Bacterial Load Guided Therapy for Severe Bronchiectasis Exacerbations

NCT ID: NCT02047773

Last Updated: 2020-05-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 90 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-01-31
• Study Completion Date: 2020-02-01

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.

Conditions

Bronchiectasis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

14 days Duration

14 days of antibiotics regardless of bacterial load.

Group Type: PLACEBO_COMPARATOR

Colomycin

Intervention Type: DRUG

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

Bacterial load guided duration

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.

Group Type: ACTIVE_COMPARATOR

Duration

Intervention Type: 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.

Colomycin

Intervention Type: DRUG

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

Meropenem

Intervention Type: DRUG

Interventions

Duration

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.

Intervention Type: OTHER

Colomycin

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

Intervention Type: DRUG

Meropenem

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

NHS Lothian

OTHER_GOV

Sponsor Role: collaborator

University of Edinburgh

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Adam T Hill, MBCHB, MRCP, MD

Role: PRINCIPAL_INVESTIGATOR

NHS Lothian

Locations

Royal Infirmary of Edinburgh

Edinburgh, , United Kingdom

Countries

United Kingdom

References

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.

Reference Type: DERIVED

PMID: 36746812 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 34112732 (View on PubMed)

Other Identifiers

BLTBrIVStudy

Identifier Type: -

Identifier Source: org_study_id