Chronic Obstructive Pulmonary Disease (COPD) MedDRA version: 20.0 Level: LLT Classification code 10010952 Term: COPD System Organ Class: 100000004855 MedDRA version: 20.0 Level: LLT Classification code 10010953 Term: COPD exacerbation System Organ Class: 100000004855
Conditions
Interventions
Trade Name: Bisoprolol
Product Name: Bisoprolol
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Bisoprolol fumarate
CAS Number: 104344-23-2
Concentration unit: mg milligram(s)
Concentrati
Sponsors
University of Aberdeen
NHS Grampian
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: -Aged = 40 years. -A smoking history of at least 10 pack years. -An established predominant diagnosis of COPD (NICE Guideline definition: post bronchodilator FEV1=65 years) yes F.1.3.1 Number of subjects for this age range 770
Exclusion criteria
Exclusion criteria: -A current sole respiratory diagnosis of asthma. -Any diagnosis of asthma before the age of 40 years. -A predominant respiratory disease other than COPD. -Any significant disease/disorder which, in the investigator’s opinion, either puts the patient at risk because of study participation or may influence the results of the study or the patient's ability to participate in the study. -Previous allocation of a randomisation code in the study or current participation in another interventional study (CTIMP or non-CTIMP). -Already taking beta-blocker. -Known or suspected hypersensitivity to beta-blocker. -For women, current pregnancy or breast-feeding, or planned pregnancy during the study. -Unable to perform spirometry (FEV1 manoeuvre). -Current resting (5 minutes sitting) heart rate <60 bpm. -Current resting (5 minutes sitting) systolic blood pressure <100mmHg. -2nd, 3rd degree heart block on ECG (unless pacemaker in situ). -Conditions for which beta-blocker use is a guideline recommendation, i.e. heart failure, or within the last year: myocardial infarction, acute coronary syndrome. -Current tachyarrythmia or bradyarrhythmia (including sick sinus syndrome, sinoatrial block) requiring treatment. -Current treatment with interacting drugs: o heart rate limiting drug such as calcium channel blockers (diltiazem, verapamil), ivabradine, o class-I antiarrhythmic drugs (e.g. quinidine, disopyramide; lidocaine, phenytoin; flecainide, propafenone), o centrally-acting antihypertensive drugs (e.g. clonidine methyldopa, moxonidine, rilmenidine). -Severe peripheral arterial occlusive disease, severe forms of Raynauds syndrome. -Conditions that are known to be triggered by beta-blockers or beta-blocker withdrawal including myasthenia gravis, periodic hypokalaemic paralysis, pheochromocytoma, thyrotoxicosis and psoriasis/history of psoriasis.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: The number of participant reported exacerbations of COPD requiring treatment with antibiotics and/or oral corticosteroids will be ascertained at the 26 and 52 week assessment visits.;Main Objective: The primary objective is to determine whether adding bisoprolol (maximum dose 5mg a day) to existing COPD treatment in patients who have chronic obstructive pulmonary disease will reduce the number of exacerbations (or flare ups) of the condition. If the treatment is effective, we will also assess whether it is cost effective;Secondary Objective: The secondary objectives are to compare the following outcomes between participants treated with bisoprolol, and those treated with placebo: -Hospital admissions with a primary diagnosis of COPD exacerbation. -Total number of emergency hospital admissions. -Total number of major adverse cardiovascular events (MACE). -Lung function. -Changes in breathlessness during treatment. -All-cause, respiratory and cardiac mortality. -Drug reactions and serious adverse events. -Health related quality of life. -Disease specific health status. -Health care utilisation. -Incremental cost-per-exacerbation avoided. -Costs to the NHS and patients and lifetime cost-effectiveness based on extrapolation modelling. -Modelled lifetime incremental cost per Quality Adjusted Life Year. -Treatment effects in participants with and without clinically diagnosed heart disease. ;Primary end point(s): The primary clinical outcome measure will be the total number of exacerbations of COPD necessitating changes in management (minimum management change use of oral corticosteroids and/or antibiotics) during the one year treatment period, as reported by the participant. The primary economic outcome measure will be cost per QALY gained during the one year treatment period. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): -Total number of COPD exacerbations requiring hospital admission*. -Time to first exacerbation of COPD. -Total number of emergency hospital admissions (all causes)*. -Total number of major adverse cardiovascular events (MACE) (defined by cardiovascular death, hospitalisation for myocardial infarction, heart failure, or stroke), percutaneous coronary intervention or coronary artery bypass grafting. -Lung function (FEV1, FVC) post bronchodilator using spirometry performed to ATS/ERS standards. -Breathlessness using Baseline and Transition Dyspnoea Indices (BDI & TDI). -All-cause, respiratory and cardiac mortality. -Serious adverse events, adverse reactions. -Health related quality of life using EuroQoL 5D (EQ-5D-5L) Index. -Disease specific health status using the COPD Assessment Test (CAT). -Utilisation of primary or secondary health care for respiratory events. -Change in disease associated symptoms using the Hull Airways Reflux Questionnaire (HARQ) [this will only be done at some recruitment sites]. -Modelled lifetime incremental cost per Quality Adjusted Life Year. ;Timepoint(s) of evaluation of this end point: These will be assessed at the 26 and 52 week assessment visits. | — |
Countries
United Kingdom
Outcome results
None listed