Impact of Non-invasive Ventilation in Hypercapnic COPD

Not Applicable

Terminated

• Conditions: Copd; Chronic Respiratory Failure; Hypercapnia; Chronic Obstructive Pulmonary Disease; Hypoventilation
• Interventions: Device: High-intensity non-invasive ventilation

• Registration Number: NCT03522805
• Lead Sponsor: University of California, San Diego

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2018-04-23
• Study First Submitted: 2018-05-01
• Study First Submitted QC: 2018-05-10
• Study First Posted: 2018-05-11
• Primary Completion: 2018-11-21
• Study Completion: 2018-11-21
• Status Verified: 2020-08
• Last Update Submitted: 2020-08-24
• Last Update Posted: 2020-08-27

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 6

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Non-invasive ventilation	High-intensity non-invasive ventilation	Subjects will undergo a baseline night with standard polysomnography, followed by a treatment night using non-invasive ventilation under polysomnography

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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 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 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.

Trial Locations

Locations (1)

University of California San Diego; 🇺🇸 San Diego, California, United States