Clinical trial NCT06181357: Trial Evaluating the Rate of Pneumothorax in Severe Emphysema Secondary to Endoscopic Volume Reduction With Two-stage ZEPHYR® Valves Versus Endoscopic Volume Reduction With One-stage ZEPHYR® Valves
Official title: Randomized Trial Evaluating the Rate of Pneumothorax in Severe Emphysema Secondary to Endoscopic Volume Reduction With Two-stage ZEPHYR® Valves Versus Endoscopic Volume Reduction With One-stage ZEPHYR® Valves
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: COPD
Keywords: Endobronchial Zephyr® valves
Endoscopic lung volume reduction
Pneumothorax
Emphysema
COPD
Lead sponsor: University Hospital, Limoges
Sponsor class: OTHER
First posted: 2023-12-26
Enrollment: 244
Sex: ALL
Minimum age (years): 35
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Chronic obstructive pulmonary disease (COPD) affects 3.5 million people and is the third leading cause of death worldwide. Emphysema involves air retention in the lungs and is ultimately responsible for a major deterioration in the quality of life. Available drug treatments have moderate efficacy whereas surgical lung volume reduction can improve exercise capacity when offered to a very selected population but at the cost of significant morbidity and mortality.

Endoscopic Lung Volume reduction with ZEPHYR® valves improves respiratory function at rest, exercise tolerance and quality of life in patients with little or no interlobar collateral ventilation.

If this technique has therefore proven its effectiveness, it is not devoid of complications and is notably responsible for pneumothorax in 27% of cases. The management of this complication is clearly codified, ranging from patient monitoring to the removal of one or more valves. It is therefore a subject of major concern for multiple reasons: high incidence, lengthening of hospital stay, increase in the overall cost of care, potential loss of benefit for the patient in the event of permanent withdrawal. valves and above all a potentially fatal event.

A new strategy for implanting ZEPHYR® valves in two stages has been developed in Limoges University Hospital. This innovative algorithm has been evaluated in several non-comparative single or multicenter studies. In those studies, pneumothorax' rate secondary to lung volume reduction with endobronchial valves is rated between 4.5 and 12%. The efficacy of the treatment appears to be comparable with the data found in the trials evaluating in which the entire lobe was treated in one procedure. Moreover, despite two procedures, there does not seem to be any increased risk of occurrence of other complications. Finally, the systematic scheduling of a thoracic computed tomography between the two procedures showed that 26.6% of patients presented a reduction in volume greater than 350mL despite incomplete treatment.

These data seem promising but no direct comparison with standard one-step treatment has ever been conducted so far.

Detailed description: The Zephyr® valve was first implanted in 2001. Since then, 5 important studies have proven a clinical superiority compared to the existing standard of care. Bronchoscopic lung-volume reduction with the use of one-way endobronchial valves is a potential treatment for patients with severe emphysema. Loss of lung elastic recoil leads to airflow obstruction, gas trapping, and increased operating lung volumes. Lung volume reduction surgery (LVRS), resection of the most affected of the lung, has been clearly shown to improve outcomes in selected patient groups. The surgical intervention is, however, associated with significant morbidity and an early mortality rate of about 5%. Therefore, there is considerable interest in developing novel treatment approaches that can reduce lung volume and gas trapping, either more safely than LVRS or in patients for whom LVRS is not an option.

In the present study, 244 patients will be randomized. After the selection process, they will all be hospitalized in order to undergo an endoscopic lung volume reduction with Zephyr® valve under general anesthesia. Half of them, the experimental group, will be treated according to Limoges' treatment algorithm (2 stages). For the other half, the control group, the entire lobe will be treated during one procedure will. Both groups will receive the standard of care treatments, according to the Global initiative for chronic Obstructive Lung Disease recommendations (GOLD).

Both groups will be followed for one year:

* All the patients will undergo a thorax CT scan 45 days after implanting the last valve. Three follow-up consultations are planned at 45 days, 6, and 12 months. During these consultations, each patient will complete a Saint-George Respiratory Questionnaire (SGRQ) Test, a plethysmography and a 6-minutes walking test.
* Patients randomized in the experimental group will undergo a plethysmography and a thorax CT scan one day before the second procedure.

Eligibility criteria: Inclusion Criteria:

Patient able to give informed consent and participate in the study

* Age ≥ 35 years old and ≤ 80 years old at the time of signing the consent
* Emphysema (homogeneous or heterogeneous) on a recent CT scan (\< 6 months). Heterogeneous emphysema defined by a difference of at least 15% destruction (threshold 910HU) between two adjacent lobes.
* Destruction ≥ 50% (threshold 910 HU) of the target lobe on the chest scanner
* Smoking quit for 3 months
* Dyspnea ≥ 2 according to the modified Medical Research Council (mMRC) questionnaire)
* Post-bronchodilator FEV between 15 and 50% theoretical
* Post-bronchodilator total lung capacity ≥ 100% theoretical and post-bronchodilator residual volume ≥ 175% theoretical
* Distance traveled during the TM6M ≥ 100m
* Member of or beneficiary of a social security scheme

