insufflation (HVNI), compared to non-invasive positive pressure ventilation (NIPPV), to affect indices of ventilation. The secondary endpoint is the degree of physiologic improvement in blood oxygen and CO2 levels that signify a reduction in both hypoxemia and/or hypercapnia. Respiratory rate recorded at one and four hours, and at treatment failure if applicable.	At baseline, 30 minutes, 60 minutes, 90 minutes, 4 hours, and treatment failure if applicable
Ventilatory Indices 3	Evaluate the capability of high velocity nasal insufflation (HVNI), compared to non-invasive positive pressure ventilation (NIPPV), to affect indices of ventilation. The secondary endpoint is the degree of improvement in blood oxygen and CO2 levels that signify a reduction in both hypoxemia and/or hypercapnia. SpO2 (a measurement of blood oxygen) recorded at baseline, 30min, 1 hr, 90 min, and 4 hrs (if still on therapy) and at treatment failure/intubation (if applicable).	At one and four hours baseline, 30min, 1 hr, 90 min, and 4 hrs (if still on therapy) and at treatment failure/intubation (if applicable).
Ventilatory Indices 4	Evaluate the capability of HFT, compared to NIPPV, to affect indices of ventilation. Patient discomfort as rated on a VAS recorded at one and four hours baseline, 30min, 1 hr, 90 min, and 4 hrs (if still on therapy) and at treatment failure/intubation (if applicable).. NOTE: Due to need for patients to be alert and provide this rating, the number analyzed is less than the total patients in the trial. VAS: Visual Analogue Scale. A Likert scale of facial expressions ranging from a smiley face to a frowning face used to assess the subjects' subjective level of dyspnea. Minimum 0 (no discomfort) to Maximum 5 (maximum discomfort).	At one and four hours baseline, 30min, 1 hr, 90 min, and 4 hrs (if still on therapy) and at treatment failure/intubation (if applicable).
Ventilatory Indices 5	Evaluate the capability of HVNI, compared to NIPPV, to affect indices of ventilation. The secondary endpoint is the degree of physiologic improvement in blood oxygen and CO2 levels that signify a reduction in both hypoxemia and/or hypercapnia. Modified Borg score recorded at baseline, 30min, 1 hr, 90 min, and 4 hrs (if still on therapy) and at treatment failure/intubation (if applicable). NOTE: Due to the need for patients to be alert and able to provide this score, the number analyzed is less than the total patients in the trial. A modified Borg scale was used to ask the patient to describe their effort on a scale of 0 to 10, where 10 is extreme discomfort.	at baseline, 30min, 1 hr, 90 min, and 4 hrs (if still on therapy) and at treatment failure/intubation (if applicable)
Ventilatory Indices 6	Evaluate the capability of HVNI, compared to NIPPV, to affect indices of ventilation. The secondary endpoint is the degree of improvement in blood oxygen and CO2 levels that signify a reduction in both hypoxemia and/or hypercapnia. Blood gas (pH), a measurement of CO2 levels, recorded at one and four hours, and at treatment failure if applicable. NOTE: Due to test error, the number analyzed is less than the total patients in the trial.	At one and four hours
Ventilatory Indices 7	Evaluate the capability of HVNI, compared to NIPPV, to affect indices of ventilation. The secondary endpoint is the degree of improvement in blood oxygen and CO2 levels that signify a reduction in both hypoxemia and/or hypercapnia. Blood gas (PCO2), a measure of CO2, recorded at one and four hours, and at treatment failure if applicable. NOTE: Due to test error, the number analyzed is less than the total patients in the trial.	At one and four hours
Ventilatory Indices 8	Evaluate the capability of HVNI, compared to NIPPV, to affect indices of ventilation. The secondary endpoint is the degree of physiologic improvement in blood oxygen and CO2 levels that signify a reduction in both hypoxemia and/or hypercapnia. Blood gas (HCO3), a meausre of blood oxygen/CO2 levels, recorded at one and four hours, and at treatment failure if applicable. NOTE: Due to test error, the number analyzed is less than the total patients in the trial.	At one and four hours
Ventilatory Indices 9	Evaluate the capability of HVNI, compared to NIPPV, to affect indices of ventilation. The secondary endpoint is the degree of physiologic improvement in blood oxygen and CO2 levels that signify a reduction in both hypoxemia and/or hypercapnia. Blood gas (base excess), a measure of blood oxygen/CO2 levels, recorded at one and four hours, and at treatment failure if applicable. NOTE: Due to test error, the number analyzed is less than the total patients in the trial.	At one and four hours
Length of Stay	Evaluate the capability of HVNI, compared to NIPPV, to affect average length of stay.	Duration of hospital visit

Collaborators and Investigators

• Sponsor: Vapotherm, Inc.
• Collaborators: University of Texas; University of Tennessee; Memorial Hermann Texas Medical Center; Piedmont Athens Regional Medical Center; Erlanger Medical Center; Memorial Hermann The Woodlands; McLeod Regional Medical Center
• Investigators: Principal Investigator: Pratik B Doshi, MD, University of Texas; Study Director: Thomas L Miller, PhD, Vapotherm, Inc.

Publications and helpful links

General Publications

• Doshi P, Whittle JS, Bublewicz M, Kearney J, Ashe T, Graham R, Salazar S, Ellis TW Jr, Maynard D, Dennis R, Tillotson A, Hill M, Granado M, Gordon N, Dunlap C, Spivey S, Miller TL. High-Velocity Nasal Insufflation in the Treatment of Respiratory Failure: A Randomized Clinical Trial. Ann Emerg Med. 2018 Jul;72(1):73-83.e5. doi: 10.1016/j.annemergmed.2017.12.006. Epub 2018 Jan 6.

Study record dates

Study Major Dates

• Study Start: September 1, 2014
• Primary Completion (Actual): September 1, 2016
• Study Completion (Actual): February 1, 2017

Study Registration Dates

• First Submitted: September 8, 2014
• First Submitted That Met QC Criteria: September 9, 2014
• First Posted (Estimate): September 10, 2014

Study Record Updates

• Last Update Posted (Actual): May 23, 2019
• Last Update Submitted That Met QC Criteria: April 25, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: noninvasive ventilation; high flow nasal cannula; acute respiratory failure; high flow therapy
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Respiratory Insufficiency
• Other Study ID Numbers: RP-EDPF2014001Dev