Microdosing of BAC ONE to the Distal Lung

University of Edinburgh

Status and phase

Completed

Early Phase 1

Conditions

Bacterial Respiratory Infections

Treatments

Other: BAC ONE administration

Study type

Interventional

Funder types

Other

Identifiers

NCT02558062

BAC ONE

Details and patient eligibility

About

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.

Full 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.

Enrollment

14 patients

Sex

All

Ages

16+ years old

Volunteers

No 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.
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