NIV for COPD: Hospital to Home

Study Overview
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Brief Summary
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This is a pilot study to evaluate the impact of providing patients admitted with acute exacerbations of COPD (AECOPD) with non-invasive ventilation (NIV)home devices prior to discharge on hospital readmission rates and other secondary outcomes. Aim 1 To test whether continuation of NIV at home after being initiated during hospitalization for AECOPD improves subsequent admission-free survival in patients with chronic hypercapnic respiratory failure secondary to COPD Hypothesis 1: The use of targeted NIV during hospitalization with continuation upon discharge to home will improve one-year all-cause mortality as compared to published mortality in the current literature. Hypothesis 2: The use of targeted NIV during hospitalization with continuation upon discharge to home will reduce readmission rates for AECOPD within-institution historical data. Aim 2 To evaluate the feasibility of a larger multisite randomized controlled trial in veterans using inclusion and exclusion criteria specified in this pilot. Outcomes Primary: Event-free survival (re-hospitalization for AECOPD, time to readmission for AECOPD, and all-cause mortality) Secondary: Unplanned readmission rates (all complications) Time to readmissions for admissions other than AECOPD. Arterial blood gas/Venous blood gas (ABG/VBG): PaO2, PaCO2 and serum bicarbonate at Baseline, 6 and 12 months Pulmonary function (handheld spirometer or in-laboratory based on specific institution resources) at Baseline, 6, and 12 months 5.6 minute walk test at Baseline, 6,and 12 months 6.Health related quality of life (HRQOL) measured by the St. Georges respiratory questionnaires (SGRQ) at Baseline, 1,3,6,9 and 12 months 7.Adherence to NIV at Week 1-2, Months 1,3,6,9 and 12 8.Sleep assessed by type 3 portable monitors 9.Sleep assessed by questionnaires: Insomnia severity index (ISI), Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index (PSQI), Functional Outcomes of Sleep Short Form (FOSQ-10) at Baseline, 1,3,6,9 and 12 months 11.Utilization of healthcare services (number of visits to outpatient clinics and emergency services, number of inpatient admissions)

Detailed Description
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Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide, with the economic and social burden of disease anticipated to increase annually. Acute exacerbations of COPD (AECOPD) are associated with significant in-hospital mortality (6-8%), high readmission rates (60-80%), and even more dramatic 1-year mortality (23-49%). The use of non-invasive ventilation (NIV) has been extensively evaluated in both patients with stable disease in the home setting and in AECOPD during hospitalization. It is widely accepted that NIV used during AECOPD in the inpatient setting reduces rates of endotracheal intubation, as well as length of ICU and hospital stay. Long-term use of NIV, particularly at higher pressures, in the home setting in COPD patients with evidence of chronic compensated respiratory acidosis (PaCO2 >45mmHg) decreases elevated PaCo2 and serum bicarbonate levels, improves pulmonary function, and improves quality of life. Little is known about whether patients initiated on NIV during an AECOPD and subsequently transitioned to long-term home NIV on discharge demonstrate reduced AECOPD rates, readmission rates, or differences in morbidity and mortality. The few existing randomized trials aimed at this patient population suffer from criticisms of lack of power, varying degrees of patient symptoms, conflicting results, and inconsistent approaches in NIV strategies. Nonetheless, this is an important population to address, as AECOPD frequently leads to accelerated loss of lung function (pre-AECOPD function not recovered), decreased quality of life (QOL), more frequent exacerbations, and higher overall mortality. If NIV can minimize the loss of lung function during the transition period following AECOPD, QOL, physical activity tolerance, readmission rates and overall mortality may improve. Economic analyses of the use of NIV in patients with AECOPD transitioning from the inpatient to home setting are also sparse, but of high value as healthcare transitions toward bundled payments and penalties for readmissions. This pilot study seeks to better inform the literature on the role of NIV initiated during inpatient AECOPD and continued long-term following discharge home in patients with chronic hypercapnic respiratory failure due to COPD. The investigators hypothesize that the use of NIV during acute inpatient treatment of AECOPD followed by continuation of NIV therapy long-term at home will improve admission free survival, improve quality of life, reduce 1-year exacerbation rates, and reduce 30d readmissions. This is a prospective 1-year interventional pilot study that will occur at 4 Veterans Affairs (VA) hospitals (Sacramento, Durham, Pittsburgh, and San Francisco). The total enrollment goal across all sites is 50. Total study period expected includes an enrollment period of approximately 10-12 months and follow-up period of 12 months for a total study duration of approximately 2 years.

