Endobronchial Valve in Tubercular and NTM Pulmonary Cavities.
Trial statusNot yet recruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18-80
SponsorAzienda Ospedaliero-Universitaria Careggi
About this trial
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 criteria
This trial does not accept healthy volunteersQualifiers
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
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.
Disqualifiers
Contraindication to performance of bronchoscopy
Severe cardiac comorbidities
Severe psychiatric disorders
Functional or anatomical pneumonectomy
Trial design
Design model
Parallel
Treatments tested in this trial
Endobronchial valves
DevicePatients 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.
Treatment groups
30 Participants
are divided into 2 treatment groupsGroup A: Zephyr ®Experimental treatment 1 intervention
Group B: ControlNo intervention 0 interventions
Trial outcomes
Primary outcomes
1
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 randomization2
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 randomizationSecondary outcomes
1
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 randomization2
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 up3
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 up4
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.Sponsors and contacts
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Source ClinicalTrials.gov
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