Endobronchial Valve in Tubercular and NTM Pulmonary Cavities.

N/ANot Yet RecruitingNCT07296055

Azienda Ospedaliero-Universitaria Careggi30 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Interventions

Endobronchial valvesDEVICE

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.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 80 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Age between 18 and 80 years AND 2. 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 3. To have signed the informed consent AND one of the following conditions: 4. 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. 5. 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. 6. Recurrent haemoptysis attributable to TB or NTM Exclusion Criteria: 1. Contraindication to performance of bronchoscopy 2. Severe cardiac comorbidities 3. Severe psychiatric disorders 4. Functional or anatomical pneumonectomy 5. Asthma 6. Pregnancy 7. Patients for whom bronchoscopic procedures are contraindicated 8. Patients with known allergies to Nitinol (nickel-titanium) or its constituent metals (nickel or titanium) 9. Patients with known allergies to silicone 10. Patients who have not quit smoking 11. Patients with large bullae encompassing greater than 30% of either lung 12. Patients with active pulmonary infection

Outcomes

Primary Outcomes

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.

Time frame: 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.

Time frame: 9 months after the randomization

Secondary Outcomes

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

The difference of cavity assial diameter, expressed in mm, between each timepoints and baseline. Differences will be expressed in median and in interquartile range in each arm.

Time frame: 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

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

Time frame: 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 each timepoints sputum will be collected and cultered. The culture will be observed through optical microscopy for 8 weeks. If after 8 weeks no microbacterial growth will be observed, the negativity will be diagnosed for that sample. The results wil be expressed in CFU.

Time frame: 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.

In the experimental arm Zephyr the complications that arise within 48 hours are defined early, events after 48 hours, will be defined late complications. The severity of the complication will be assessed by CTCAE v4.0.

Time frame: 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 intervention, the correct valve position will be confirmed through CT scan. The results will be expressed as the proportion between patients that undergone for the valve reposition and total patients evaluated at 3 months.

Time frame: At 3 months after the intervention.