Clinical trial NCT05292053: Outcomes of Once-Daily ICS/LABA/LAMA Plus PRN Respiratory Therapy Treatments in Hospitalized Patients With COPD Exacerbations
Official title: Establishing Outcomes of Once-Daily ICS/LABA/LAMA Plus PRN Respiratory Therapy Treatments in Hospitalized Patients With COPD Exacerbations (SUNDIAL-COPD)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Copd
Lead sponsor: Baylor Research Institute
Sponsor class: OTHER
First posted: 2022-03-23
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a single-center, prospective, open-label study evaluating outcomes of TRELEGY ELLIPTA (fluticasone furoate 100 mcg, umeclidinium 62.5 mcg, and vilanterol 25 mcg inhalation powder) on PRN nebulized short-acting beta agonist (SABA) treatment in hospitalized subjects with COPD with or without asthma.

Approximately 80 adult subjects with COPD with or without asthma will take part in this study at this location. Subjects will be given TRELEGY ELLIPTA, placed on a consistent short-term systemic corticosteroid therapy, and followed until 30 days post hospital discharge. This study will not include patients with rapidly deteriorating or potentially life-threatening episodes of COPD or asthma.

Detailed description: TRELEGY ELLIPTA is not prescribed as standard of care. Study participants will be consented prior to being prescribed TRELEGY ELLIPTA as part of this study.

Subjects will be given TRELEGY ELLIPTA once daily at the same time every day (± 2 hours). TRELEGY ELLIPTA will be initiated the morning of enrollment if feasible, or the morning following hospital enrollment otherwise. It will be administered as 1 inhalation by the orally inhaled route only.

When exacerbations of COPD that require hospitalization occur, short-acting bronchodilators (both beta agonists and anticholinergics) are routinely prescribed as part of a comprehensive regimen that includes supplemental oxygen, parenteral corticosteroids, antibiotics (usually), and if severe, non-invasive positive pressure ventilation. According to GOLD 2018 recommendations,2 long-acting bronchodilators are to be introduced as soon as possible prior to discharge from the hospital if not continued during hospitalization. However, the recommendation to use short-acting bronchodilators as a primary therapeutic inhalant is based on grade C level of evidence, suggesting a paucity of data to support that position. Primarily related to pharmacy-driven cost considerations, the exclusive use of short-acting bronchodilators has become the standard of care in treating hospitalized patients with COPD exacerbations, with the introduction of long-acting inhalants only upon discharge, by a number of institutions including Ben Taub Hospital in Houston (Nicola Hanania MD: personal communication), and throughout the Baylor Scott and White Healthcare System in Texas. This therapeutic substitution of short-acting for long-acting bronchodilators has been estimated to result in a cost savings of \~$400k at Baylor University Medical Center alone (personal communication: director of pharmacy services). Even so, few if any studies have evaluated the length of stay, in-hospital adverse events (nocturnal awakenings related to respiratory symptoms that occur beyond the window of pharmacologic efficacy of short-acting medications), respiratory therapy utilization or the potential impact upon re-hospitalizations with this paradigm shift of care. Sanford Hospital System in North Dakota recently published a study comparing a once daily long-acting combination with compared with a twice-daily combination and saw minimal cost savings and no real change in outcomes.3 This same system had previously studied substitution of twice daily beta agonist and once daily anticholinergic bronchodilators for combination short-acting bronchodilators and found improved outcomes and cost savings but reported their results in a non-peer reviewed journal in AARC Times, November 2011.

Results of an analysis of 60 patient charts randomly selected after hospitalization at Baylor University Medical Center for an exacerbation of underlying airways disease (greater than 90% with COPD) showed tremendous variation in practice patterns; with 30% of patients receiving short-acting beta-antagonists and muscarinic agonists (SABA/SAMA) only, 70% receiving long-acting beta-antagonists (LABA) with PRN SABA/SAMA, and only 42% receiving a long-acting muscarinic agonist (LAMA), despite practice guidelines encouraging the use of SABA/SAMA only (typically 4 times daily and as needed).