Official Title
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Noninvasive Ventilation for Chronic Obstructive Pulmonary Disease: Hospital to Home Pilot

Conditions
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Noninvasive Ventilation, Pulmonary Disease, Chronic Obstructive

Intervention / Treatment
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* Device: Noninvasive Ventilation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Admission for acute hypercapnic respiratory failure requiring mechanical ventilation or NIV Resolution of acute respiratory failure reflected by normalization of pH and downgrade of clinical status to ward or floor status. Severe COPD defined by GOLD stage 3 (FEV1 30-50%) or 4 (FEV1 < 30%) OR GOLD C or D. Pulmonary function tests (PFTs) done within 3 years preceding admission are acceptable to document an obstructive ventilatory defect and decrease diffusion capacity consistent with emphysema and COPD. If no PFTs are available, bedside spirometry will be performed to confirm COPD. Chronic compensated respiratory acidosis based on PaCO2 >52 adjusted for pH 7.40, on pre-admission laboratory values or after resolution of acute respiratory failure. Able to consent without surrogate and complete all required study visits. Exclusion Criteria: Moderate or severe obstructive sleep apnea (OSA), apnea-hypopnea index (AHI) >15/h. Sleep testing done within the prior 3 years with no increase in body mass index (BMI) >2kg/m2 or major change in cardiopulmonary conditions (new reduced ejection heart failure [HFrEF], atrial fibrillation [AFib], opioid use with morphine dose equivalent (MDDE) >120mg, or cardiothoracic surgery for lung resection or coronary artery bypass grafting) will be accepted for AHI severity. BMI>35 kg/m2 Congestive heart failure (HFrEF, EF< 45%) Other cause of chronic respiratory failure: Obesity hypoventilation syndrome, spinal cord injury (cervical or thoracic) neuromuscular disease, diaphragmatic paralysis, chest wall restrictive ventilatory defect Lack of stable housing, homelessness, or unreliable electricity source in home environment. Use of NIV at home within past three months Failure to tolerate NIV during initial hospitalization Unable or unwilling to comply with the protocol Age <18 years Inability to consent due to limited cognitive capacity Pregnancy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: This is a feasibility trial intended to inform a larger clinical trial based on outcomes data collected.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Noninvasive Ventilation<br>Subjects will be introduced to NIV and educated on sleep disordered breathing. NIV will be initiated during hospitalization following resolution of acute respiratory failure. NIV settings will be based on inspiratory and expiratory positive airway pressures (IPAP, EPAP), rates, and tidal volumes tolerated during the acute phase of treatment. Initial settings will be set with goals of tolerance and acceptance of therapy. Minimum pressure difference between IPAP and EPAP settings will be 5cmH20. Volume assured pressure support mode with a target tidal volume (Vt) of 8ml/kg ideal body weight will be used. Final device settings and patient parameters will be documented after 10 minutes of acclimation to the device. Data from the device will be reviewed the following day. Tolerance, mask comfort, and acceptance of therapy will be assessed. Changes to settings, mask interface, or other comfort features will be performed at this initial reassessment period. | Device: Noninvasive Ventilation<br>* The use of non-invasive ventilation (NIV) has been extensively evaluated in both patients with stable disease in the home setting and in AECOPD during hospitalization. It is widely accepted that NIV used during AECOPD in the inpatient setting reduces rates of endotracheal intubation, as well as length of ICU and hospital stay. Long-term use of NIV, particularly at higher pressures, in the home setting in COPD patients with evidence of chronic compensated respiratory acidosis (PaCO2 >45mmHg) decreases elevated PaCo2 and serum bicarbonate levels, improves pulmonary function, and improves quality of life. Little is known about whether patients initiated on NIV during an AECOPD and subsequently transitioned to long-term home NIV on discharge demonstrate reduced AECOPD rates, readmission rates, or differences in morbidity and mortality.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Event-free survival | Re-hospitalization for AECOPD, time to readmission for AECOPD, and all-cause mortality | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Unplanned readmission rates (all complications) |  | 1 year | 
| Time to readmissions for admissions other than AECOPD |  | 1 year | 
| Change in PaO2 levels from baseline to 12mo | PaO2 will be measured at baseline, 6 and 12 months and evaluated for significant increase (PaO2) or decrease (PaCO2, serum bicarbonate) | 1 year | 
