NIV for Hypercapnic Respiratory Failure: AVAPS vs S/T BIPAP

Study Overview
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Brief Summary
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The goal of this study is to compare two different modes of noninvasive ventilation in hypercapnic respiratory failure. The investigators will compare AVAPS and BIPAP S/T and hypothesize that AVAPS will result in a decreased length of stay in the ICU or on telemetry. Currently, noninvasive ventilation is the standard of care for hypercapnic respiratory failure. However, the most effective mode for patients with hypercapnic respiratory failure is unclear.

Detailed Description
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1. Overall Study Design and Plan This is a single center, randomized trial that will include a total of 100 adult subjects aged 18 or older with hypercapnic respiratory failure of all etiologies (i.e. all comers). The investigators will randomize patients in a single-blinded (patient blinded) fashion to BIPAP S/T or AVAPS during the duration of their hospitalization. The investigators will assess ABG at baseline, 1 hour after initial placement on BIPAP S/T or AVAPS, and between hours 24-48 of use. The investigators will record the pre-NIV pH and PaCO2, post-NIV pH and PaCO2, length of hospital stay in the medical ICU or telemetry unit, days on NIV, need for intubation (if occurred), transition to medical ICU care in patients who were initially admitted to telemetry, and in-hospital mortality. All collected laboratory data are already done as part of usual care for all patients placed on NIV when a patient is on the telemetry unit or medical ICU. The groups will undergo stratified randomization based on whether they are initially admitted to medical ICU or medical telemetry. Patients from medical ICU or telemetry units will be randomized to one of the following arms: Arm 1: AVAPS mode Arm 2 2: BIPAP S/T mode

Official Title
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NIV for Hypercapnic Respiratory Failure: AVAPS vs S/T BIPAP

Conditions
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Hypercapnic Respiratory Failure

Intervention / Treatment
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* Device: Average Volume-Assured Pressure Support (AVAPS)
* Device: Bilevel Positive Airway Pressure Spontaneous Timed (BIPAP S/T)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provision of signed and dated informed consent form directly by the patient; consent can also be obtained via a legal patient representative/health care proxy/surrogate Stated willingness to comply with all study procedures and availability for the duration of the study Male or female, aged 18 or older Diagnosed with hypercapnic respiratory failure on admission (ABG) Admitted to Lenox Hill Hospital medical intensive care unit or telemetry unit Requiring noninvasive ventilation as determined by the treating physician for the treatment of hypercarbic respiratory failure Exclusion Criteria: Patients who require ventilation at predetermined tidal volumes Patients who require rapid and frequent IPAP adjustments to maintain a consistent tidal volume Age less than 18 years of age Currently intubated Chronic tracheostomy Pregnancy Hypotension Epistaxis (nosebleed) Untreated pertussis Acute sinusitis or Otitis media Patients at risk of aspirating gastric contents Patients with lack of spontaneous respiratory drive Patients with the inability to maintain a patent airway or adequately clear secretions Prisoners or other institutionalized individuals

