Evaluating the Safety and Efficacy of dNerva Lung Denervation System in Patients With COPD

Официальное название

A Multicenter, Randomized, Study to Evaluate Safety and Efficacy After Treatment With the dNerva Lung Denervation System in Subjects With Chronic Obstructive Pulmonary Disease (COPD) (AIRFLOW-4)

Обзор

The dNerva Lung Denervation System is one-time treatment intended to improve breathing in Chronic Obstructive Pulmonary Disease (COPD) patients on standard medical care. The purpose of this study is to confirm the safety and efficacy of the Nuvaira Lung Denervation System in the treatment of COPD.

Подробное описание

The primary objective of this study is to demonstrate the superiority of treatment with the dNerva Lung Denervation System on top of standard medical care (Treatment arm) compared to standard medical care alone (Control arm) to improve lung function in COPD participants with high RV and low emphysema.

The secondary objective is to compare other efficacy assessments between the Treatment arm and the Control arm, and to confirm the safety profile of lung denervation.

Вмешательства

• Устройство Targeted Lung Denervation (TLD)
  Targeted Lung Denervation (TLD)Therapy is a bronchoscopically guided minimally invasive one-time treatment using the dNerva Lung Denervation System.

Первичные конечные точки

• The primary endpoint is improvement in FEV1 at 6 months. [Срок оценки: 6 months]

Вторичные конечные точки (5)

• Change in Post-BD FEV1 [Срок оценки: 12 months]
• Change in Post-BD RV [Срок оценки: 12 months]
• Transition Dyspnea Index (TDI) [Срок оценки: 12 months]
• Change in SGRQ-C [Срок оценки: 12 months]
• Annualized rate of Moderate and Severe COPD Exacerbations [Срок оценки: 91 days to 12 months.]

Критерии участия

Критерии включения

• ≥ 40 and ≤ 80 years of age at the time of consent.
• Women of childbearing potential must not be pregnant, evidenced by a negative pregnancy test (blood or urine) pre-treatment, or lactating and agree not to become pregnant for the duration of the study.
• Smoking history of at least 10 pack years.
• Not smoking or using any other inhaled substance (e.g. cigarettes, vaping, cannabis, pipes) for a minimum of 2 months prior to consent and agrees to not start for the duration of the study.
• Resting SpO2 ≥ 89% on room air.
• MMRC ≥ 2; CAT score ≥ 10.
• Diagnosis of moderate to severe COPD as defined by FEV1/FVC < 70% (post-bronchodilator), 25% ≤ FEV1 ≤ 70% predicted, and PaCO2 < 50 (if FEV1 < 30%).
• RV ≥ 175% of predicted and RV/TLC > 55% (post-bronchodilator).
• Participant is on standard medical care, defined as a minimum of therapy with LABA/ICS, LAMA/LABA, or LAMA/LABA/ICS for at least 2 months prior to consent.
• If subject has participated in a formal pulmonary rehabilitation program recently, program completion must have occurred ≥3 months prior to consent; if in a maintenance program, subject agrees to continue their current program through their 12-month follow-up visit; NOTE: Prior participation in a pulmonary rehabilitation program is not required for inclusion in the study.
• Participant is a candidate for bronchoscopy in the opinion of the investigator or per hospital guidelines and is able to discontinue blood thinning medication peri-procedurally.
• Participant is able and agrees to complete all protocol required baseline and follow up tests and assessments including taking certain medications (e.g., azithromycin, prednisolone/prednisone).

Критерии исключения

• Body Mass Index (BMI) <18 or >32.
• Participant has an implantable electronic device and has not received appropriate medical clearance.
• Uncontrolled diabetes in the opinion of the investigator.
• 4 or more respiratory related hospitalizations within 1 year of consent.
• Malignancy treated with radiation or chemotherapy within 1 year of consent.
• Participant diagnosed with a dominant non-COPD lung disease, or condition affecting the lungs, which is the main driver of the participant's clinical symptoms (e.g., cystic fibrosis, paradoxical vocal cord motion, eosinophilic granulomatosis with polyangiitis (EGPA), allergic bronchopulmonary aspergillosis, interstitial lung disease or active tuberculosis or Asthma) or has a documented medical history of pneumothorax within 1 year of consent.
• Clinically relevant bronchiectasis, defined as > 1/3 cup mucous expectoration daily.
• Pre-existing diagnosis of pulmonary hypertension, clinical evidence of pulmonary hypertension (e.g., cardiovascular function impairment including peripheral edema) and mPAP ≥25 mmHg at rest by right heart catheterization (or estimated right ventricular systolic pressure >50 mmHg by echocardiogram if no previous right heart catheterization).
• Myocardial infarction within last 6 months, evidence of life-threatening arrhythmias or acute ischemia, pre-existing documented evidence of a LVEF < 40%, stage C or D (ACC/AHA) or Class III or IV (NYHA) congestive heart failure.
• Surgical procedure(s) on the stomach, esophagus or pancreas performed ≤2 years of consent, or ongoing related symptoms within the past year.
• Symptomatic gastric motility disorder(s) (e.g., gastroparesis) as evidenced by GCSI score ≥18.0, severe uncontrolled GERD (e.g., refractory heartburn, endoscopic esophagitis) or severe dysphagia (e.g., esophageal stricture, achalasia, esophageal spasm). NOTE: Participants with a hiatal hernia are allowed if Participant meets all other enrollment criteria.
• Any disease or condition that might interfere with completion of a procedure or this study (e.g., structural esophageal disorder, life expectancy <3 years).
• Prior lung or chest procedure (e.g., BLVR explant procedure, median sternotomy, bullectomy, lobectomy, segmentectomy or other interventional lung or chest procedure) performed ≤1 year of consent? Participants with lung transplant, BLVR valves, LVRS, metal stents within 5cm of the anticipated treatment location; presence of lung volume reduction valves, coils or other lung implants.
• Daily use of >20 mg of prednisone or its equivalent at the time of consent.
• Known contraindication or allergy to medications required for bronchoscopy or general anesthesia (e.g., lidocaine, atropine, propofol, sevoflurane) that cannot be medically controlled.
• Baseline chest CT scan reveals bronchial anatomy cannot be treated with available catheter sizes; presence of whole lung emphysema >20% (-950 HU), single lung emphysema >26% (-950 HU), severe bullous disease (>1/3 hemithorax) or discovery of a mass that requires treatment.
• Participant is currently enrolled in another drug or interventional clinical trial that has not completed follow-up.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 10 центров

• University of Alabama-Birmingham Hospital - UAB Lung Health Center — Birmingham
• Mayo Clinic Jacksonville — Jacksonville
• Henry Ford Hospital - Lung and Pulmonary Care — Detroit
• Wake Forest School of Medicine — Salem
• Ohio State University Medical Center - Ohio State Lung Center — Columbus
• Penn Highlands - Lung Innovations/Clinical Research Associates — DuBois
• Temple University - Temple Lung Center — Philadelphia
• University of Pittsburgh Medical Center - UMPC Comprehensive Lung Center — Pittsburgh
• … и ещё 2 центра

Идентификаторы

NCT: NCT07051707 · D0836

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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