Beta-blockeRs tO patieNts with CHronIc Obstructive puLmonary diseasE (BRONCHIOLE) - Study protocol from a randomized controlled trial

Josefin Sundh, Anders Magnuson, Scott Montgomery, Pontus Andell, Gustaf Rindler, Ole Fröbert, BRONCHIOLE investigators, Malgorzata Przybyszewska, Anders Blomberg, Magnus Widmark, Andreas Palm, Wolfgang Greger, Jens Ellingsen, Lennart Råhlén, Taivo Kipper, Mikael Hasselgren, Carolina Smith, Florim Delijaj, Kaj Possler, Johanna Nilsson, Niklas Stenersen, Han Nguyen, Dan Curiac, Lowie E G W Vanfleteren, Lars Johansson, Folke Sjöberg, Magnus Ekström, Johan Sanmartin Berglund, Anders Lökke, Josefin Sundh, Anders Magnuson, Scott Montgomery, Pontus Andell, Gustaf Rindler, Ole Fröbert, BRONCHIOLE investigators, Malgorzata Przybyszewska, Anders Blomberg, Magnus Widmark, Andreas Palm, Wolfgang Greger, Jens Ellingsen, Lennart Råhlén, Taivo Kipper, Mikael Hasselgren, Carolina Smith, Florim Delijaj, Kaj Possler, Johanna Nilsson, Niklas Stenersen, Han Nguyen, Dan Curiac, Lowie E G W Vanfleteren, Lars Johansson, Folke Sjöberg, Magnus Ekström, Johan Sanmartin Berglund, Anders Lökke

Abstract

Background: Observational studies indicate that beta-blockers are associated with a reduced risk of exacerbation and mortality in patients with chronic obstructive pulmonary disease (COPD) even without overt cardiovascular disease, but data from randomized controlled trials (RCT) are lacking. The aim of this RCT is to investigate whether beta-blocker therapy in patients with COPD without diagnosed cardiovascular disease is associated with a decreased 1-year risk of the composite endpoint of death, exacerbations, or cardiovascular events.

Methods: The Beta-blockeRs tO patieNts with CHronIc Obstructive puLmonary diseasE (BRONCHIOLE) study is an open-label, multicentre, prospective RCT. A total of 1700 patients with COPD will be randomly assigned to either standard COPD care and metoprolol at a target dose of 100 mg per day or to standard COPD care only. The primary endpoint is a composite of death, COPD exacerbations, and cardiovascular events. Major exclusion criteria are ischemic heart disease, left-sided heart failure, cerebrovascular disease, critical limb ischemia, and atrial fibrillation/flutter. Study visits are an inclusion visit, a metoprolol titration visit at 1 month, follow-up by telephone at 6 months, and a final study visit after 1 year. Outcome data are obtained from medical history and record review during study visits, as well as from national registries.

Discussion: BRONCHIOLE is a pragmatic randomized trial addressing the potential of beta-blockers in patients with COPD. The trial is expected to provide relevant clinical data on the efficacy of this treatment on patient-related outcomes in patients with COPD.

Trial registration: ClinicalTrials.gov, ID: NCT03566667. Registered on 25 June 2018.

Keywords: Beta-blocker; COPD; Cardiovascular event; Exacerbation; Mortality; Pragmatic randomized trial; Real-world evidence.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
SPIRIT Figure of the trial procedure, including enrolment, data collection, interventions and assessments. COPD staging is performed as GOLD stage I–IV based on FEV1%pred and GOLD group A-D based on exacerbation frequency and CAT score [25]. Maintenance treatment includes COPD and cardiovascular treatment in the following groups: Long-acting muscarinic antagonists; long-acting beta-2-agonists; inhaled corticosteroids; roflumilast; long-term oxygen therapy; other COPD treatment, including azithromycin and teofyllamin; ACE/AII-inhibitors; calcium-inhibitors; diuretics; and class I–IV anti-arrhythmics. BP blood pressure, CAT COPD Assessment Test, COPD chronic obstructive pulmonary disease, ECG electrocardiography, FEV1 forced expiratory volume in 1 s, GOLD Global initiative for Obstructive Lung Disease, HR heart rate

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