Impact of Non-invasive Ventilation in Hypercapnic COPD

Sponsor

University of California, San Diego (Other)

Overall Status

Terminated

CT.gov ID

NCT03522805

Collaborator

(none)

Enrollment

Location

Arm

Actual Duration (Months)

0.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Chronic obstructive pulmonary disease (COPD) is a highly prevalent condition worldwide and is a cause of substantial morbidity and mortality. Unfortunately, few therapies have been shown to improve survival. The importance of systemic effects and co-morbidities in COPD has garnered attention based on the observation that many patients with COPD die from causes other than respiratory failure, including a large proportion from cardiovascular causes. Recently, two high profile randomized trials have shown substantial improvements in morbidity and mortality with use of nocturnal non-invasive ventilation (NIV) in COPD patients with hypercapnia. Although the mechanisms by which NIV improves outcomes remain unclear, the important benefits of NIV might be cardiovascular via a number of mechanisms. In contrast to prior trials of NIV in COPD that did not show substantial benefit, a distinguishing feature of these encouraging recent NIV clinical trials was a prominent reduction of hypercapnia, which might be a maker or mediator of effective therapy. Alternatively, improvements might be best achieved by targeting a different physiological measure. Additional mechanistic data are therefore needed to inform future trials and achieve maximal benefit of NIV. Recent work in cardiovascular biomarkers has identified high-sensitivity troponin to have substantial ability to determine cardiovascular stress in a variety of conditions - even with only small changes. In COPD, a number of observational studies have shown that high-sensitivity troponin increases with worsening disease severity, and that levels increase overnight during sleep. This biomarker therefore presents a promising means to study causal pathways regarding the effect of NIV in patients with COPD. With this background, the investigator's overall goals are: 1) To determine whether the beneficial effect of non-invasive ventilation might be due to a reduction in cardiovascular stress, using established cardiovascular biomarkers, and 2) To define whether a reduction in PaCO2 (or alternative mechanism) is associated with such an effect.

Condition or Disease	Intervention/Treatment	Phase
Copd Chronic Obstructive Pulmonary Disease Hypercapnia Chronic Respiratory Failure Hypoventilation	Device: High-intensity non-invasive ventilation	N/A

Study Design

Study Type:

Interventional

Actual Enrollment :

6 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Impact of Non-invasive Ventilation on Biomarkers in Hypercapnic COPD

Actual Study Start Date :

Apr 23, 2018

Actual Primary Completion Date :

Nov 21, 2018

Actual Study Completion Date :

Nov 21, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Non-invasive ventilation Subjects will undergo a baseline night with standard polysomnography, followed by a treatment night using non-invasive ventilation under polysomnography	Device: High-intensity non-invasive ventilation Single night of high-intensity non-invasive ventilation

Arm

Intervention/Treatment

Experimental: Non-invasive ventilation

Subjects will undergo a baseline night with standard polysomnography, followed by a treatment night using non-invasive ventilation under polysomnography

Device: High-intensity non-invasive ventilation

Single night of high-intensity non-invasive ventilation

Outcome Measures

Primary Outcome Measures

Paired difference in morning level of high sensitivity troponin between baseline and NIV nights [1 day]
Comparing morning levels of high sensitivity troponin between baseline and NIV nights

Secondary Outcome Measures

Paired difference in overnight increase in high sensitivity troponin between baseline and NIV night [1 day]
Troponin assay: Minimum 0, no maximum, with higher values worse.
Paired difference in sleep quality by Richards-Campbell Sleep Questionnaire between baseline and NIV night [1 day]
Questionnaire: 5 questions, 0 to 100 on visual analog scale, with higher scores indicating better sleep. Total score reported as mean of 5 components.
Paired difference in sleep quality by arousal index between baseline and NIV night [1 day]
Arousal index: Index reported as events/hour. Minimum 0, no maximum, with higher scores indicating worse sleep.
Paired difference in heart rate variability during sleep between baseline and NIV night [1 day]
Comparing difference in heart rate variability during sleep between baseline and NIV night
Paired difference between Morning psychomotor vigilance testing score between baseline and NIV night [1 day]
Psychomotor vigilance score: Reported as number of lapses. Minimum 0, no maximum, with higher values worse.
Paired difference in morning exhaled nitric oxide level between baseline and NIV night [1 day]
Exhaled nitric oxide assay: Minimum 0, no maximumm with higher values worse.

Eligibility Criteria

Criteria

Ages Eligible for Study:

45 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Subjects with previously diagnosed severe COPD (FEV1 <50% predicted) and daytime hypercapnia (PaCO2 or TcCO2 > 45 mmHg)

Exclusion Criteria:

Lung disease besides COPD (e.g., pulmonary fibrosis, bronchiectasis, pulmonary arterial hypertension) other than well controlled asthma
Unrevascularized coronary artery disease, angina, prior heart attack or stroke, congestive heart failure
Uncontrolled hypertension (SBP >160, DBP >95)
Unwilling or unable to withhold CPAP during polysomnography
Presence of tracheostomy
Hospitalization within the past 90 days
Prior peptic ulcer disease, esophageal varicies, or gastrointestinal bleeding (< 5 years)
Prior gastric bypass surgery
Anticoagulant use (other than aspirin) or bleeding diathesis (only for esophageal catheter placement)
Chronic liver disease or end-stage kidney disease
Allergy to any of the study medications
Regular use of medications known to affect control of breathing (opioids, benzodiazepines, theophylline)
Insomnia or circadian rhythm disorder
Active illicit substance use or >3 oz nightly alcohol use
Psychiatric disease, other than controlled depression
Pregnancy
Prisoners
Cognitive impairment, unable to provide consent, or unable to carry out research procedures