Impact of Non-invasive Ventilation in Hypercapnic COPD

Overview

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.

Full Title of Study: “Impact of Non-invasive Ventilation on Biomarkers in Hypercapnic COPD”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: N/A
    • Intervention Model: Single Group Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: November 21, 2018

Interventions

  • Device: High-intensity non-invasive ventilation
    • Single night of high-intensity non-invasive ventilation

Arms, Groups and Cohorts

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

Clinical Trial Outcome Measures

Primary Measures

  • Paired difference in morning level of high sensitivity troponin between baseline and NIV nights
    • Time Frame: 1 day
    • Comparing morning levels of high sensitivity troponin between baseline and NIV nights

Secondary Measures

  • Paired difference in overnight increase in high sensitivity troponin between baseline and NIV night
    • Time Frame: 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
    • Time Frame: 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
    • Time Frame: 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
    • Time Frame: 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
    • Time Frame: 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
    • Time Frame: 1 day
    • Exhaled nitric oxide assay: Minimum 0, no maximumm with higher values worse.

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: 45 Years

Maximum Age: 75 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • University of California, San Diego
  • Provider of Information About this Clinical Study
    • Principal Investigator: Jeremy Orr, M.D., Assistant Clinical Professor – University of California, San Diego
  • Overall Official(s)
    • Jeremy E Orr, MD, Principal Investigator, UCSD

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