Clinical trial NCT03219866: Nebulizer Versus Dry Powdered Inhalers for Chronic Obstructive Pulmonary Disease (COPD)
Official title: Preliminary Study for Comparison of Triple Therapy Nebulizer Versus Dry Powdered Inhaler for Care Transitions in COPD
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: COPD
COPD Exacerbation
Keywords: Nebulizer
Inhaler
Lead sponsor: Wake Forest University Health Sciences
Sponsor class: OTHER
First posted: 2017-07-18
Enrollment: 40
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Quality of Life Measured by St. George's Respiratory Questionnaire (SGRQ)
timeFrame: 90 Days
Secondary outcomes:
measure: Symptom Control Measured by the COPD Assessment Test (CAT)
timeFrame: 90 Days
measure: Symptom Control Measured by The Modified Medical Research Council Dyspnea Scale (mMRC)
timeFrame: 90 Days
measure: COPD and All-Cause Hospital Readmissions After 30 Days
timeFrame: 30 Days
measure: COPD and All-Cause Hospital Readmissions After 90 Days
timeFrame: 90 Days
measure: Unscheduled Clinic or ER Visits
timeFrame: 90 Days
measure: Change in Pulmonary Inspiratory Force (PIF) From Baseline at 90 Days - R -2 (Low to Medium Resistance Inhalers)
timeFrame: Baseline and 90 days
measure: Number of Deaths
timeFrame: 90 days
measure: Change in Pulmonary Inspiratory Force (PIF) From Baseline at 90 Days - R -5 (High Resistance Inhalers)
timeFrame: Baseline and 90 days
Other outcomes:
Locations:
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Health
state: North Carolina
Study officials:
affiliation: Professor of Internal Medicine
name: Jill A Ohar, MD, FCCP
role: PRINCIPAL_INVESTIGATOR
References:
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.
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. No abstract available.
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.
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.
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.
citation: 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.
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.
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.
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.
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.
citation: Mahler DA, Waterman LA, Gifford AH. Prevalence and COPD phenotype for a suboptimal peak inspiratory flow rate against the simulated resistance of the Diskus(R) 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.
citation: Loh CH, Lovings T, Ohar JA . Low Inspiratory Flow Rates Predict COPD and All Cause Readmissions. ATS Abstract;2016;In press