Bacterial Load Guided Therapy for Severe Bronchiectasis Exacerbations

NCT02047773 | Completed Phase 4

• 1 other identifier: BLTBrIVStudy
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

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)).

Conditions

Bronchiectasis

Keywords

bronchiectasis; intravenous antibiotics; duration of antibiotic course; side effects; bacterial load

Outcome Measures

Primary Outcomes (2)

• Time to next exacerbation

  The time to next exacerbation (all the patients are followed up in the bronchiectasis clinic and record the date of their exacerbations where they receive antibiotic therapy).

  up to 1 year following IV antibiotics

• Proportion of patients that stopped antibiotics early

  The proportion of patients where we can stop antibiotic treatment early guided by bacterial load either on day 8 or day 11 instead of usual day 14 course. All patients will have a minimum of 7 days of intravenous antibiotics.

  14 days

Secondary Outcomes (3)

• Clinical recovery at days 14 and 21

  21 days

• Correlation of bacterial load with clinical response

  21 days

• Antibiotic side effects

  14 days

Study Arms (2)

14 days Duration

PLACEBO COMPARATOR

14 days of antibiotics regardless of bacterial load.

Drug: Colomycin

Bacterial load guided duration

ACTIVE COMPARATOR

Antibiotics stopped early on day 8 or day 11 if the bacterial load when checked on day 7 and day 10 is less than 10\^6cfu/ml.

Other: Duration; Drug: Colomycin; Drug: Meropenem

Interventions

Duration OTHER

If bacterial load checked on day 7 is less than 10\^6 cfu/ml then antibiotics will be stopped on day 8 (results take 24hrs). If bacterial load remains higher than this then patients will continue on intravenous antibiotics. Bacterial load will be checked again on day 10. If bacterial load is less than 10\^6 cfu/ml then antibiotics will be stopped on day 11. If bacterial load remains higher than this then the patient will complete a 14day course of antibiotics. All patients will be seen and bacterial load assessed on day 1, day 7, day 10, day 14 and day 21.

Bacterial load guided duration

Colomycin DRUG

If there is a clinical deterioration a second antibiotic to augment treatment (Colomycin) will be added for both arms of the study.

14 days Duration; Bacterial load guided duration

Meropenem DRUG

Bacterial load guided duration

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Edinburgh: lead
• NHS Lothian: collaborator

Study Sites (1)

Royal Infirmary of Edinburgh

Edinburgh, EH16 4SA, United Kingdom

Location

Related Publications (2)

• Hill AR, Bedi P, Cartlidge MK, Turnbull K, Donaldson S, Clarke A, Crowe J, Campbell K, Franguylan R, Rossi AG, Hill AT. Early Exacerbation Relapse is Increased in Patients with Asthma and Bronchiectasis (a Post hoc Analysis). Lung. 2023 Feb;201(1):17-23. doi: 10.1007/s00408-023-00601-1. Epub 2023 Feb 6.

  PMID: 36746812 DERIVED

• 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.

  PMID: 34112732 DERIVED

MeSH Terms

Conditions

Bronchiectasis

Interventions

Time; Meropenem

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Physical Phenomena; Thienamycins; Carbapenems; beta-Lactams; Lactams; Amides; Organic Chemicals; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Adam T Hill, MBCHB, MRCP, MD

  NHS Lothian

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 22, 2014
• First Posted: January 28, 2014
• Study Start: January 1, 2014
• Primary Completion: February 1, 2020
• Study Completion: February 1, 2020
• Last Updated: May 4, 2020

Record last verified: 2020-05

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)