| Change PaCO2 levels from baseline to 12mo | PaCO2 will be measured at baseline, 6 and 12 months and evaluated for significant increase (PaO2) or decrease (PaCO2, serum bicarbonate) | 1 year | 
| Change in serum bicarbonate levels from baseline to 12mo | Serum bicarbonate will be measured at baseline, 6 and 12 months and evaluated for significant increase (PaO2) or decrease (PaCO2, serum bicarbonate) | 1 year | 
| Spirometry/Lung Function | Forced expiratory volume (FEV1) measured at baseline, 6mo and 12mo | 1 year | 
| Spirometry/Lung Function | Absolute Forced Expiratory Volume (L) measured at baseline, 6mo and 12mo | 1 year | 
| Spirometry/Lung Function | % Forced Expiratory Volume measured at baseline, 6mo and 12mo | 1 year | 
| Spirometry/Lung Function | Forced Vital Capacity (FVC) measured at baseline, 6mo and 12mo | 1 year | 
| Spirometry/Lung Function | Absolute Forced Vital Capacity (L) measured at baseline, 6mo and 12mo | 1 year | 
| Spirometry/Lung Function | % Forced Vital Capacity measured at baseline, 6mo and 12mo | 1 year | 
| Spirometry/Lung Function | Total Lung Capacity (TLC) measured at baseline, 6mo and 12mo | 1 year | 
| Spirometry/Lung Function | Absolute Total Lung Capacity (L) measured at baseline, 6mo and 12mo | 1 year | 
| Spirometry/Lung Function | % Total Lung Capacity measured at baseline, 6mo and 12mo | 1 year | 
| Spirometry/Lung Function | Residual Volume (RV) measured at baseline, 6mo and 12mo | 1 year | 
| Spirometry/Lung Function | Absolute Residual Volume (L) measured at baseline, 6mo and 12mo | 1 year | 
| Spirometry/Lung Function | % Residual Volume measured at baseline, 6mo and 12mo | 1 year | 
| Spirometry/Lung Function | FEV1/FVC% measured at baseline, 6mo and 12mo | 1 year | 
| Spirometry/Lung Function | Diffusion Capacity (DLCO) measured at baseline, 6mo and 12mo | 1 year | 
| 6 minute walk test | At baseline, 6 mo and 12 mo | 1 year | 
| St. Georges Respiratory Questionnaire | 50-item, 3 component questionnaire. Scores range from 0-100 with a higher score indicating more limitations. Measures the impact of breathing symptoms on quality of life. Administered at baseline, 1, 3, 6, 9 and 12 months | 1 year | 
| Adherence/Compliance with NIV | Standard total days used since therapy initiation (day 0). Measured at week 1-2, months 1, 3, 6, 9 and 12. Data will be obtained through remote review of wireless data transmitted from each device. | 1 year | 
| Adherence/Compliance with NIV | Percent days with use >4h/d. Measured at week 1-2, months 1, 3, 6, 9 and 12. Data will be obtained through remote review of wireless data transmitted from each device. | 1 year | 
| Adherence/Compliance with NIV | Average time used on days used. Measured at week 1-2, months 1, 3, 6, 9 and 12. Data will be obtained through remote review of wireless data transmitted from each device. | 1 year | 
| Adherence/Compliance with NIV | Average time used on all days. Measured at week 1-2, months 1, 3, 6, 9 and 12. Data will be obtained through remote review of wireless data transmitted from each device. | 1 year | 
| Sleep assessed by type 3 portable monitors and transcutaneous capnography | At baseline | 1 year | 
| Epworth Sleepiness Scale assessment for daytime sleepiness | 8 question survey that measures the propensity of falling asleep in different situations. Composite score reported, with a range from 0-24, the higher the score indicating a greater propensity for falling asleep. Administered at baseline, 1, 3, 6, 9 and 12 months | 1 year | 
| Insomnia Severity Index assessment for difficulty falling asleep and staying asleep. | 7-item survey that uses a likert scale. Measures the nature, severity, and impact of insomnia in adults. Composite score reported (0-28), with a higher score indicating a greater severity of insomnia. Administered at baseline, 1, 3, 6, 9 and 12 months | 1 year | 
| Pittsburgh sleep quality index (PSQI) questionnaire to measure sleep disturbance and sleep habits | 19 item questionnaire with 7 domains (sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medications, and daytime dysfunction), using a likert scale. Measures sleep disturbance and usual sleep habits during the prior month only. A global socre of 0-21 is used, with a score >5 indicating poor sleep quality. The higher the score the poorer the sleep quality. Administered at baseline, 1, 3, 6, 9 and 12 months | 1 year | 
| Functional Outcomes of Sleep Questionnaire (short form) to measure functional status resulting from sleepiness and is a measure of sleep-related HRQoL. | 10 item questionnaire with 5 subscales. Subscale scores are averaged to obtain a total score ranging from 5-20, with a higher score indicating better functional status. Administered at baseline, 1, 3, 6, 9 and 12 months | 1 year | 
| Utilization of healthcare services (visits to outpatient clinics and emergency services, and number of inpatient admissions) | Visits (both outpatient and inpatient) will be identified based on VA-specific stop codes which define what type of visit occurred (specialty, date, and provider type). | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COPD, BIPAP, NIV, Respiratory failure