In Line Aerosol Nebulization With High Flow

Study Overview
=================
Brief Summary
-----------------
The objective of ILAN is to assess the safety, feasibility and bronchodilator efficacy of in-line bronchodilator nebulizer delivery with VMN via HFNC system in hypoxemic respiratory failure patients treated with bronchodilators and compare this method to standard-nebulization using a jet nebulizer with a facial mask. The investigators hypothesized that aerosol nebulization using HFNC/VMN represents safer and more convenient approach in hypoxemic respiratory failure patients in comparison to conventional therapy while providing similar bronchodilator efficacy.

Detailed Description
-----------------
Objective: To evaluate the safety and feasibility of a novel approach to nebulization treatment via the nasal route in patients with severe hypoxemic respiratory failure dependent on high flow oxygen. Hypothesis: In-line vibrating mesh nebulizer delivery via HFNC systems is a safe, feasible and efficacious approach in comparison to traditional jet nebulizer delivered nebulization in hypoxemic respiratory failure patients whose usual care includes nebulized drugs. Specific Aims: To evaluate the safety and feasibility of administering vibrating mesh nebulizer-delivered therapy in patients with acute hypoxemic respiratory failure requiring high flow nasal cannula. To evaluate the effect of trans-nasal nebulization on patient comfort and satisfaction with therapy in comparison with standard jet nebulization. To evaluate differences in resource utilization between patients receiving standard jet nebulization and ILAN with HF, including time spent at the bedside by the respiratory therapist (RT) for delivery of the medication and any additional time gathering setting up and cleaning. To evaluate patient and therapist perceptions and preference on the various delivery methods of aerosol delivery. Study Design: ILAN is a double-crossover, multi-center trial evaluating the safety and feasibility of in line nebulized medication with high flow nasal canula in comparison to standard jet nebulizer therapy in acute respiratory failure requiring the utilization of high flow nasal cannula. Intervention: Enrolled patients will receive two standard forms of inhaled medications as ordered by the physician. Patients will be randomized into two paths of the cross over study. There will be no blinding involved in this randomization. Path A will have medications delivered trans-nasally in line via the vibrating mesh nebulizer (VMN) with the high flow nasal cannula followed by standard jet nebulization (SJN) with face mask at the next time of medication dosing 3-6 hours later. Path B will receive standard jet nebulization without HFNC followed by the trans-nasal in line nebulization via the HFNC. Patients selected to enroll in day 2 of the trial will have their clinical path alternated in attempt to control for diurnal variability. All patients will also receive as-needed nebulized treatments as well as usual supportive care provided by respiratory therapists. As needed therapy will be delivered via the method of the current arm of the study they are in, and the washout period will subsequently reset.

Official Title
-----------------
In Line Aerosol Nebulization With High Flow

Conditions
-----------------
Hypoxemic Respiratory Failure, Airway Obstruction

Intervention / Treatment
-----------------
* Device: nebulizer via in-line drug delivery maintaining high-flow nasal cannula oxygen
* Device: standard jet nebulization (SJN) with face mask


