COPD Chronic Obstructive Pulmonary Disease MedDRA version: 16.1 Level: LLT Classification code 10010952 Term: COPD System Organ Class: 100000004855 MedDRA version: 16.1 Level: LLT Classification code 10010953 Term: COPD exacerbation System Organ Class: 100000004855
Conditions
Interventions
Trade Name: Doxycycline 100
Product Name: Doxycycline
Pharmaceutical Form: Capsule
INN or Proposed INN: Doxycycline
CAS Number: 564250
Sponsors
Imperial College London
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients eligible for enrolment in the study must meet all the following criteria: • Informed Consent: Patients must give their signed and dated written informed consent to participate • Confirmed COPD diagnosis (Post bronchodilator spirometry spirometry: FEV1/FVC=65 years) yes F.1.3.1 Number of subjects for this age range 172
Exclusion criteria
Exclusion criteria: • Patients with known active TB or other clinically significant chronic respiratory disease (e.g. chronic asthma, bronchiectasis, pulmonary fibrosis) in the judgment of the study doctor. • Hepatic or renal impairment as defined as LFTs > 5XULN, and creatinine > 5 x ULN. • Patients with known hypersensitivity to the IMP and/or Placebo including their excipients. • Patients taking ongoing antibiotic therapy for COPD or other conditions. • Patients with uncontrolled clinically significant hypertension • Female patients who are pregnant or planning on becoming pregnant during the study, or are breastfeeding. • Clinically relevant abnormal electrolyes (sodium or potassium), renal function (urea and creatinine) or liver function (ALT, AST, ALP) that could interfere with the objectives of the trial or safety of the volunteer • Patient taking clinically significant contraindicated medication, as per the SmPC for Doxycycline. • Use of another experimental investigational medicinal product within 3 months of study enrolment. If the IMP used was as part of the NIHR WP2 study then entry to WP3 after a 6 week washout period is permissible. • Patients with any other condition precluding enrolment in the trial, according to the assessment of the study doctor. This will be documented at screening. Females of childbearing potential must be willing to use an effective method of contraception from the time consent is signed until (6 weeks) after treatment discontinuation. These include: • Complete abstinence from screening to final visit • Male partner is sterile (vasectomy with documentation of azoospermia) prior to female subject entry into the study, and this male partner is the sole partner for the subject • Implants of levonorgestral inserted for at least 1 month prior to the study medication administration but not beyond the third successive year following insertion • Injectable progestogen administered for at least 1 month prior to study medication administration • Oral contraception (combined or progestogen only) administrated for at least one monthly cycle prior to study medication administration. • Double barrier methods: condoms or occlusive cap (diaphragm or cervical/vault caps) plus spermicidal agent (foam/get/film/cream/suppository) • An intrauterine device (IUD), inserted by a qualified physician, with published data showing that the highest expected failure rate is less than 1% per year • Estrogenic vaginal ring • Percutaneous contraceptive patches. Females of childbearing potential must have a negative pregnancy test within 7 days prior to receiving trial treatment. NOTE: Subjects are considered not of childbearing potential if they are surgically sterile (i.e. they have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are postmenopausal. Females must not be breastfeeding.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The principal research question/objective is to assess whether the use of an antibiotic for 12 months by a group of patients with COPD reduces their rate of COPD exacerbations (periodic flare-ups of COPD symptoms) compared to a control group, taking a placebo. ; Secondary Objective: To assess the effect of Doxycycline on on: • Changes in spirometry (lung function measure) from baseline • Changes in respiratory health status from baseline, as measured by St. Georges Respiratory Questionnaire (SGRQ). • Changes in COPD health status from baseline, as measured by COPD Assessment Test (CAT). • Changes in lower airway bacteria concentration (cfu/ml) from baseline and compare that to placebo. • To collect further data on cost-effectiveness of antibiotics in preventing exacerbations which will be evaluated in a future work package(WP5). This includes EQ5D and SF12 questionnaires. • To collect further data on patient adherence to be analysed in as part of a future work package (WP6) (Questionnaires to include BMQ-12 general and BMQ-specific scale, PSM, MARS, AP-6/12). • Patient adherence to antibiotic/placebo treatment as measured by diary cards and pill counts at treatment end. • Changes in CRP levels (a systemic inflammatory marker, shown to be associated with ;Primary end point(s): The primary outcome will be the rate of exacerbations (COPD symptom flare ups) per person-year recorded from the date of drug issue until the date of end of treatment visit. Patients will be considered to not be at-risk of a repeat exacerbation until they have recovered from their most recent exacerbation and are no longer in the post-recovery period. The difference in exacerbation rate per person-year between the active treatment and control group will be analysed using zero inflated Poisson or negative binomial regression, | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Lung function (spirometry) (FEV1, FVC, FEV1/FVC ratio, FEV1 as % Predicted). • Total and individual component(symptoms, activity, impact) SGRQ scores will be used to measure health status. Each range from zero (no impairment) to 100 (maximum impairment). • Respiratory health status across groups as measured from total number of symptoms in a day and prevalence of individual symptoms recorded on daily diary cards. • Airway bacteria numbers taken from a sputum sample, provided by a subset of patients, at months 3, 6, 9, 12 after drug issue. Sputum samples will be collected and analysed using routine culture methods, together with evaluation of any bacterial resistance by susceptibility testing. • CRP - changes in CRP levels from baseline. • Hospital admissions. This data will be collected from HES. • Time to 1st exacerbation measured by diary cards in both therapy and placebo groups. • Rate of exacerbations treated with steroids and antibiotics. • Adherence as measured using pill counts. • Antibiotic resistance measured in the subset of patients (able to produce sputum) from sputum based on standard NHS procedures (not resistant, intermediate, severe, resistant). ;Timepoint(s) of evaluation of this end point: 12 months. | — |
Countries
United Kingdom
Outcome results
None listed