It is this large variability that renders the evaluation and interpretation of institution-specific outcomes difficult. The main impetus for the proposed study is therefore to establish a more standardized open-label protocol which would allow for a more accurate assessment of intervention outcomes. As one of several secondary goals of this study, the investigators aim to compare key outcomes (including, number of PRN treatments, length of hospital stay, and rate of readmission) with those from the historical cohort described above, when a combination LABA/LAMA/ICS inhaler is used as the primary scheduled daily inhaled therapy

Eligibility criteria: Inclusion Criteria:

* Willing and capable of providing written informed consent
* Subjects age 18 years or older at time of enrollment
* Diagnosis of COPD with or without asthma for 12 months or more.
* Hospitalized less than or equal to 24 hours prior to enrollment and currently hospitalized for COPD exacerbation with or without asthma
* Able to properly use the Ellipta medication delivery device
* Able to generate greater than or equal to 30 L/min inspiratory flow at screening, measured with an InCheck DIAL adjusted to medium low resistance, to document a subject's ability to effectively inhale medication delivered via an Ellipta device.

Exclusion Criteria:

* Clinically significant lung disease other than COPD with or without asthma
* Positive SARS-CoV-2 test at the time of ED or hospital admission, or any time between admission and enrollment.
* History of severe hypersensitivity to milk proteins or demonstrated hypersensitivity to fluticasone furoate, umeclidinium, vilanterol, or any of the excipients
* Unable to perform inspiratory flow or spirometry procedures
* Critically ill patients, or patients with rapidly deteriorating or life-threatening episodes of COPD or asthma including:

  * Patients in critical care unit, or transferred from critical care unit
  * Patients who are transferred to critical care after enrollment will be withdrawn from the study and continue to receive care according to institutional standard practice.
* Patients who initiate Bilevel Positive Airway Pressure (BiPAP) after hospitalization

  o Patients who use BiPAP at baseline (prior to COPD exacerbation) may be included if BiPAP settings remain consistent with pre-exacerbation settings. Patients will be withdrawn if BiPAP settings are changed after enrollment.
* Pregnant or lactating women or women of child-bearing potential (WOCBP). Women must meet the non-productive potential definition below to be eligible.

  * Non-reproductive potential is defined as
  * Pre-menopausal females with one of the following:
  * Documented tubal ligation
  * Documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal ligation
  * Hysterectomy
  * Documented Bilateral Oophorectomy
  * Postmenopausal defined as 12 months of spontaneous amenorrhea with an appropriate clinical profile (e.g., age appropriate, greater than 45 years, in the absence of hormone replacement therapy). In questionable cases for women less than 60 years of age, a blood sample with simultaneous follicle stimulating hormone and estradiol falling into the central laboratory's postmenopausal reference range is confirmatory. Females under 60 years of age, who are on HRT and whose menopausal status is in doubt, are required to use a highly effective method to avoid pregnancy if they wish to continue their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation of postmenopausal status prior to study enrolment. For most forms of HRT, at least 2 to 4 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, subjects can resume use of HRT during the study without use of a highly effective method to avoid pregnancy.

Primary outcomes:
measure: Number of PRN respiratory therapy drugs per day (PRN treatments with short acting bronchodilators via nebulization given by respiratory therapists).
timeFrame: 30 days
Secondary outcomes:
measure: Hospital Length of stay
timeFrame: 60 days
measure: Number of readmissions
timeFrame: 60 days
Other outcomes:
Locations:
city: Dallas
country: United States
facility: Baylor Scott & White Health Research Institute
state: Texas
Study officials:
affiliation: Baylor Scott and White Health
name: Mark W Millard, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Dunne PJ, Macintyre NR, Schmidt UH, Haas CF, Jones-Boggs Rye K, Kauffman GW, Hess DR. Respiratory care year in review 2011: long-term oxygen therapy, pulmonary rehabilitation, airway management, acute lung injury, education, and management. Respir Care. 2012 Apr;57(4):590-606. doi: 10.4187/respcare.01776.
citation: Chapin TW, Mann MA, Brown GL, Leitheiser TL, Anderson B, Leedahl DD. Effectiveness of Umeclidinium-Vilanterol for Protocolized Management of Chronic Obstructive Pulmonary Disease Exacerbation in Hospitalized Patients: A Sequential Period Analysis. Chronic Obstr Pulm Dis. 2018 Jan 24;5(1):38-45. doi: 10.15326/jcopdf.5.1.2017.0163.