Exclusion Criteria:

* Asthma considered as main diagnosis
* Recurrent exacerbations: (\>3 over the last year or 2 requiring hospitalization)
* Myocardial infarction or stroke in the 6 months prior to inclusion
* Symptoms of heart failure in the 6 months prior to inclusion
* Chest CT abnormalities: giant bulla (occupying more than a third of the pulmonary field), paraseptal emphysema, pulmonary nodule greater than 0.8cm (not applicable pulmonary nodules known for more than a year and stable), fibrosing interstitial pneumonitis, dilated bronchi
* Pulmonary tomoscintigraphy:

  * Patients for whom the least perfused lobe is not the one with the highest emphysema destruction score
  * Patients with homogeneous emphysema for whom the perfusion delta (difference in perfusion between the ipsilateral lung and the treated lobe) is less than 10%
* Arterial blood gas analysis in ambient air: Hypoxemia in ambient air (PaO2 \< 45 mmHg). Hypercapnia (PaCO2 \> 55 mmHg)
* Echocardiography:

  * Left Ventricular Ejection Function \< 45%
  * Systolic pulmonary arterial pressure \> 45 mmHg
* History of pneumonectomy, lung surgery homolateral to the lobe targeted for endoscopic lung volume reduction
* History of pneumothorax homolateral to the lobe targeted for endoscopic lung volume reduction
* History of endoscopic volume reduction
* Oral corticosteroid therapy \> 20 mg/day within the 4 weeks preceding inclusion
* Symptomatic bronchial dilatations, bronchial colonization with pseudomonas aeruginosa, multi-resistant bacteria or aspergillus origin
* Metastatic cancer undergoing treatment or whose treatments ended less than 5 years ago
* Pregnant or breastfeeding women
* Nickel allergy
* Patient under guardianship, curatorship or under judicial protection
* Participation in another interventional clinical research
* Any other condition which, in the opinion of the investigator, could interfere with the objective of the study or would cause the subject's participation in the study to be suboptimal, in particular (non-exhaustive list) unweaned alcoholism, substance abuse, non-compliance with usual follow-up visits)

secondary exclusion criteria:

- Evidence of collateral ventilation measured by the Chartis system

Primary outcomes:
measure: Pneumothorax rate
timeFrame: 45 day
Secondary outcomes:
measure: Forced expiratory volume in one second (FEV1) measurement
timeFrame: 0 Day, 45 Day, 6 month and 12 month
measure: Force Vital Expiratory (FVE) measurement
timeFrame: 0 Day, 45 Day, 6 month and 12 month
measure: Functional Residual Capacity (FRC) measurement
timeFrame: 0 Day, 45 Day, 6 month and 12 month
measure: Inspiratory Capacity (IC) measurement
timeFrame: 0 Day, 45 Day, 6 month and 12 month
measure: Residual Volume (RV) measurement
timeFrame: 0 Day, 45 Day, 6 month and 12 month
measure: Residual Volume (RV) / Total Lung Capacity (TLC) ratio
timeFrame: 0 Day, 45 Day, 6 month and 12 month
measure: Exercise tolerance
timeFrame: 0 Day, 45 Day, 6 month and 12 month
measure: Quality of life questionnaire
timeFrame: 0 Day, 45 Day, 6 month and 12 month
measure: Quality of life questionnaire
timeFrame: 0 Day, 45 Day, 6 month and 12 month
measure: Quality of life questionnaire
timeFrame: 0 Day, 45 Day, 6 month and 12 month
measure: lobe volume reduction
timeFrame: 45 Day
measure: Respiratory events
timeFrame: 12 month
measure: Events related to the valves
timeFrame: 12 month
measure: Revision bronchoscopies
timeFrame: 12 month
measure: Death
timeFrame: 12 month
measure: responder's rate
timeFrame: 12 month
measure: Incremental Cost-Utility Ratio (ICUR)
timeFrame: 12 month
Other outcomes:
Locations:
city: Bordeaux
country: France
facility: CHU de Bordeaux
city: Brest
country: France
facility: CHU de Brest
city: Dijon
country: France
facility: CHU de Dijon
city: Grenoble
country: France
facility: chu de Grenoble
city: Lille
country: France
facility: CHU de Lille
city: Limoges
country: France
facility: CHU de Limoges
city: Marseille
country: France
facility: APHM
city: Marseille
country: France
facility: Hopital Saint Joseph
city: Nice
country: France
facility: CHU de Nice
city: Paris
country: France
facility: APHP
city: Paris
country: France
facility: APHP
city: Rouen
country: France
facility: CHU de Rouen
city: Strasbourg
country: France
facility: chu de Strasbourg
city: Suresnes
country: France
facility: Hopital Foch
city: Toulouse
country: France
facility: chu de Toulouse
Study officials:
References: