Exploratory Study of Intrapulmonary Microdosing of Gram-negative Optical Imaging Detection Probe

NCT02491164 | Completed Early Phase 1 DMC

• 1 other identifier: BAC TWO
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

Critically ill patients are often ventilated in dedicated critical care units to provide respiratory support. Despite best practice patients can often develop a condition called adult respiratory distress syndrome (ARDS), which is characterised by deterioration in their respiratory function, and changes on chest x-ray. The correct management for ARDS is identifying the underlying condition causing the deterioration and identifying appropriate targeted therapy. One such cause is pneumonia, caused by a bacterial infection in the lungs of a ventilated patient. The patients may have been ventilated due to pneumonia but they may also develop pneumonia whilst ventilated. Ventilator associated pneumonia (VAP) has significant mortality. Despite all the clinical and laboratory data at the investigators' disposal there remains great difficulty in the accurate diagnosis of pneumonia and therefore treatment is often given empirically. Therefore, there is an urgent clinical need for accurate methods to diagnose the presence of bacteria deep in the lung in ventilated critically ill patients. As such, the investigating team have developed and synthesised an imaging agent called BAC TWO. BAC TWO will be instilled directly into the lungs of 12 patients to assess whether it can label gram-negative bacteria in the human lung.

Conditions

Respiratory Infections

Outcome Measures

Primary Outcomes (1)

• Imaging parameters of BAC TWO in the distal lung

  The main primary outcome measure is to visualise the delivery of BAC TWO in the distal lung of both ventilated controls and patients with gram-negative bronchiectasis, gram-positive bronchiectasis and pulmonary infiltrates through the measurement of fluorescence using FE and Cellvizio viewer software.

  up to 1 week post dose

Study Arms (1)

BAC TWO administration

EXPERIMENTAL

All participants in this clinical study will be dosed on one occasion with BAC TWO. The final dosage will be 80 µg (± 25%).

Other: BAC TWO; Device: FE and Cellvizio viewer software

Interventions

BAC TWO OTHER

BAC TWO administration

BAC TWO administration

FE and Cellvizio viewer software DEVICE

Fibre based endomicroscopy to visualise fluorescent signal emitted by optical agents.

BAC TWO administration

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• All cohorts
• ≥ 16 years
• Attending consultant permission for bronchoscopy
• Cohort 1
• Patients scheduled to undergo surgery under general anaesthesia
• Absence of acute or significant chronic lung disease as determined by the clinical suspicion of the attending medical team or of a medically qualified member of the study investigation team.
• Presence or scheduled presence of endo-tracheal tube.
• Capacity to provide informed consent
• Cohort 2 and 3
• Patients with bronchiectasis with known microbiological predominance of gram-negative or gram-positive bacteria.
• Capacity to provide informed consent
• Cohort 4
• Patients in the ICU with pulmonary infiltrates on radiological assessment
• Presence of invasive tracheal ventilation tube
• Provision of informed consent from the patient or their personal legal representative prior to any study related procedures.

You may not qualify if:

• All cohorts
• Refusal for participation by attending consultant
• Any history of anaphylaxis or allergy to polymyxin-based antibiotics e.g. colomycin
• Significant coagulopathy, which causes bronchoscopy to be unsuitable, as determined by clinical co-investigator or the participant's attending consultant, using information which is routinely available
• Myocardial infarction in the preceding four weeks
• Women who are pregnant or are breastfeeding
• Receiving drugs that cause increased autofluorescence in the lung, specifically amiodorane and methotrexate
• Cohort 4 only
• Inspired Oxygen Concentration (FiO2) \>70%
• Positive End Expiratory Pressure (PEEP) \>10cm
• Endotracheal tube (ETT) or tracheostomy internal diameter \< 7mm
• Presence of pneumothorax
• Active bronchospasm
• Mean arterial pressure \<65mmHg (millimeter of mercury) AND on vasopressor
• Platelet count \< 50 x 109/L

Sponsors & Collaborators

• University of Edinburgh: lead
• NHS Lothian: collaborator

Study Sites (1)

Royal Infirmary Edinburgh

Edinburgh, EH16 4TJ, United Kingdom

Location

MeSH Terms

Conditions

Respiratory Tract Infections

Condition Hierarchy (Ancestors)

Infections; Respiratory Tract Diseases

Study Officials

• Kev Dhaliwal, MBChB

  University of Edinburgh

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 1, 2015
• First Posted: July 7, 2015
• Study Start: April 1, 2016
• Primary Completion: June 1, 2018
• Study Completion: June 1, 2018
• Last Updated: March 26, 2020

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)