BronchiectasisPhase 4BLTBrIVNCT02047773
Bacterial Load Guided Therapy for Severe Bronchiectasis Exacerbations
A Phase 4 study testing Duration, Colomycin and Meropenem in people with Bronchiectasis, run by University of Edinburgh at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Bronchiectasis
- What is being tested?
- Duration, Colomycin and Meropenem
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 90 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Jan 2014to 1 Feb 2020
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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;
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Bacterial Load Guided Therapy for Severe Exacerbations of Bronchiectasis Requiring IntraVenous Antibiotic Therapy- BLT Br IV Study
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)).
Read the 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
- Being tested
- Duration, Colomycin, Meropenem
- Keywords
- bronchiectasis, intravenous antibiotics, duration of antibiotic course, side effects, bacterial load
- Medical subject headings
- Bronchiectasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DurationOther
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.
ColomycinDrug
If there is a clinical deterioration a second antibiotic to augment treatment (Colomycin) will be added for both arms of the study.
MeropenemDrug
| Study group | Role | What they receive |
|---|---|---|
| 14 days Duration | Placebo comparator | 14 days of antibiotics regardless of bacterial load. Receives: 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. Receives: Other: Duration; Drug: Colomycin; Drug: Meropenem |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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.
Measured: 14 days
Secondary outcomes (3)
Clinical recovery at days 14 and 21
Clinical recovery defined in this study is based on our clinical experience and our study evaluating useful endpoints in monitoring exacerbations.
Clinical recovery is defined as: patients feeling better (quantitatively assessed using a 4 point or more improvement in St George's Respiratory Questionnaire or a 1.3 unit improvement or more in the Leicester Cough Questionnaire) and either a reduction in sputum purulence (purulent to mucopurulent, mucoid or no sputum; or mucopurulent to mucoid or no sputum) or a 50% reduction or more in 24 hour sputum volume. The reason for the two options here is that in clinical practice, some patients sputum purulence does not change but have a significant reduction in sputum volume.
Measured: 21 days
Correlation of bacterial load with clinical response
The correlation of clinical response and reduction in bacterial load (sputum colour and volume, systemic inflammation, pulmonary physiology and assessment of exercise capacity)
Measured: 21 days
Antibiotic side effects
Patients will be asked to report any side effects from the treatment and at what day these effects occurred.
Measured: 14 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jan 2014 (estimated)
- Study startJan 2014
- Primary completion1 Feb 2020
- Study completion1 Feb 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for BronchiectasisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 90 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Edinburgh
- Sponsor type
- University, hospital or other
- Collaborators
- NHS Lothian
- Responsible party
- Sponsor
- Investigators
- Adam T Hill, MBCHB, MRCP, MD, Principal investigator, NHS Lothian
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02047773
- Sponsor's protocol ID
- BLTBrIVStudy
- Acronym
- BLTBrIV
- Status last verified
- May 2020
- First submitted
- 22 Jan 2014
- Last updated
- 4 May 2020
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
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.
PubMed 36746812Bedi 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.
PubMed 34112732
Study at a glance
From the registry record, last updated by the sponsor on 4 May 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Bacterial Load Guided Therapy for Severe Exacerbations of Bronchiectasis Requiring IntraVenous Antibiotic Therapy- BLT Br IV Study
- ClinicalTrials.gov ID
- NCT02047773
- Acronym / sponsor ID
- BLTBrIV / BLTBrIVStudy
- Conditions
- Bronchiectasis
- Keywords
- bronchiectasis, intravenous antibiotics, duration of antibiotic course, side effects, bacterial load
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 90 participants (actual)
- Lead sponsor
- University of EdinburghUniversity, hospital or other
- Collaborators
- NHS Lothian
- Study start
- Jan 2014
- Primary completion
- 1 Feb 2020 (actual)
- Study completion
- 1 Feb 2020 (actual)
- First posted
- 28 Jan 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 14 days Duration | Placebo comparator | Drug: Colomycin14 days of antibiotics regardless of bacterial load. |
| Bacterial load guided duration | Active comparator | Other: Duration, Drug: Colomycin, Drug: MeropenemAntibiotics 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (11 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DurationIf 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. | Other | Bacterial load guided duration |
| ColomycinIf there is a clinical deterioration a second antibiotic to augment treatment (Colomycin) will be added for both arms of the study. | Drug | 14 days Duration, Bacterial load guided duration |
| Meropenem | Drug | Bacterial load guided duration |
Primary outcome
Time to next exacerbation
Time frame: up to 1 year following IV antibiotics
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).
Proportion of patients that stopped antibiotics early
Time frame: 14 days
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.
3 secondary outcomes
Clinical recovery at days 14 and 21
Time frame: 21 days
Correlation of bacterial load with clinical response
Time frame: 21 days
Antibiotic side effects
Time frame: 14 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 May 2020.
- Derived from this study: PubMed 36746812Hill 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.
- Derived from this study: PubMed 34112732Bedi 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Adam T Hill, MBCHB, MRCP, MD principal investigator
NHS Lothian
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Duration, Colomycin and Meropenem in people with Bronchiectasis, run by University of Edinburgh at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 May 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to next exacerbation (time frame: up to 1 year following IV antibiotics). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02047773, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 May 2020.