Chronic Obstructive Pulmonary Disease (COPD)
Conditions
Keywords
Chronic Obstructive Pulmonary Disease (COPD)
Brief summary
This study investigates the effects of targeted re-treatment of patients who do not recover from an exacerbation of COPD. Half of the patients will receive ciprofloxacin while the other half will receive a placebo.
Detailed description
COPD is a long term lung condition where patients suffer recurrent symptom flare-ups, called 'exacerbations'. Patients who have lots of exacerbations have a worse quality of life, poorer ability to breath, and may die earlier than those who don't. Previous research by our group has shown that patients who have an exacerbation and have not completely recovered two weeks after the start of treatment are more likely to suffer another one early than those who completely recover. This study aims to test whether we can prevent this early re-exacerbation by giving an extra course of antibiotics, compared to a placebo. Patients who experience an exacerbation of COPD and are treated with antibiotics will, two weeks after the start of their treatment, be invited to attend a screening visit. Patients will be eligible for the study if they have not fully recovered at this visit (i.e. if they either still have symptoms or if blood tests show there is still inflammation present) and fulfil other diagnostic measures for COPD. Patients will be allocated to the treatment groups at random, and if eligible will be treated with a further 1 week of ciprofloxacin 500mg twice daily or a placebo. Patients will then be followed up in the study for a further 3 months, and the primary study outcome will be the time to the next exacerbation.
Interventions
DRUGCiprofloxacin
500 mg, twice daily for 1 week (oral)
DRUGPlacebo
One capsule, twice daily for 1 week
Sponsors
Imperial College London
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
45 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Diagnosis of COPD confirmed spirometrically at screening 2. COPD exacerbation with treatment commenced 14 days prior to study enrolment and treated with 5-14 days of a non-quinolone antibiotic. 3. Exacerbation here will be defined as an episode of symptomatic worsening of COPD that was treated by the patient's attending clinician. Confirmation of the initial exacerbation diagnosis will be provided from the case notes, referral letter, or directly from the treating clinician, and will be documented in the CRF. 4. Age: ≥ 45 years of age at screening. 5. Persistent symptoms and/or a CRP≥8mg/L when assessed 2 weeks after exacerbation onset 6. Able to complete questionnaires for health status and symptoms and keep written diary cards 7. Severity of disease: Patients with a measured FEV1\<80% of predicted normal values at 2 weeks post exacerbation 8. Able and willing to give signed and dated written informed consent to participate.
Exclusion criteria
1. Other clinically predominant chronic respiratory disease. 2. Intubated and receiving mechanical ventilation 3. Patients with known hypersensitivity to the antibiotic under evaluation, to other quinolones or any excipients of the IMP/placebo. 4. Patients with a prior history of tendonopathy or tendon rupture 5. Elderly patients taking long term systemic corticosteroids 6. Patients on long term antibiotics for other conditions 7. Patient too unwell for randomisation, i.e. requiring retreatment in the judgment of the study doctor 8. Female patients who are pregnant or planning on becoming pregnant during the study, or are breastfeeding. 9. Patient taking clinically significant contraindicated medication as per the SmPC s, such as use of concomitant tizanidine or methotrexate.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to the Next COPD Exacerbation | Up to 90 days | The primary outcome will be the time to the next COPD exacerbation following targeted retreatment with the IMP or placebo, censored at 90 days. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of the Initial Exacerbation | Up to 90 days | Secondary endpoints will include duration of the initial exacerbation following targeted retreatment with the IMP or placebo. |
| Number of Participants With Serious Non Fatal Adverse Events | 7 days of treatment | Secondary endpoints will include adverse events following targeted retreatment with the IMP or placebo. |
| Changes in Lung Function | Baseline and 90 days | Secondary endpoints will include changes from randomization to 90 days in FEV1. |
| Number of Participants Who Have Resistance Bacteria in the Sputum | Up to 90 days | Bacterial load and resistance Secondary endpoints will include resistance following targeted retreatment with the IMP or placebo. |
| Hospital Readmission | 90 days of treatment | Secondary endpoints will include hospital readmission following targeted retreatment with the IMP or placebo. |
Countries
United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ciprofloxacin 500 mg, twice daily for 1 week (oral).
