Nebulizer Versus Dry Powdered Inhalers for Chronic Obstructive Pulmonary Disease (COPD)

COPD Clinical Trial

Official title:

Preliminary Study for Comparison of Triple Therapy Nebulizer Versus Dry Powdered Inhaler for Care Transitions in COPD

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03219866
• Other study ID #: IRB00042362
• Status: Terminated
• Phase: Phase 4
• Start date: October 3, 2017
• Est. completion date: April 1, 2020

Study information

• Verified date: September 2020
• Source: Wake Forest University Health Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This will be a non-blinded feasibility (pilot) study comparing triple therapy nebulizer vs dry powdered inhalers (DPI) for care transitions in Chronic obstructive pulmonary disease (COPD) exacerbation patients. We hypothesize that patients treated in hospital and discharged on respiratory medications administered by nebulizers will exhibit better quality of life (QoL), symptom control, and lower COPD and all cause hospital readmission rates compared with patients treated with respiratory medications delivered by DPI. We aim to demonstrate that: 1. Patients treated and discharged on nebulized bronchodilators will have fewer readmissions to hospital at 30 and 90 days compared to the group utilizing DPI 2. The nebulizer group will demonstrate a longer duration of time until hospital readmission for COPD and all cause readmission compared to the group utilizing DPI 3. The nebulizer group will demonstrate better QoL (measured by the SGRQ - Saint George Respiratory Questionnaire) and symptom control (as measured by the CAT & mMRC) compared to the group utilizing DPI.

Description:

Drugs used to treat Chronic obstructive pulmonary disease (COPD) are available primarily in hand held inhaler devices that deliver dry powder (DPI), a soft mist or a metered dose of spray (MDI). The frail, arthritic elderly are often prescribed DPI rather than MDI or soft mist devices, because they require less coordination. DPIs however require the ability to inhale against a resistance with a peak inspiratory force (PIF) more negative than 60 L/min to break the dry powder into respirable particles. Preliminary data suggests that suboptimal PIF's are common during an acute exacerbation of COPD, affecting 48% of hospitalized patients, thus placing them at risk for treatment failure and possibly hospital readmission. Use of nebulizers to administer respiratory medications may avoid the hazards of insufficient dosing that can result from use of DPI however they are cumbersome, expensive and the variety of drugs available in a nebulizer format is limited. We hypothesize that patients treated in hospital and is charged on respiratory medications administered by nebulizers will exhibit better symptom control and lower COPD and all cause hospital readmission rates compared with patients treated with respiratory medications delivered by DPI. We aim to demonstrate that 1) patients treated and discharged on nebulized bronchodilators will have fewer readmissions to hospital at 30 and 90 days compared to the group utilizing DPI 2) that the nebulizer group will demonstrate a longer duration of time till hospital readmission for COPD and all cause readmission compared to the group utilizing DPI and 3) the nebulizer group will demonstrate better symptom control compared to the group utilizing DPI. This nonblinded feasibility (pilot) study will enroll 100 patients hospitalized for an exacerbation of COPD who are > 40 years of age, have a clinical diagnosis of COPD. The study will consist of 3 outpatient visits (Transitional Care Visit [314 days after discharge], Visit #2 [30 +/5 days after discharge], and Visit #3 [90 +/5 days after discharge]). Visit #2 and #3 are for study purposes, the Transitional Care Visit is standard of care. We hypothesize and aim to demonstrate that patients treated in hospital and discharged on respiratory medications administered by nebulizers will exhibit better quality of life (QoL), symptom control and lower COPD and all cause hospital readmission rates compared with patients treated with respiratory medications delivered by DPI.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 40
• Est. completion date: April 1, 2020
• Est. primary completion date: April 1, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years and older

Eligibility

Inclusion Criteria:

• > 40 years of age
• Clinical diagnosis of COPD
• Smoking history > 10 pack years
• Lung Function- FEV1/FVC or FEV1/SVC < 70% on bedside spirometry or previous baseline and FEV1/FVC or FEV1/SVC < 70% on clinic visit < 2 weeks from discontinuation
• Able to give informed consent

Exclusion Criteria:

• Dementia
• Active cancer
• End stage cardiovascular disease
• Inability to attend outpatient visits
• Active Schizophrenia Pregnancy; subjects will be excluded if female and are not post-menopausal for at least one year. Since there is no possible benefit from participating in this protocol for a pregnant woman, we will exclude pregnant women. If a subject is found to be pregnant during the 90-day study period, they will be excluded from the study and their data not used for study purposes.

