NIV for COPD: Hospital to Home (H2H)

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

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:

1. Unplanned readmission rates (all complications)
2. Time to readmissions for admissions other than AECOPD.
3. Arterial blood gas/Venous blood gas (ABG/VBG): PaO2, PaCO2 and serum bicarbonate at Baseline, 6 and 12 months
4. 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)

Study Overview

• Status: Terminated
• Conditions: Pulmonary Disease, Chronic Obstructive; Noninvasive Ventilation
• Intervention / Treatment: Device: Noninvasive Ventilation

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Julia von Oppenfeld, BA; Phone Number: 23482 415-221-4810; Email: Julia.vonOppenfeld@va.gov

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94121
      • San Francisco VA Health Care System
      • Contact: Julia von Oppenfeld, BA
      • Principal Investigator: Kathleen Sarmiento, MD, MPH
      • Sub-Investigator: Mehrdad Arjomandi, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Admission for acute hypercapnic respiratory failure requiring mechanical ventilation or NIV
2. Resolution of acute respiratory failure reflected by normalization of pH and downgrade of clinical status to ward or floor status.
3. 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.
4. 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.
5. Able to consent without surrogate and complete all required study visits.

Exclusion Criteria:

1. 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.
2. BMI>35 kg/m2
3. Congestive heart failure (HFrEF, EF< 45%)
4. Other cause of chronic respiratory failure: Obesity hypoventilation syndrome, spinal cord injury (cervical or thoracic) neuromuscular disease, diaphragmatic paralysis, chest wall restrictive ventilatory defect
5. Lack of stable housing, homelessness, or unreliable electricity source in home environment.
6. Use of NIV at home within past three months
7. Failure to tolerate NIV during initial hospitalization
8. Unable or unwilling to comply with the protocol
9. Age <18 years
10. Inability to consent due to limited cognitive capacity
11. Pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Noninvasive Ventilation; 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; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: San Francisco Veterans Affairs Medical Center
• Collaborators: ResMed
• Investigators: Principal Investigator: Kathleen Sarmiento, MD, MPH, San Francisco VA Health Care System

Publications and helpful links

General Publications

• Budweiser S, Hitzl AP, Jorres RA, Heinemann F, Arzt M, Schroll S, Pfeifer M. Impact of noninvasive home ventilation on long-term survival in chronic hypercapnic COPD: a prospective observational study. Int J Clin Pract. 2007 Sep;61(9):1516-22. doi: 10.1111/j.1742-1241.2007.01427.x.
• Murphy PB, Rehal S, Arbane G, Bourke S, Calverley PMA, Crook AM, Dowson L, Duffy N, Gibson GJ, Hughes PD, Hurst JR, Lewis KE, Mukherjee R, Nickol A, Oscroft N, Patout M, Pepperell J, Smith I, Stradling JR, Wedzicha JA, Polkey MI, Elliott MW, Hart N. Effect of Home Noninvasive Ventilation With Oxygen Therapy vs Oxygen Therapy Alone on Hospital Readmission or Death After an Acute COPD Exacerbation: A Randomized Clinical Trial. JAMA. 2017 Jun 6;317(21):2177-2186. doi: 10.1001/jama.2017.4451.
• De Backer L, Vos W, Dieriks B, Daems D, Verhulst S, Vinchurkar S, Ides K, De Backer J, Germonpre P, De Backer W. The effects of long-term noninvasive ventilation in hypercapnic COPD patients: a randomized controlled pilot study. Int J Chron Obstruct Pulmon Dis. 2011;6:615-24. doi: 10.2147/COPD.S22823. Epub 2011 Nov 18.
• Storre JH, Matrosovich E, Ekkernkamp E, Walker DJ, Schmoor C, Dreher M, Windisch W. Home mechanical ventilation for COPD: high-intensity versus target volume noninvasive ventilation. Respir Care. 2014 Sep;59(9):1389-97. doi: 10.4187/respcare.02941. Epub 2014 Jul 29.
• Oscroft NS, Chadwick R, Davies MG, Quinnell TG, Smith IE. Volume assured versus pressure preset non-invasive ventilation for compensated ventilatory failure in COPD. Respir Med. 2014 Oct;108(10):1508-15. doi: 10.1016/j.rmed.2014.07.010. Epub 2014 Jul 23.
• Mansfield D, Naughton MT. Effects of continuous positive airway pressure on lung function in patients with chronic obstructive pulmonary disease and sleep disordered breathing. Respirology. 1999 Dec;4(4):365-70. doi: 10.1046/j.1440-1843.1999.00206.x.
• Gunduz C, Basoglu OK, Tasbakan MS. Prevalence of overlap syndrome in chronic obstructive pulmonary disease patients without sleep apnea symptoms. Clin Respir J. 2018 Jan;12(1):105-112. doi: 10.1111/crj.12493. Epub 2016 Jun 6.

Study record dates

Study Major Dates

• Study Start (Actual): May 9, 2019
• Primary Completion (Actual): April 1, 2024
• Study Completion (Actual): April 1, 2024

Study Registration Dates

• First Submitted: October 7, 2019
• First Submitted That Met QC Criteria: May 28, 2020
• First Posted (Actual): June 4, 2020

Study Record Updates

• Last Update Posted (Actual): April 25, 2024
• Last Update Submitted That Met QC Criteria: April 23, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: COPD; NIV; Respiratory failure; BIPAP
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Disease Attributes; Lung Diseases, Obstructive; Chronic Disease; Lung Diseases; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: 18-25750

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No