Endobronchial Valve in Tubercular and NTM Pulmonary Cavities.

Condition(s) studied

Investigational drug(s) / intervention(s)

Endobronchial valves: 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.

Study 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.

Eligibility

Primary outcome measure(s)

• Percentage of patients with cavities reduction equal or above 50% in the two arms — At 9 months after the randomization
  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.
• Percentage of patients with sputum smear negative for microbiological agents in the two arms at 9 months of treatment — 9 months after the randomization
  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.

Trial sites (1)

More Azienda Ospedaliero-Universitaria Careggi trials in Italy