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Exploratory Study of Intrapulmonary Microdosing of Gram-negative Optical Imaging Detection Probe (BAC TWO)

Primary Purpose

Respiratory Infections

Status

Completed

Phase

Early Phase 1

Locations

United Kingdom

Study Type

Interventional

Intervention

BAC TWO

FE and Cellvizio viewer software

About this trial

This is an interventional other trial for Respiratory Infections

Eligibility Criteria

16 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Royal Infirmary Edinburgh

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

BAC TWO administration

Arm Description

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Full Information

NCT ID

NCT02491164

First Posted

July 1, 2015

Last Updated

March 24, 2020

Sponsor

University of Edinburgh

Collaborators

NHS Lothian

1. Study Identification

Unique Protocol Identification Number

NCT02491164

Brief Title

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

Acronym

BAC TWO

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

March 2020

Overall Recruitment Status

Completed

Study Start Date

April 2016 (Actual)

Primary Completion Date

June 2018 (Actual)

Study Completion Date

June 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of Edinburgh

Collaborators

NHS Lothian

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Respiratory Infections

7. Study Design

Primary Purpose

Other

Study Phase

Early Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

18 (Actual)

8. Arms, Groups, and Interventions

Arm Title

BAC TWO administration

Arm Type

Experimental

Arm Description

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

Intervention Type

Other

Intervention Name(s)

BAC TWO

Intervention Description

BAC TWO administration

Intervention Type

Device

Intervention Name(s)

FE and Cellvizio viewer software

Intervention Description

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

Primary Outcome Measure Information:

Title

Imaging parameters of BAC TWO in the distal lung

Description

Time Frame

up to 1 week post dose

10. Eligibility

Sex

All

Minimum Age & Unit of Time

16 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Kev Dhaliwal, MBChB

Organizational Affiliation

University of Edinburgh

Official's Role

Principal Investigator

Facility Information:

Facility Name

Royal Infirmary Edinburgh

City

Edinburgh

ZIP/Postal Code

EH16 4TJ

Country

United Kingdom

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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