Related Conditions & MeSH terms

• COPD
• COPD Exacerbation
• Pulmonary Disease, Chronic Obstructive

Intervention

Device:
• Nebulizers
Patients treated and discharged on nebulized bronchodilators
• Dry Powder Inhaler
Patients treated and discharged on Dry Powder Inhalers

Drug:
• Brovana
Subjects will receive a long-acting B2-agonist(LABA; Brovana, twice daily)
• Pulmicort
Subjects will receive a corticosteroid (ICS; Pulmicort, twice daily)
• Atrovent
Subjects will receive a short-acting anti-cholinergic (SAMA; Atrovent, three times a day)
• Advair Diskus
Subjects will receive a LABA/ICS (Advair Diskus, twice daily)
• Spiriva HandiHaler
Subjects will receive a long-acting anticholinergic (LAMA-Spiriva Handihaler, once daily)

Locations

Country	Name	City	State
United States	Wake Forest Baptist Health	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Wake Forest University Health Sciences

Country where clinical trial is conducted

United States, 

References & Publications (12)

Calverley PM, Rabe KF, Goehring UM, Kristiansen S, Fabbri LM, Martinez FJ; M2-124 and M2-125 study groups. Roflumilast in symptomatic chronic obstructive pulmonary disease: two randomised clinical trials. Lancet. 2009 Aug 29;374(9691):685-94. doi: 10.1016/S0140-6736(09)61255-1. Erratum in: Lancet. 2010 Oct 2;376(9747):1146. — View Citation

Cazzola M, Molimard M. The scientific rationale for combining long-acting beta2-agonists and muscarinic antagonists in COPD. Pulm Pharmacol Ther. 2010 Aug;23(4):257-67. doi: 10.1016/j.pupt.2010.03.003. Epub 2010 Apr 8. Review. — View Citation

Cazzola M, Page CP, Calzetta L, Matera MG. Pharmacology and therapeutics of bronchodilators. Pharmacol Rev. 2012 Jul;64(3):450-504. doi: 10.1124/pr.111.004580. Epub 2012 May 18. Review. — View Citation

Centers for Disease Control and Prevention (CDC). Chronic obstructive pulmonary disease among adults--United States, 2011. MMWR Morb Mortal Wkly Rep. 2012 Nov 23;61(46):938-43. — View Citation

Dransfield MT, Bourbeau J, Jones PW, Hanania NA, Mahler DA, Vestbo J, Wachtel A, Martinez FJ, Barnhart F, Sanford L, Lettis S, Crim C, Calverley PM. Once-daily inhaled fluticasone furoate and vilanterol versus vilanterol only for prevention of exacerbations of COPD: two replicate double-blind, parallel-group, randomised controlled trials. Lancet Respir Med. 2013 May;1(3):210-23. doi: 10.1016/S2213-2600(13)70040-7. Epub 2013 Apr 12. Erratum in: Lancet Respir Med. 2013 May;1(3):186. — View Citation

Ferguson GT, Anzueto A, Fei R, Emmett A, Knobil K, Kalberg C. Effect of fluticasone propionate/salmeterol (250/50 microg) or salmeterol (50 microg) on COPD exacerbations. Respir Med. 2008 Aug;102(8):1099-108. doi: 10.1016/j.rmed.2008.04.019. Epub 2008 Jul 9. — View Citation

Guarascio AJ, Ray SM, Finch CK, Self TH. The clinical and economic burden of chronic obstructive pulmonary disease in the USA. Clinicoecon Outcomes Res. 2013 Jun 17;5:235-45. doi: 10.2147/CEOR.S34321. Print 2013. — View Citation

Loh CH, Lovings T, Ohar JA . Low Inspiratory Flow Rates Predict COPD and All Cause Readmissions. ATS Abstract;2016;In press

