预防慢性阻塞性肺疾病（COPD）中的不良心脏事件（PACE）：双盲、安慰剂对照、随机对照试验中比索洛尔在 COPD 中的应用研究方案。

Preventing adverse cardiac events (PACE) in chronic obstructive pulmonary disease (COPD): study protocol for a double-blind, placebo controlled, randomised controlled trial of bisoprolol in COPD.

机构信息

The George Institute for Global Health, Newtown, New South Wales, Australia

University of New South Wales, Sydney, New South Wales, Australia.

出版信息

BMJ Open. 2021 Aug 27;11(8):e053446. doi: 10.1136/bmjopen-2021-053446.

DOI:10.1136/bmjopen-2021-053446

PMID:34452971

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8404458/

Abstract

INTRODUCTION

Heart disease in chronic obstructive pulmonary disease (COPD) is a common but neglected comorbidity. Patients with COPD are frequently excluded from clinical trials of treatments aimed at reducing cardiac morbidity and mortality, which has led to undertreatment of cardiovascular disease in patients with COPD. A particular concern in COPD is the underuse of beta (β)-blockers. There is observational evidence that cardioselective β-blockers are safe and may even reduce mortality risk in COPD, although some evidence is conflicting. There is an urgent need to answer the research question: Are cardioselective β-blockers safe and of benefit in people with moderately severe COPD? The proposed study will investigate whether cardioselective β-blocker treatment in patients with COPD reduces mortality and cardiac and respiratory morbidity.

METHODS AND ANALYSES

This is a double-blind, randomised controlled trial to be conducted in approximately 26 sites in Australia, New Zealand, India, Sri Lanka and other countries as required. Participants with COPD will be randomised to either bisoprolol once daily (range 1.25-5 mg, dependent on tolerated dose) or matched placebo, in addition to receiving usual care for their COPD over the study duration of 24 months.The study will enrol 1164 participants with moderate to severe COPD, aged 40-85 years. Participants will be symptomatic from their COPD and have a postbronchodilator forced expiratory volume in 1 s (FEV) ≥30% and ≤70% predicted and a history of at least one exacerbation requiring systemic corticosteroids, antibiotics or both in the prior 24 months.

ETHICS AND DISSEMINATION

The study protocol has been approved by the Sydney Local Health District Human Research Ethics Committee at The Concord Repatriation General Hospital.

TRIAL REGISTRATION NUMBERS

NCT03917914; CTRI/2020/08/027322.

摘要

简介

慢性阻塞性肺疾病（COPD）患者常合并心脏病，但这一合并症常被忽视。COPD 患者经常被排除在旨在降低心脏发病率和死亡率的治疗临床试验之外，这导致 COPD 患者的心血管疾病治疗不足。COPD 中特别值得关注的是β（β）-受体阻滞剂使用不足。有观察性证据表明，心脏选择性β-受体阻滞剂是安全的，甚至可能降低 COPD 患者的死亡风险，但也有一些证据存在争议。目前迫切需要回答研究问题：心脏选择性β-受体阻滞剂在中度严重 COPD 患者中是否安全且有益？拟议的研究将调查 COPD 患者的心脏选择性β-受体阻滞剂治疗是否降低死亡率以及心脏和呼吸系统发病率。

方法和分析

这是一项在澳大利亚、新西兰、印度、斯里兰卡和其他国家的大约 26 个地点进行的双盲、随机对照试验。将招募患有 COPD 的患者，将其随机分为每天服用比索洛尔（范围 1.25-5mg，取决于可耐受的剂量）或匹配安慰剂组，同时在 24 个月的研究期间接受 COPD 的常规治疗。该研究将招募 1164 名患有中重度 COPD 的患者，年龄在 40-85 岁之间。参与者因 COPD 而出现症状，支气管扩张剂后用力呼气量 1 秒（FEV）≥30%且≤70%预计值，并且在过去 24 个月内至少有一次需要全身皮质类固醇、抗生素或两者联合治疗的加重。