Clinical trial NCT02047773: Bacterial Load Guided Therapy for Severe Bronchiectasis Exacerbations
Official title: Bacterial Load Guided Therapy for Severe Exacerbations of Bronchiectasis Requiring IntraVenous Antibiotic Therapy- BLT Br IV Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Bronchiectasis
Keywords: bronchiectasis
intravenous antibiotics
duration of antibiotic course
side effects
bacterial load
Lead sponsor: University of Edinburgh
Sponsor class: OTHER
Collaborators: name: NHS Lothian
First posted: 2014-01-28
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: From the British Thoracic Guidelines1 and a PUBMED search there are no randomised controlled trials exploring optimum antibiotic duration for chest infections. The standard course of intravenous antibiotics for exacerbations of bronchiectasis is 14 days. This is a preliminary open labelled study to assess whether it is feasible to stop treatment earlier (day 8 or day 11) if the bacterial load is low or absent at days 7 or day 10 (it takes 24 hours for the results to be processed). All patients will therefore have a minimum of 7 days intravenous antibiotics. The intravenous antibiotic chosen is routinely used for exacerbations in bronchiectasis.

Our hypothesis is that patients could have personalised treatment and be able to stop antibiotics when the sputum bacterial load is low (\<10\^6 colony forming units/ml (cfu/ml)).

Detailed description: We will investigate 90 patients with bronchiectasis who are developing an exacerbation as defined by the British Thoracic Society guidelines requiring intravenous antibiotics.

After being consented, patients will be randomly allocated to one of two arms (computer generated). 45 patients will have length of treatment guided by the bacterial load and 45 patients will have 14 days IV Meropenem.

Next they will all attend for their baseline visit. Here, they will be asked to provide a 24 hour sputum collected the day prior to the visit, a spontaneous sample collected within 4 hours from rising (sample used for sputum colour and microbiological analysis), undergo spirometry testing, incremental shuttle walk test, blood sampling (for inflammatory markers Erythrocyte Sedimentation Rate, C Reactive Protein, Full Blood Count, procalcitonin), fill out a leicester cough questionnaire to assess their cough (LCQ) and a health related quality of life questionnaire (St George's respiratory questionnaire, SGRQ).

All patients will be started on intravenous meropenem 2g, tds (assuming no previous documented resistant microbiology results or allergies).

They will all return on day 7 for a check on their clinical progress. At this time they will again provide a 24hour sputum, spontaneous sputum sample and blood samples as documented above. Arm one (intervention arm) will have their antibiotics stopped on day 8 if the bacterial load is less than 10\^6cfu/ml. Arm two will continue intravenous meropenem regardless of bacterial count.

All patients will return again on day 10, they will again provide a 24hour sputum, spontaneous sputum sample and blood samples as documented above. Arm one (intervention arm) will have their antibiotics stopped on day 11 if the bacterial load is less than 10\^6cfu/ml. Arm two will continue intravenous meropenem regardless of bacterial count.

All patients will return on day 14. All above assessments as on baseline will be repeated except the LCQ and SGRQ. All antibiotics for all patients will stop after 14 days of treatment.

All patients will return on day 21 where all the above assessments will be repeated. The LCQ and SGRQ will be completed on day 21. The date of and time to next exacerbation will be recorded at the next routine outpatient appointment.

Eligibility criteria: Inclusion Criteria:

* Patients aged 18 and above
* An established primary diagnosis of non cystic fibrosis bronchiectasis
* Patients need to meet the criteria for needing intravenous antibiotic therapy.
* Only the first exacerbation per patient will be used.

Exclusion Criteria:

* Patients with organisms resistant in vitro to Meropenem (this is known from previous sputum microbiology but is rare in our cohort);
* Current smokers or ex-smokers of less than 1 year;
* Cystic fibrosis;
* Active allergic bronchopulmonary aspergillosis;
* Active tuberculosis;
* Poorly controlled asthma necessitating long term oral corticosteroids;
* Pregnancy or breast feeding;
* Active malignancy;
* Severe chronic obstructive pulmonary disease (COPD) on long term oxygen therapy;
* Patients requiring non invasive or invasive ventilation;
* Known allergy to Meropenem which is very rare in our cohort.

Primary outcomes:
measure: Time to next exacerbation
timeFrame: up to 1 year following IV antibiotics
measure: Proportion of patients that stopped antibiotics early
timeFrame: 14 days
Secondary outcomes:
measure: Clinical recovery at days 14 and 21
timeFrame: 21 days
measure: Correlation of bacterial load with clinical response
timeFrame: 21 days
measure: Antibiotic side effects
timeFrame: 14 days
Other outcomes:
Locations:
city: Edinburgh
country: United Kingdom
facility: Royal Infirmary of Edinburgh
Study officials:
affiliation: NHS Lothian
name: Adam T Hill, MBCHB, MRCP, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bedi P, Cartlidge MK, Zhang Y, Turnbull K, Donaldson S, Clarke A, Crowe J, Campbell K, Graham C, Franguylan R, Rossi AG, Hill AT. Feasibility of shortening intravenous antibiotic therapy for bronchiectasis based on bacterial load: a proof-of-concept randomised controlled trial. Eur Respir J. 2021 Dec 16;58(6):2004388. doi: 10.1183/13993003.04388-2020. Print 2021 Dec.