The Role of Gas Flow in Transnasal Pulmonary Aerosol Delivery: A Double-blinded, Randomized Controlled Trial

COPD Asthma Clinical Trial

Official title:

Investigating the Role of Gas Flow in Transnasal Pulmonary Aerosol Delivery Via Nasal Cannula: A Double-blinded, Randomized Controlled Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03739359
• Other study ID #: HFNC-PFT-002
• Status: Completed
• Phase: N/A
• Start date: February 1, 2019
• Est. completion date: December 1, 2019

Study information

• Verified date: March 2020
• Source: Rush University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Aerosol delivery via nasal cannula has gained increasing popularity, due to its combined benefits from aerosolized medication and heated warm oxygen therapy. In our previous in vitro study, we investigated the effects of the ratio of nasal cannula gas flow to subject's peak inspiratory flow (GF: IF) on the aerosol lung deposition, and we found that aerosol deposition in lung increased as the GF: IF decreased with an optimal GF: IF between 0.1 to 0.5 producing a stable "lung" deposition in both quiet and distress breathing. Thus we aimed to further validate such an optimal GF: IF in patients with reversible airflow limitations by the delivery of bronchodilators. Adult COPD or asthma patients who met ATS/ERS criteria for bronchodilator response in pulmonary function lab will be recruited and consented. After a washout period (1-3 days), patients will receive an escalating doubling dosage (0.5, 1, 2, and 4mg) of albuterol in total volume of 2mL, delivered by mesh nebulizer via nasal cannula. Patients will be randomly assigned to inhale bronchodilator into 3 group using different flows: 50 L/min,GF: IF = 1.0, and GF: IF = 0.5.

Description:

Introduction Both in vitro and in vivo radiolabeled studies on nebulization via high flow nasal cannula (HFNC) showed that aerosol lung deposition decreased with the increasing nasal cannula gas flow, which, however, was not observed in patients with distressed breathing. In our previous in vitro study, we investigated the effects of the ratio of nasal cannula gas flow to subject's peak inspiratory flow (GF: IF) on the aerosol lung deposition, and we found that aerosol deposition in lung increased as the GF: IF decreased with an optimal GF: IF between 0.1 to 0.5 producing a stable "lung" deposition in both quiet and distress breathing. Thus we aimed to further validate such an optimal GF: IF in patients with reversible airflow limitations by the delivery of bronchodilators.

Methods and analysis COPD and asthma patients with positive response to four actuations of albuterol via metered dose inhaler (MDI) and valved holding chamber (VHC) will be enrolled and consented in the study. After a washout period (1-3 days), patients will be randomly assigned to three groups with different nasal cannula gas flow: 50L/min, GF: IF = 1.0, and GF: IF = 0.5. In each treatment arm, patients will firstly receive saline, then followed by an escalating doubling dosages (0.5, 1, 2, and 4mg) of albuterol in a total volume of 2mL, delivered by mesh nebulizer (VMN, Aerogen, Ireland) via heated nasal cannula at 37℃. An interval of 30 min will be maintained between two doses of albuterol, and pulmonary spirometry will be measured at baseline and after each dose. Titration will be terminated when an additional FEV1 improvement was < 5%.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 75
• Est. completion date: December 1, 2019
• Est. primary completion date: December 1, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

Inclusion Criteria:

Adult patients with positive bronchodilator responses to four actuations of albuterol (Ventolin, GSK, UK) via MDI with VHC (OptiChamber Diamond, Philips, USA) will be eligible for enrollment. A positive bronchodilator response is defined in accordance with ATS/ERS guidelines as follows: an increase in FEV1 of = 12% and absolute change = 200 mL from baseline.

Exclusion Criteria:

• age = 90 years old;

• pregnancy;

• pulmonary exacerbation within two weeks before enrollment;

• reluctant to participate;

• inability to complete the follow-up spirometry after each bronchodilator inhalation;

• resting heart rate > 100bpm;

• resting systolic blood pressure > 160mmHg or diastolic blood pressure > 110mmHg.

Related Conditions & MeSH terms

• COPD Asthma

Intervention

Other:
• nasal cannula gas flow
High flow nasal cannula (HFNC) is a relatively new oxygen device, which provides warmed and humidified oxygen for patients. When patients need to inhale aerosolized medication during HFNC, the nebulizer will be placed in-line in order to provide both treatments. This study will investigate the influence of three flow settings (50 L/min, GF:IF=1, GF:IF=0.5) on the clinical effects of nebulization.

Locations

Country	Name	City	State
China	People's Liberation Army General Hospital	Beijing	Beijing

Sponsors (2)

Lead Sponsor	Collaborator
Rush University Medical Center	People's Liberation Army General Hospital

Country where clinical trial is conducted

China, 

References & Publications (5)

Ammar MA, Sasidhar M, Lam SW. Inhaled Epoprostenol Through Noninvasive Routes of Ventilator Support Systems. Ann Pharmacother. 2018 Dec;52(12):1173-1181. doi: 10.1177/1060028018782209. Epub 2018 Jun 12. — View Citation

Bräunlich J, Wirtz H. Oral Versus Nasal High-Flow Bronchodilator Inhalation in Chronic Obstructive Pulmonary Disease. J Aerosol Med Pulm Drug Deliv. 2018 Aug;31(4):248-254. doi: 10.1089/jamp.2017.1432. Epub 2017 Dec 20. — View Citation

Dugernier J, Hesse M, Jumetz T, Bialais E, Roeseler J, Depoortere V, Michotte JB, Wittebole X, Ehrmann S, Laterre PF, Jamar F, Reychler G. Aerosol Delivery with Two Nebulizers Through High-Flow Nasal Cannula: A Randomized Cross-Over Single-Photon Emission — View Citation

Gacouin A, Maamar A, Fillatre P, Sylvestre E, Dolan M, Le Tulzo Y, Tadié JM. Patients with preexisting psychiatric disorders admitted to ICU: a descriptive and retrospective cohort study. Ann Intensive Care. 2017 Dec;7(1):1. doi: 10.1186/s13613-016-0221-x — View Citation

Zhu Y, Yin H, Zhang R, Wei J. High-flow nasal cannula oxygen therapy versus conventional oxygen therapy in patients with acute respiratory failure: a systematic review and meta-analysis of randomized controlled trials. BMC Pulm Med. 2017 Dec 13;17(1):201. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The number of patients who meet the positive criteria of responding to albuterol at the dose of 0.5mg	The number of patients in HFNC nebulization who respond to albuterol at the dose of 0.5mg	30 minutes
Primary	The number of patients who meet the positive criteria of responding to albuterol at the dose of 1.5 mg	The number of patients in HFNC nebulization who respond to albuterol at the dose of 1.5mg	60 minutes
Primary	The number of patients who meet the positive criteria of responding to albuterol at the dose of 3.5 mg	The number of patients in HFNC nebulization who respond to albuterol at the dose of 3.5mg	90 minutes
Primary	The number of patients who meet the positive criteria of responding to albuterol at the dose of 7.5mg	The number of patients in HFNC nebulization who respond to albuterol at the dose of 7.5mg	120 minutes
Secondary	the accumulative dose of albuterol required across groups to produce positive bronchodilation effects	the accumulative dose of albuterol required to produce positive bronchodilation effects in each group	120 minutes
Secondary	the incidence of side effect (tachycardia) in each group	the incidence of side effect (tachycardia) will be recorded in each group	120 minutes
Secondary	the incidence of side effect (tremor) in each group	the incidence of side effect (tachycardia) will be recorded in each group	120 minutes