Ciprofloxacin: 500 mg, twice daily for 1 week (oral) | 72 |
| Placebo one capsule, twice daily for 1 week.
Placebo: One capsule, twice daily for 1 week | 72 |
| Total | 144 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 |
| Overall Study | Death | 1 | 1 |
| Overall Study | Did not tolerate IMP | 0 | 1 |
| Overall Study | Lost to Follow-up | 1 | 2 |
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 2 |
Baseline characteristics
| Characteristic | Placebo | Total | Ciprofloxacin |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 52 Participants | 107 Participants | 55 Participants |
| Age, Categorical Between 18 and 65 years | 20 Participants | 37 Participants | 17 Participants |
| Age, Continuous | 69.1 years STANDARD_DEVIATION 7.4 | 69.1 years STANDARD_DEVIATION 8.1 | 69.1 years STANDARD_DEVIATION 8.8 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) White | 69 Participants | 138 Participants | 69 Participants |
| Region of Enrollment United Kingdom | 72 participants | 144 participants | 72 participants |
| Sex: Female, Male Female | 25 Participants | 53 Participants | 28 Participants |
| Sex: Female, Male Male | 47 Participants | 91 Participants | 44 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 72 | 1 / 72 |
| other Total, other adverse events | 12 / 72 | 8 / 72 |
| serious Total, serious adverse events | 1 / 72 | 9 / 72 |
Outcome results
Primary
Time to the Next COPD Exacerbation
The primary outcome will be the time to the next COPD exacerbation following targeted retreatment with the IMP or placebo, censored at 90 days.
Time frame: Up to 90 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ciprofloxacin | Time to the Next COPD Exacerbation | 72 days |
| Placebo | Time to the Next COPD Exacerbation | 58 days |
Comparison: The primary endpoint was assessed using a Cox's proportional hazard model with pre-specified adjustment for patient's self-reported history of exacerbations over the previous year and with stratification for study centre. The onset of exacerbation will be monitored up to 90 days or at patient withdrawal.p-value: 0.76495% CI: [0.684, 1.676]Regression, Cox
Secondary
Changes in Lung Function
Secondary endpoints will include changes from randomization to 90 days in FEV1.
Time frame: Baseline and 90 days
Population: Only the participants who completed the study
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ciprofloxacin | Changes in Lung Function | 0.0229 litres | Standard Deviation 0.199 |
| Placebo | Changes in Lung Function | 0.0041 litres | Standard Deviation 0.198 |
p-value: 0.239t-test, 2 sided
Secondary
Duration of the Initial Exacerbation
Secondary endpoints will include duration of the initial exacerbation following targeted retreatment with the IMP or placebo.
Time frame: Up to 90 days
Population: Missing participants data 16 for ciprofloxacin and 15 for placebo
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ciprofloxacin | Duration of the Initial Exacerbation | 3 days |
| Placebo | Duration of the Initial Exacerbation | 4 days |
p-value: 0.703Wilcoxon (Mann-Whitney)
Secondary
Hospital Readmission
Secondary endpoints will include hospital readmission following targeted retreatment with the IMP or placebo.
Time frame: 90 days of treatment
Population: Data not collected
Secondary
Number of Participants Who Have Resistance Bacteria in the Sputum
Bacterial load and resistance Secondary endpoints will include resistance following targeted retreatment with the IMP or placebo.
Time frame: Up to 90 days
Population: Lower participants number due to the number of patients with a pathogenic organism with newly acquired ciprofloxacin resistance, present in a sputum sample collected at 90 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ciprofloxacin | Number of Participants Who Have Resistance Bacteria in the Sputum | 0 Participants |
| Placebo | Number of Participants Who Have Resistance Bacteria in the Sputum | 1 Participants |
Secondary
Number of Participants With Serious Non Fatal Adverse Events
Secondary endpoints will include adverse events following targeted retreatment with the IMP or placebo.
Time frame: 7 days of treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ciprofloxacin | Number of Participants With Serious Non Fatal Adverse Events | 1 Participants |
| Placebo | Number of Participants With Serious Non Fatal Adverse Events | 9 Participants |