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Trial record 1 of 1 for:    NCT02491164
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Exploratory Study of Intrapulmonary Microdosing of Gram-negative Optical Imaging Detection Probe (BAC TWO)

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ClinicalTrials.gov Identifier: NCT02491164
Recruitment Status : Completed
First Posted : July 7, 2015
Last Update Posted : March 26, 2020
NHS Lothian
Information provided by (Responsible Party):
University of Edinburgh

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.

Condition or disease Intervention/treatment Phase
Respiratory Infections Other: BAC TWO Device: FE and Cellvizio viewer software Early Phase 1

Detailed Description:

The primary objective of this study is to deliver a BAC TWO microdose to 3 ventilated controls and 9 patients to assess the imaging parameters of BAC TWO over human autofluorescence and to assess if gram-negative 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 TWO 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 TWO 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 TWO probe. Routine blood investigations will be performed 4-6 hours following the administration of BAC TWO. The completion of all assessments at 4-6 hours post dose marks the end of the participant's participation in this study unless there are ongoing adverse events requiring resolution. The primary aim will be measured during bronchoscopy and all routine investigations will have been completed 6 hours post dose.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 18 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: Exploratory Clinical Study of Intrapulmonary Microdosing of Gram-negative Optical Molecular Imaging BACterial Detection Probe
Actual Study Start Date : April 2016
Actual Primary Completion Date : June 2018
Actual Study Completion Date : June 2018

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: BAC TWO administration
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
BAC TWO administration

Device: FE and Cellvizio viewer software
Fibre based endomicroscopy to visualise fluorescent signal emitted by optical agents.

Primary Outcome Measures :
  1. Imaging parameters of BAC TWO in the distal lung [ Time Frame: up to 1 week post dose ]
    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.

Information from the National Library of Medicine

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Ages Eligible for Study:   16 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.
  • 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.

Exclusion Criteria:

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02491164

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United Kingdom
Royal Infirmary Edinburgh
Edinburgh, United Kingdom, EH16 4TJ
Sponsors and Collaborators
University of Edinburgh
NHS Lothian
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Principal Investigator: Kev Dhaliwal, MBChB University of Edinburgh
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Responsible Party: University of Edinburgh
ClinicalTrials.gov Identifier: NCT02491164    
Other Study ID Numbers: BAC TWO
First Posted: July 7, 2015    Key Record Dates
Last Update Posted: March 26, 2020
Last Verified: March 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Additional relevant MeSH terms:
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Respiratory Tract Infections
Respiratory Tract Diseases