A Multi-center, Prospective, Randomized, Controlled Trial of Endobronchial Valve (EBV)
Therapy vs. Standard of Care (SoC) in Heterogeneous Emphysema.

Patients with severe emphysema suffer from severe dyspnea and a poor quality of
life, with no current effective medical treatment. Only for a very small,
highly selective group of COPD patients, very invasive surgical procedures like
lung volume reduction surgery (LVRS) or lungtransplantation are available.
Minimally invasive bronchoscopic lung volume reduction (BLVR) techniques
through the implantation of one-way valves have now been established as a means
of treating the hyperinflation of emphysema for a group of selected
patients.clinical evidence indicates that by achieving lobar occlusion in the
absence of collateral ventilation, significant lung volume reduction can be
obtained with associated good clinical responses. The Chartis Pulmonary
Assessment System which assesses collateral ventilation has shown 75% accuracy
in predicting response.

To compare the clinical outcomes of Endoscopic Lung Volume Reduction (ELVR)
using the Pulmonx Zephyr Endobronchial Valve (EBV) vs. Standard of Care (SoC)
in the treatment of heterogeneous emphysema subject in a controlled trial
design setting.

This is a prospective, randomized, controlled, two-armed multi-center trial.
Subjects in the SoC group will be offered to receive EBVs after completing the
6 months follow up, or before 6 months if the clinical condition of the
individual patient deteriorates and valve placement is required as per the
decision of the treating physician.

The Pulmonx Zephyr Endobronchial Valve (EBV) is an implantable bronchial valve
intended to decrease volume in targeted regions of the lung. It is indicated
for the treatment of patients with hyperinflation associated with severe
heterogeneous emphysema in regions of the lung that have little or no
collateral ventilation as assessed by the Chartis System.

The patients that will be included in the study will have to come to our
outpatient clinic, perform pulmonary function testing, a 6 min walking test,
HRCT scanning, thoracic x-ray, fill in questionnaires and testing of blood
samples and arterial blood gas. For the actual treatment with bronchoscopy
under general anesthesia the patients will stay 6 nights in our hospital. For
the follow-up, the patients will visit the hospital (7x or 3x), which will
include 1 CT scan and pulmonary function tests, questionnaires and exercise
testing (6MWT). The included patients will have to put large effort in the
study, but is in balance with the expected outcome and very limited compared
'alternative' treatments like highly invasive surgery: Lung volume reduction
surgery or Lung transplantation. All included patients have a severe limitation
of their activities of daily living. With the development and validation of the
use of the lung volume reduction treatment with the placement of valves, does
it seem possible to give relieve of shortness of breath and improvement in
exercise performance. Furthermore, this technique can be used as a 'bridge' to
lung transplantation in future, or will be the only possible therapeutic tool
available by them. The risks are not bigger than the risks any individual has
for the investigations described. The treatment with the valves and inducing
the significant volume reduction the major risks involved are: Pneumothorax (1
in 4 patients) for which chest drainage is required, transient (1-3 days) chest
pain (1 in 2 patients), transient (1-7 days) and dyspnea (1 in 4 patients).