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Patients from medical ICU or telemetry units will be randomized to one of the following arms: Arm 1: AVAPS mode Arm 2: BIPAP S/T mode
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Average Volume-Assured Pressure Support (AVAPS)<br>Average Volume-Assured Pressure Support (AVAPS) setting on the noninvasive ventilator. The exact AVAPS setting will be titrated by the clinical team involved directly in the patient's care based on patient comfort and clinical response. | Device: Average Volume-Assured Pressure Support (AVAPS)<br>* A setting on noninvasive ventilator that allows setting of maximum and minimum inspiratory pressure and sets a target tidal volume. The inspiratory pressure varies breath to breath to ensure pre-set tidal volume is delivered.<br>|
| Active Comparator: Bilevel Positive Airway Pressure Spontaneous Timed (BIPAP S/T)<br>Bilevel Positive Airway Pressure Spontaneous Timed (BIPAP S/T) setting on the noninvasive ventilator. The exact BIPAP S/T setting will be titrated by the clinical team involved directly in the patient's care based on patient comfort and clinical response. | Device: Bilevel Positive Airway Pressure Spontaneous Timed (BIPAP S/T)<br>* A setting on noninvasive ventilator that allows setting of inspiratory pressure, inspiratory time, expiratory pressure, and backup rate to deliver variable tidal volumes.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ICU length of stay of telemetry length of stay | In patients admitted to the medical ICU, the primary endpoint is ICU length of stay. This will be the number of days a patient is admitted from day 1 of admission until the day of discharge. In patients admitted to medical telemetry unit, the outcome is telemetry length of stay. This will be the number of days a patient is admitted from day 1 of admission until the day of discharge. | within one week of hospital discharge (5-7 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in PaCO2 value with NIV | Change in paCO2 on ABG (paCO2 before and after NIV use, measured as a numerical value in mmHg) | within 24-48 hours after noninvasive ventilation | 
| Time to normalization of pH | Time to normalization of pH (hours) | at the time of hospital discharge (an average of 5-7 days) | 
| Normalization of pH | Return to normal range of pH as defined by the laboratory normal values (Binary measure) | at the time of hospital discharge (an average of 5-7 days) | 
| Days on NIV | Days on noninvasive ventilation | within one week of hospital discharge (5-7 days) | 
| Need for intubation | Need for intubation | within one week of hospital discharge (5-7 days) | 
| Need for ICU stay | Need for ICU stay (if disposition changed from telemetry unit) | within one week of hospital discharge (5-7 days) | 
| Subgroup analysis (logistic regression or p-value) comparing outcomes 1- ICU or telemetry length of stay based on the underlying cause of hypercapnic respiratory failure | We will perform subgroup analysis of each cause of hypercapnic respiratory failure (such as COPD, pulmonary edema, altered mental status, etc) for these outcome- for 1. ICU or telemetry length of stay. We will use either logistic regression model or p-value to determine the difference for each subgroup. The results will be reported as difference between groups with statistical significance. | through study completion, an average of 1 year | 
| Subgroup analysis (logistic regression or p-value) comparing outcome 2- difference in paCO2 reported as difference between groups (with p-value and/or standard deviation) | We will perform subgroup analysis of each cause of hypercapnic respiratory failure (such as COPD, pulmonary edema, altered mental status, etc) for outcome 2- difference in PaCO2. We will use either logistic regression model or p-value to determine the difference for each subgroup. The results will be reported as difference between groups with statistical significance. | through study completion, an average of 1 year | 
| Subgroup analysis (logistic regression or p-value) comparing outcome 4- time to normalization of pH reported as difference between groups (with p-value and/or standard deviation) | We will perform subgroup analysis of each cause of hypercapnic respiratory failure (such as COPD, pulmonary edema, altered mental status, etc) for outcome 4- time to normalization of pH. We will use either logistic regression model or p-value to determine the difference for each subgroup. The results will be reported as difference between groups with statistical significance. | through study completion, an average of 1 year | 
| Subgroup analysis (logistic regression or p-value) comparing outcome 5- days on NIV reported as difference between groups (with p-value and/or standard deviation) | We will perform subgroup analysis of each cause of hypercapnic respiratory failure (such as COPD, pulmonary edema, altered mental status, etc) for outcome 5- days on NIV. We will use either logistic regression model or p-value to determine the difference for each subgroup. The results will be reported as difference between groups with statistical significance. | through study completion, an average of 1 year | 
| Subgroup analysis (logistic regression or p-value) comparing outcome 6- need for intubation reported as difference between groups (with p-value and/or standard deviation) | We will perform subgroup analysis of each cause of hypercapnic respiratory failure (such as COPD, pulmonary edema, altered mental status, etc) for outcome 6- need for intubation. We will use either logistic regression model or p-value to determine the difference for each subgroup. The results will be reported as difference between groups with statistical significance. | through study completion, an average of 1 year | 
| Subgroup analysis (logistic regression or p-value) comparing outcome 7- need for ICU stay reported as difference between groups (with p-value and/or standard deviation) | We will perform subgroup analysis of each cause of hypercapnic respiratory failure (such as COPD, pulmonary edema, altered mental status, etc) for outcome 7- need for ICU stay. We will use either logistic regression model or p-value to determine the difference for each subgroup. The results will be reported as difference between groups with statistical significance. | through study completion, an average of 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AVAPS, BIPAP, Hypercapnic respiratory failure, Noninvasive ventilation