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Microdosing of BAC ONE to the Distal Lung (BAC ONE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02558062
Recruitment Status : Completed
First Posted : September 23, 2015
Last Update Posted : March 26, 2020
NHS Lothian
Information provided by (Responsible Party):
University of Edinburgh

Tracking Information
First Submitted Date  ICMJE September 17, 2015
First Posted Date  ICMJE September 23, 2015
Last Update Posted Date March 26, 2020
Actual Study Start Date  ICMJE May 2016
Actual Primary Completion Date December 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 22, 2015)
The measurement of BAC ONE fluorescence intensity in the distal lung [ Time Frame: Fluorescence signal can be detected within a couple of minutes following BAC ONE administration. On average, signal analysis will be completed within one week of the procedure. ]
The main primary outcome measure is to visualise the delivery of BAC ONE in the distal lung of both ventilated controls and patients with acute or chronic bacterial lung infection through the measurement of fluorescence using FE and Cellvizio viewer software.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Microdosing of BAC ONE to the Distal Lung
Official Title  ICMJE Exploratory Clinical Study of Intrapulmonary Microdosing of the BACterial Detection Probe (BAC ONE) in Ventilator Associated Pneumonia
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 ONE. BAC ONE will be instilled directly into the lungs of 12 patients (with and without lung infection) to assess whether it can label bacteria in the human lung.

Detailed Description

The primary objective of this study is to deliver a BAC ONE microdose to ventilated controls and patients with lung infection to assess the imaging parameters of BAC ONE over human autofluorescence and to assess if bacteria can be detected in vivo in situ within the distal lung.

The primary endpoint is to visualise the delivery of a microdose of BAC ONE and assess imaging parameters in:

  • 3 mechanically ventilated patients to provide a control population (cohort 1)
  • 6 bronchiectasis patients with predominant colonisation with gram-negative bacteria (cohort 2)
  • 6 bronchiectasis patients with predominant colonisation with gram-positive bacteria (cohort 3)
  • 3 patients with suspected pneumonia and pulmonary infiltrates in ICU (cohort 4)

For all cohorts, eligibility will be verified by a clinical trial physician after written informed consent has been obtained. For all cohorts, a bronchoscopy with lavage will be performed to harvest broncho-alveolar lavage fluid (BALF). Fibre-based endomicroscopy (FE) will be performed on up to three areas and up to 80μg (± 25%) in total of BAC ONE will be instilled in up to 3 sites.

Participants will be asked to provide additional blood and urine samples with the intention of examining for systemic uptake of the BAC ONE probe. Routine blood investigations will be performed 4-6 hours following the administration of BAC ONE. All participants will either be contacted by a member of the research team via telephone or ward visit 24 hours (± 4 hours) after BAC ONE dosing to ensure no AEs/SAEs were experienced. The participant's involvement in the study is concluded when the 24 hour assessment has been successfully completed and all AEs/SAEs have been resolved.

Study Type  ICMJE Interventional
Study Phase  ICMJE Early Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
Condition  ICMJE Bacterial Respiratory Infections
Intervention  ICMJE Other: BAC ONE administration
BAC ONE will be administered to each patient during a bronchoscopy procedure. Fibre-based endomicroscopy and Cellvizio viewer software will be used to detect BAC ONE signal in the distal lung.
Other Name: BAC ONE
Study Arms  ICMJE Experimental: BAC ONE administration
All participants in this clinical study will be dosed on one occasion with BAC ONE. The final dosage will be 80 µg (± 25%).
Intervention: Other: BAC ONE administration
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 24, 2020)
Original Estimated Enrollment  ICMJE
 (submitted: September 22, 2015)
Actual Study Completion Date  ICMJE December 2018
Actual Primary Completion Date December 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

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.
  • Scheduled presence of an endo-tracheal tube (ETT).
  • 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 suspected VAP and 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.

Exclusion Criteria:

All cohorts

  • Refusal for participation by attending consultant
  • Any history of anaphylaxis
  • 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

Participants in cohort 4 only

  • Inspired Oxygen Concentration (FiO2) >70%
  • Positive End Expiratory Pressure (PEEP) >10cm
  • ETT or tracheostomy internal diameter < 7mm
  • Presence of pneumothorax
  • Active bronchospasm
  • Mean arterial pressure <65mmHg AND on vasopressor
  • Platelet count < 50 x 109/L
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 16 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United Kingdom
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT02558062
Other Study ID Numbers  ICMJE BAC ONE
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party University of Edinburgh
Study Sponsor  ICMJE University of Edinburgh
Collaborators  ICMJE NHS Lothian
Investigators  ICMJE
Study Director: Kev Dhaliwal, MBChB University of Edinburgh
PRS Account University of Edinburgh
Verification Date March 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP