Clinical trial NCT04413643: NIV for COPD: Hospital to Home
Official title: Noninvasive Ventilation for Chronic Obstructive Pulmonary Disease: Hospital to Home Pilot
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Pulmonary Disease, Chronic Obstructive
Noninvasive Ventilation
Keywords: COPD
BIPAP
NIV
Respiratory failure
Lead sponsor: San Francisco Veterans Affairs Medical Center
Sponsor class: FED
Collaborators: name: ResMed
First posted: 2020-06-04
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: This is a feasibility trial intended to inform a larger clinical trial based on outcomes data collected.
Primary purpose: TREATMENT

Brief summary: 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)

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.

Eligibility criteria: 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

Primary outcomes:
measure: Event-free survival
timeFrame: 1 year
Secondary outcomes:
measure: Unplanned readmission rates (all complications)
timeFrame: 1 year
measure: Time to readmissions for admissions other than AECOPD
timeFrame: 1 year
measure: Change in PaO2 levels from baseline to 12mo
timeFrame: 1 year
measure: Change PaCO2 levels from baseline to 12mo
timeFrame: 1 year
measure: Change in serum bicarbonate levels from baseline to 12mo
timeFrame: 1 year
measure: Spirometry/Lung Function
timeFrame: 1 year
measure: Spirometry/Lung Function
timeFrame: 1 year
measure: Spirometry/Lung Function
timeFrame: 1 year
measure: Spirometry/Lung Function
timeFrame: 1 year
measure: Spirometry/Lung Function
timeFrame: 1 year
measure: Spirometry/Lung Function
timeFrame: 1 year
measure: Spirometry/Lung Function
timeFrame: 1 year
measure: Spirometry/Lung Function
timeFrame: 1 year
measure: Spirometry/Lung Function
timeFrame: 1 year
measure: Spirometry/Lung Function
timeFrame: 1 year
measure: Spirometry/Lung Function
timeFrame: 1 year
measure: Spirometry/Lung Function
timeFrame: 1 year
measure: Spirometry/Lung Function
timeFrame: 1 year
measure: Spirometry/Lung Function
timeFrame: 1 year
measure: 6 minute walk test
timeFrame: 1 year
measure: St. Georges Respiratory Questionnaire
timeFrame: 1 year
measure: Adherence/Compliance with NIV
timeFrame: 1 year
measure: Adherence/Compliance with NIV
timeFrame: 1 year
measure: Adherence/Compliance with NIV
timeFrame: 1 year
measure: Adherence/Compliance with NIV
timeFrame: 1 year
measure: Sleep assessed by type 3 portable monitors and transcutaneous capnography
timeFrame: 1 year
measure: Epworth Sleepiness Scale assessment for daytime sleepiness
timeFrame: 1 year
measure: Insomnia Severity Index assessment for difficulty falling asleep and staying asleep.
timeFrame: 1 year
measure: Pittsburgh sleep quality index (PSQI) questionnaire to measure sleep disturbance and sleep habits
timeFrame: 1 year
measure: Functional Outcomes of Sleep Questionnaire (short form) to measure functional status resulting from sleepiness and is a measure of sleep-related HRQoL.
timeFrame: 1 year
measure: Utilization of healthcare services (visits to outpatient clinics and emergency services, and number of inpatient admissions)
timeFrame: 1 year
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: San Francisco VA Health Care System
state: California
Study officials:
affiliation: San Francisco VA Health Care System
name: Kathleen Sarmiento, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.