Impact of Non-invasive Ventilation in Hypercapnic COPD

Impact of Non-invasive Ventilation on Biomarkers in Hypercapnic COPD

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.

Study Overview

• Status: Terminated
• Conditions: Chronic Obstructive Pulmonary Disease; Copd; Chronic Respiratory Failure; Hypoventilation; Hypercapnia
• Intervention / Treatment: Device: High-intensity non-invasive ventilation

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

Contacts and Locations

Study Locations

• United States
  • California
    • San Diego, California, United States, 92037
      • University of California San Diego

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 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: 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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: University of California, San Diego
• Investigators: Principal Investigator: Jeremy E Orr, MD, UCSD

Study record dates

Study Major Dates

• Study Start (Actual): April 23, 2018
• Primary Completion (Actual): November 21, 2018
• Study Completion (Actual): November 21, 2018

Study Registration Dates

• First Submitted: May 1, 2018
• First Submitted That Met QC Criteria: May 10, 2018
• First Posted (Actual): May 11, 2018

Study Record Updates

• Last Update Posted (Actual): August 27, 2020
• Last Update Submitted That Met QC Criteria: August 24, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: lung; non-invasive ventilation; copd; hypercapnia; hypoventilation
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Signs and Symptoms, Respiratory; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Respiratory Insufficiency; Hypoventilation; Hypercapnia
• Other Study ID Numbers: 161873

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No