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Adults ≥ 18 years of age Patients with mild or moderate hypoxemic respiratory failure (with or without acute hypercapnic respiratory failure) treated with HFNC. Nebulizer therapy ordered by the primary team with at least one dose delivered prior to the enrollment into the study Patients must be on ordered nebulized albuterol, levalbuterol, ipratropium or ipratropium/albuterol combination with a maximum of Q3 or a minimum of Q6 hour frequencies. For Respiratory Therapists: They must be employees of SMICU or RRMC. Exclusion Criteria: Lack of hypoxemia defined as SpO2> 92% on room air Severe hypoxemia defined by PaO2/FiO2<100 or SpO2<92% on HFNC settings: ≥ FiO2 80% or higher and O2 flow 40L/min HFNC O2 delivery via tracheostomy COVID-19 positive status (within 3 weeks prior to the enrollment) Respiratory distress, defined by respiratory rate > 24 breath per minute Hemodynamic instability defined by the use of two or more vasopressor medications Presence of nasal obstruction that may pose a risk for inadequate nebulizer delivery in the opinion of the investigator Pulmonary comorbidities that, in the opinion of the investigator or clinical team, can pose a risk to subject safety or interfere with the subject's ability to complete the study procedures. Moribund patient not expected to survive >24 hours Inability to obtain informed consent from patient Respiratory therapists who are unwilling to participate.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: HFNC with trans-nasal aerosol delivery is a multi-center trial comparing nebulization of medications via trans-nasal delivery with vibrating mesh nebulizer to standard jet nebulization in patients with mild or moderate hypoxemic respiratory failure (with or without acute hypercapnic respiratory failure) treated with HFNC. The crossover nature of the study is reflected in the universal application of bronchodilators via both study interventions (HFNC/VMN and FM/SJN) in all subjects but in variable order depending on the randomization of subjects into Path A or Path B
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Path A (vibrating mesh nebulizer (VMN) with the high flow nasal cannula)<br>Enrolled patients will receive two standard forms of inhaled medications as ordered by the physician. Patients will be randomized into two paths of the cross over study. There will be no blinding involved in this randomization. Path A will have medications delivered trans-nasally in line via the vibrating mesh nebulizer (VMN) with the high flow nasal cannula followed by standard jet nebulization (SJN) with face mask at the next time of medication dosing 3-6 hours later. | Device: nebulizer via in-line drug delivery maintaining high-flow nasal cannula oxygen<br>* nebulized delivery of bronchodilator via in-line drug delivery maintaining high-flow nasal cannula oxygen<br>Device: standard jet nebulization (SJN) with face mask<br>* standard jet nebulization delivery of bronchodilator<br>|
| Active Comparator: Path B (standard jet nebulization (SJN) with face mask)<br>Path B will receive standard jet nebulization without HFNC followed by the trans-nasal in line nebulization via the HFNC. Patients agreed to enroll in day 2 of the trial will have their clinical path alternated in attempt to control for diurnal variability. All patients will also receive as-needed nebulized treatments as well as usual supportive care provided by respiratory therapists. As needed therapy will be delivered via the method of the current arm of the study they are in, and the washout period will subsequently reset. | Device: nebulizer via in-line drug delivery maintaining high-flow nasal cannula oxygen<br>* nebulized delivery of bronchodilator via in-line drug delivery maintaining high-flow nasal cannula oxygen<br>Device: standard jet nebulization (SJN) with face mask<br>* standard jet nebulization delivery of bronchodilator<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximal decrease in SpO2 during nebulization with jet nebulizer vs. inline via HFNC compared to the baseline SpO2 values prior to the nebulization therapy | Primary Outcome | up to 48 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with documented hypoxemia (<88%) during the nebulization | Safety Outcome | up to 48 hours | 
| Duration of hypoxemic episodes with SpO2<88% during the nebulization delivery | Safety Outcome | up to 48 hours | 
| Lowest absolute desaturation from the beginning until completion of nebulizer treatment compared to the baseline SpO2 values defined as the lowest adequately measured SpO2 within two minutes prior to the nebulization | Safety Outcome | up to 48 hours | 
| Increase in respiratory rate from the baseline during the nebulization by >10% | Safety Outcome | up to 48 hours | 
| Change in respiratory rate during nebulization compared to the baseline rate | Safety Outcome | up to 48 hours | 
| Requirement for additional interventions to maintain patient's safety during the nebulization | Safety Outcome: (Increased O2 flow (yes/know and rate increase) or increased O2 FiO2 (yes/know and rate increase) ) | up to 48 hours | 
| Need to increase O2 support after the nebulization therapy to maintain SpO2>88% | Safety Outcome | up to 48 hours | 
| Nosebleed within 2 hours of nebulizer delivery | Safety Outcome | up to 48 hours | 
| ROX score | Safety Outcome (While not externally validated, the ROX Index is a simple bedside calculation using three clinical variables and is one easy way to summarize a patient's degree of hypoxemic respiratory failure - gives risk of intubation - low to high) | up to 48 hours |