Impact of Non-invasive Ventilation in Hypercapnic COPD

NCT03522805 | Terminated

• 1 other identifier: 161873
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

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.

Conditions

Copd; Chronic Obstructive Pulmonary Disease; Hypercapnia; Chronic Respiratory Failure; Hypoventilation

Keywords

copd; lung; non-invasive ventilation; hypercapnia; hypoventilation

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Paired difference in overnight increase in high sensitivity troponin between baseline and NIV night

  1 day

• Paired difference in sleep quality by Richards-Campbell Sleep Questionnaire between baseline and NIV night

  1 day

• Paired difference in sleep quality by arousal index between baseline and NIV night

  1 day

• Paired 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

  1 day

Study Arms (1)

Non-invasive ventilation

EXPERIMENTAL

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

Interventions

High-intensity non-invasive ventilation DEVICE

Single night of high-intensity non-invasive ventilation

Non-invasive ventilation

Eligibility Criteria

• Age: 45 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of California, San Diego: lead

Study Sites (1)

University of California San Diego

San Diego, California, 92037, United States

Location

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive; Hypercapnia; Hypoventilation

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms, Respiratory; Signs and Symptoms; Respiratory Insufficiency; Respiration Disorders

Study Officials

• Jeremy E Orr, MD

  UCSD

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Clinical Professor

Study Record Dates

• First Submitted: May 1, 2018
• First Posted: May 11, 2018
• Study Start: April 23, 2018
• Primary Completion: November 21, 2018
• Study Completion: November 21, 2018
• Last Updated: August 27, 2020

Record last verified: 2020-08

Locations

US (1)