Endobronchial Valve in Tubercular and NTM Pulmonary Cavities.

NCT07296055 | Not Yet Recruiting DMC FDA Device

• 2 other identifiers: 26268_spe25-01-050896
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Tuberculosis (TB) is a complex disease in which the lungs are the primary site of infection. Infection is acquired through inhalation of droplet nuclei laden with Mycobacterium bacilli (M. tuberculosis) that settle in the alveoli as the primary focus. TB is characterized by a gradual expansion of infection and cavitation that causes progressive tissue destruction. Furthermore, the increase in drug-resistant forms of TB, including multidrug resistance (MDR) and pre-extensively drug-resistant TB (XDR), is becoming increasingly concerning. Treatment of pharmacosensitive diseases involves a duration of no less than 6 months, while that of MDR-TB and XDR-TB are even longer; generally well above 24 months. Nontuberculous mycobacteria (NTMs), or atypical mycobacteria, are organisms that cause various diseases such as skin and soft tissue infections, lymphadenitis, lung infections, disseminated infections, and a wide range of more rarely encountered infections that do not differ from tuberculosis in anatomy and radiologically even though they usually do not develop the primary complex. Given that the treatment success rate is unsatisfactory, there is an urgent need for new drugs and additional interventions to improve outcomes, both in patients with MDR/XDR-TB and in patients with difficult-to-treat NTM. One-way endobronchial valves (EBVs) have been used as an effective lung volume reduction strategy in emphysema without significant adverse events. The mechanism consists in inducing atelectasis, that is, creating a poorly ventilated environment with reduced oxygen tension. This reduced oxygen tension is unfavorable for the survival and proliferation of mycobacteria. Therefore, using these devices to treat cavities caused by multidrug-resistant mycobacteria or in patients not eligible for surgical therapy should reduce or completely heal the cavity, creating an inhospitable environment for the bacteria, slowing or eliminating their growth. Condition/disease: Pulmonary MDR/XDR-TB or NTM (difficult to treat or resistant to treatment) Number of patients to be enrolled: 30 It is a single-center, randomized, controlled, open-label, two-arm study.

Conditions

Multidrug Resistance Tubercolosis; Non Tubercolar Micobacteriosis

Keywords

Endobronchial valves; Non Tubercolar Micobacteriosis; Multidrug Resistance Tubercolosis

Outcome Measures

Primary Outcomes (2)

• Percentage of patients with cavities reduction equal or above 50% in the two arms

  Percentage of patients with cavity dimension, at 9 months of treatment, \< or = to 50% of cavity dimension at baseline. The results will be expressed in mm, through the maximum axial diameter. Higher percentage in the experimetal arm Zephyr suggests the efficacy of the treatment.

  At 9 months after the randomization

• Percentage of patients with sputum smear negative for microbiological agents in the two arms at 9 months of treatment

  The sputum smear for microbiological agents will be collected on a slide and then observed through optical microscopy. The results will be expressed in dichotomous scale. Higher percentage of negative results in the experimental arm Zephyr suggests the efficacy of the treatment.

  9 months after the randomization

Secondary Outcomes (5)

• Median of cavity dimension differences at each timepoints in comparison with baseline in both arms.

  At 3 months and 9 months after the randomization

• Percentage of patients with sputum smear negative for microbiological agents in the two arms, at each timepoints

  At 1, 3, 9 months after randomization and at 12, 14 months at the follow up

• Percentage of culture negative for microbiological agents at each timepoint among the two arms.

  At 1, 3, 9 months after the randomization and 12, 14 months at the follow up

• Percentage of patients with early (within 48 hours) and late complications in the experimental arm Zephyr.

  At T0 (intervention)+48 hours, 3 and 9 months after intervention.

• Percentage of patients who have undergone valve reposition in experimental arm Zephyr.

  At 3 months after the intervention.

Study Arms (2)

Zephyr ®

EXPERIMENTAL

Patients will be randomized in the two arms. All patients will continue antibiotic therapy as per clinical practice. Within 30 days the patients allocated to the experimental arm will be contacted to schedule bronchoscopy for valve placement. The treatment will be performed on a day hospital basis, patients will undergo Chest X-rays before discharge in order to confirm correct valve placement. After 9 month the experimental arm will undergone a procedure in order to remove valves.

Device: Endobronchial valves

Control

NO INTERVENTION

Patients randomized in control arm will continue antibiotic therapy as per clinical practice.

Interventions

Endobronchial valves DEVICE

Patients shall undergo a bronchoscopy in sedation using midazolam and/or fentanyl or general anaesthesia with propofol in some cases. For MDR - TB patients the procedure will be done in an isolation room with negative pressure. Rigid bronchoscopy, facial or laryngeal mask airway shall be employed to introduce the fiberoptic bronchoscope, an instrument equipped with an operating channel of variable diameter between 2.8 and 3.2 mm that allows insertion of the valve. The Zephyr ® EBV is a self-expandable system which is actuated to contact with the bronchial wall, facilitating adhesion to the bronchial wall and moulding in conformity with the bronchial anatomy. Being one-way valves, that prevent the ingress of the air to the segment or lobe under consideration, while allowing, egress of the same during exhalation.

Also known as: no interventions

Zephyr ®

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age between 18 and 80 years AND
• Patient with cavities deemed unsuitable for surgery (when an extensive pulmonary parenchymal damage due to TB, is present, making patients inappropriate for open thoracic surgery) AND
• To have signed the informed consent
• AND one of the following conditions:
• Pulmonary MDR/XDR -TB or NTM (difficult to treat or resistant to treatment) confirmed by smear samples and antibiogram or with persistence of positivity for Mycobacterium of the smear after standard pharmacotherapy and severe destruction of the lungs with 1 or more persistent cavities.
• Pulmonary TB or NTM with cavities and associated systemic diseases such as pancreatic diabetes, stomach and duodenum ulcer, liver and kidney diseases, HIV or another such disease that compromises pharmacological treatment.
• Recurrent haemoptysis attributable to TB or NTM

You may not qualify if:

• Contraindication to performance of bronchoscopy
• Severe cardiac comorbidities
• Severe psychiatric disorders
• Functional or anatomical pneumonectomy
• Asthma
• Pregnancy
• Patients for whom bronchoscopic procedures are contraindicated
• Patients with known allergies to Nitinol (nickel-titanium) or its constituent metals (nickel or titanium)
• Patients with known allergies to silicone
• Patients who have not quit smoking
• Patients with large bullae encompassing greater than 30% of either lung
• Patients with active pulmonary infection

Sponsors & Collaborators

• Azienda Ospedaliero-Universitaria Careggi: lead

Study Sites (1)

Azienda Ospedaliera Universitaria Careggi

Florence, FI, 50134, Italy

Location

Central Study Contacts

Lorenzo Corbetta

CONTACT

+39 055 7947628; lorenzo.corbetta@unifi.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 3, 2025
• First Posted: December 22, 2025
• Study Start: January 12, 2026
• Primary Completion (Estimated): May 12, 2028
• Study Completion (Estimated): December 12, 2028
• Last Updated: December 22, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)