Mahler DA, Waterman LA, Gifford AH. Prevalence and COPD phenotype for a suboptimal peak inspiratory flow rate against the simulated resistance of the Diskus® dry powder inhaler. J Aerosol Med Pulm Drug Deliv. 2013 Jun;26(3):174-9. doi: 10.1089/jamp.2012.0987. Epub 2012 Oct 1. — View Citation

Pauwels RA, Buist AS, Ma P, Jenkins CR, Hurd SS; GOLD Scientific Committee. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: National Heart, Lung, and Blood Institute and World Health Organization Global Initiative for Chronic Obstructive Lung Disease (GOLD): executive summary. Respir Care. 2001 Aug;46(8):798-825. Review. — View Citation

Pleasants RA, Ohar JA, Croft JB, Liu Y, Kraft M, Mannino DM, Donohue JF, Herrick HL. Chronic obstructive pulmonary disease and asthma-patient characteristics and health impairment. COPD. 2014 Jun;11(3):256-66. doi: 10.3109/15412555.2013.840571. Epub 2013 Oct 23. — View Citation

Tashkin DP, Celli B, Senn S, Burkhart D, Kesten S, Menjoge S, Decramer M; UPLIFT Study Investigators. A 4-year trial of tiotropium in chronic obstructive pulmonary disease. N Engl J Med. 2008 Oct 9;359(15):1543-54. doi: 10.1056/NEJMoa0805800. Epub 2008 Oct 5. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Quality of Life Measured by St. George's Respiratory Questionnaire (SGRQ)	Scores range from 0 to 100, with higher scores indicating more limitations - Symptoms component (frequency & severity) with a 1, 3 or 12-month recall (best performance with 3- and 12-month recall); Part 2: Activities that cause or are limited by breathlessness; Impact components (social functioning, psychological disturbances resulting from airways disease) refer to current state as the recall	90 Days
Secondary	Symptom Control Measured by the COPD Assessment Test (CAT)	The COPD Assessment Test (CAT) is a patient-completed instrument that can quantify the impact of COPD on the patient's health. The CAT is a validated, short (8-item) and simple patient completed questionnaire. The CAT has a scoring range of 0-40 and a difference or change of 2 or more units over 2 to 3 months in a patient suggests a clinically significant difference or change in health status. A score of >30 indicates that COPD has a very high impact on daily life, a score of >20 indicates a high impact, 10-20 is medium impact, <10 is low impact, and 5 is the upper limit for healthy non-smokers. A higher score would represent a poor outcome for this test.	90 Days
Secondary	Symptom Control Measured by The Modified Medical Research Council Dyspnea Scale (mMRC)	The Modified Medical Research Council Dyspnea Scale, or MMRC, uses a simple grading system to assess a patient's level of dyspnea -- shortness of breath. The scale goes from 0-4 with a 0 = I only get breathless with strenuous exercise, 1 = I get short of breath when hurrying on level ground or walking up a slight hill, 2 = On level ground, I walk slower than people of the same age because of breathlessness or have to stop for breath when walking at my own pace, 3 = I stop for breath after walking about 100 yards or after a few minutes on level ground, and 4 = I am too breathless to leave the house or I am breathless when dressing. 4 would represent the worst outcome.	90 Days
Secondary	COPD and All-Cause Hospital Readmissions After 30 Days	Compare the number of hospital readmissions between the two arms after 30 days of using each device.	30 Days
Secondary	COPD and All-Cause Hospital Readmissions After 90 Days	Compare the number of hospital readmissions between the two arms after 90 days of using each device.	90 Days
Secondary	Unscheduled Clinic or ER Visits	Compare the number of unscheduled clinic or ER visits between the two arms after 90 days of using each device	90 Days
Secondary	Change in Pulmonary Inspiratory Force (PIF) From Baseline at 90 Days - R -2 (Low to Medium Resistance Inhalers)	Pulmonary inspiratory force (PIF) from hospital baseline between the two arms for the duration of the 90 day study.	Baseline and 90 days
Secondary	Number of Deaths		90 days
Secondary	Change in Pulmonary Inspiratory Force (PIF) From Baseline at 90 Days - R -5 (High Resistance Inhalers)	Pulmonary inspiratory force (PIF) from hospital baseline between the two arms for the duration of the 90 day study.	Baseline and 90 days