Inhaled Bronchodilators to support the use of Beta-Blockers in Chronic Obstructive Pulmonary Disease (COPD).
The LABA/LAMA and beta-blocker regimen in COPD: the effect of combination umeclidinium/vilanterol (Anoro®/Ellipta®) therapy on FEV1, exercise tolerance, and broncho-protection in COPD.
Waikato District Health Board
36 participants
Dec 1, 2021
Interventional
Conditions
Summary
Beta-blocker therapy has been shown to markedly reduce the risk of mortality in patients with cardiovascular disease but are withheld to patients with COPD because of concerns that they may worsen airways disease. We want to study whether giving a combination of Long-Acting Muscarinic Antagonist (LAMA used to treat the symptoms of COPD such wheezing, coughing and shortness of breath ) and Long-acting bronchodilator inhalers (LABAs relax the muscles around your airways to help keep your airways open) can prevent any potential negative effects of beta-blockers on the lungs of people with COPD.
Eligibility
Inclusion Criteria7
- Physician diagnosis of COPD
- Post-bronchodilator FEV1/FVC <0.70
- Post-bronchodilator FEV1 between 30% and 80% of predicted
- Minimum 10 pack-year smoking history
- Age 40 years and over
- BP and spirometry criteria must be met after test dose of carvedilol
- Written informed consent
Exclusion Criteria22
- Self-reported diagnosis of asthma
- Post-bronchodilator improvement in FEV1 >400ml
- Lower respiratory tract infection within the previous 8 weeks
- COPD not clinically stable/COPD exacerbation within previous 8 weeks
- Requiring home oxygen/resting O2 saturations <90% on air when stable
- Currently in the acute phase of a pulmonary rehabilitation program
- Previously recorded allergy or intolerance of beta-blockers or any anticholinergic/muscarinic receptor antagonist, symp, lactose/milk protein or magnesium stearate
- Frequent episodes of hypoglycaemia (in patients with Diabetes Mellitus)
- Pregnancy & breastfeeding
- Concurrent use of other rate-limiting medication (e.g. rate-limiting calcium channel blockers)
- Already taking beta-blocker treatment
- Uncontrolled Heart Failure
- Systolic Blood Pressure less or equal to 110mmHg or >180mmHg at time of screening
- Diastolic blood pressure >100mmHg
- Bradycardia defined as <60bpm at time of screening
- Persistent tachyarrhythmia, including atrial fibrillation rate >120bpm
- Pre-existing 2nd/3rd degree AV-block
- Clinical instability or major cardiac event in the previous 12 weeks
- Severe Peripheral Vascular Disease
- Severe or unstable liver disease
- Acute angle closure glaucoma
- Any other condition, at the discretion of the investigator, which may impact on the safety of participants or feasibility of study results
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Interventions
RESPONSE: Doubling the dose has been explained in following the text from the protocol page 6, Telephone Call: "One week after starting each treatment, participants will be contacted by telephone to enquire about possible adverse effects to the study medication including dizziness/light-headedness, falls, worsening of respiratory symptoms. If necessary a clinic visit will be arranged to assess these symptoms. If no symptoms or only minor symptoms have been reported, the participants is willing and it is judged safe to increase the beta-blocker dose, participants will be instructed to double the dose of beta-blocker (taking 2 tablets each morning). If there are concerns about increasing the dose, but the participant is willing to continue in the study, the same dose can be continued (i.e. 2.5mg bisoprolol, 12.5mg carvedilol or matching placebo)." Eligible participants will undergo baseline measurements before an open-label test dose of ß–blocker (carvedilol 12.5mg). Participants who tolerate the test dose will be randomised to one of 6 treatment regimens, a. Placebo inhaler and placebo tablet b. Placebo inhaler and carvedilol 12.5mg/25mg c. Placebo inhaler and bisoprolol 2.5mg/5mg d. Umeclidinium/vilanterol 62.5/25mcg inhaler and placebo tablet e. Umeclidinium/vilanterol 62.5/25mcg inhaler and carvedilol 12.5mg/25mg f. Umeclidinium/vilanterol 62.5/25mcg inhaler and bisoprolol 2.5mg/5mg Treatment (inhaler and tablet) will be administered once per day in the morning. Each treatment arm lasts for 14 days, however 7 days after starting each treatment, participants will be contacted by telephone to enquire about possible adverse effects to the study medication including dizziness/light-headedness, falls, worsening of respiratory symptoms. If necessary a clinic visit will be arranged to assess these symptoms. If no symptoms or only minor symptoms have been reported, the participant is willing and it is judged safe to increase the beta-blocker dose, participants will be instructed to double the dose of beta-blocker (taking 2 tablets each morning). If there are concerns about increasing the dose, the participant may continue in the study at the same dose (i.e. 2.5mg bisoprolol, 12.5mg carvedilol or matching placebo) at the discretion of the PI and / or the participant is willing to continue. There will be no washout periods between each arm. Randomised participants will receive the next treatment pack in a consecutive sequence prepared in accordance with the randomisation schedule. Participants and Investigators will be blinded to the intervention order in the cross-over trial. All investigational drugs will be placebo-matched so the participant and investigators are unaware of the active drugs. At each treatment arm visit, participants will return ALL their study medication for compliance and reconciliation. Safety procedures will include spirometry testing (1, 2 and 3 hrs post dose), ECG, BP and 6 minute walk test (between 2 and 3 hours post dose). A questionnaire will be completed to reflect the symptoms of the last week. After completing all 6 treatment arms, the study will be complete.
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ACTRN12621001503819