Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Apr 12;7(5):383-388.
doi: 10.1253/circrep.CR-25-0010. eCollection 2025 May 9.

Rationale and Design of an Exploratory, Randomized, Open-Label, Multicenter Clinical Trial to Investigate the Efficacy of Long-Acting β2-Agonist/Long-Acting Muscarinic Antagonist on Heart Failure Complicated by Chronic Obstructive Pulmonary Disease (COPD-HF Trial)

Hiroya Hayashi  1   2 , Shin Ito  3   4 , Hiroki Fukuda  5 , Makoto Sata  6 , Yukio Abe  7 , Kohei Fujimoto  8 , Daiju Fukuda  2 , Yohei Hanajima  9 , Mutsuo Horii  9 , Noriyuki Ikehara  10 , Moriaki Inoko  5 , Chisato Izumi  4 , Yasuhiro Izumiya  2   11 , Takafumi Nakayama  10   12 , Takashi Sozu  13 , Shigeru Toyoda  14 , Masafumi Watanabe  15 , Masashi Yokoi  12 , Masafumi Kitakaze  16   17   18
Affiliations

Rationale and Design of an Exploratory, Randomized, Open-Label, Multicenter Clinical Trial to Investigate the Efficacy of Long-Acting β2-Agonist/Long-Acting Muscarinic Antagonist on Heart Failure Complicated by Chronic Obstructive Pulmonary Disease (COPD-HF Trial)

Hiroya Hayashi et al. Circ Rep. .

Abstract

Background: Chronic obstructive pulmonary disease (COPD) is one of the most common comorbidities in patients with chronic heart failure (CHF). A growing number of patients are suffering from both COPD and CHF, and these conditions worsen each other. Inhaled bronchodilator therapy with long-acting muscarinic antagonist (LAMA) and long-acting β2-agonist (LABA) in combination is currently the mainstay of treatment for COPD. However, the effect of LAMA/LABA on HF with COPD remains unknown.

Methods and results: The COPD-HF trial is a multicenter, double-arm, open-label, exploratory, investigator-initiated clinical study to investigate the effect of LAMA/LABA on HF in patients suffering from both COPD and CHF. The participants are randomly assigned (1 : 1) to the LAMA/LABA (tiotropium+olodaterol FDC (fixed-dose combination) 5/5 ug) group (once a day, 2 inhalations) or non-pharmacological treatments for COPD as a control group. The planned number of patients to be enrolled in this trial is 54 in total (27 in each group). The participants are followed up for 12 weeks with and without LAMA/LABA. The primary endpoint is the change in plasma B-type natriuretic peptide levels from the baseline to the end of this study (12 weeks).

Conclusions: The COPD-HF trial will investigate the efficacy of LAMA/LABA on HF in patients with COPD and CHF.

Keywords: Chronic heart failure (CHF); Chronic obstructive pulmonary disease (COPD); Long-acting muscarinic antagonist/long-acting β2-agonist (LAMA/LABA).

PubMed Disclaimer

Conflict of interest statement

Boehringer Ingelheim Co. will not have any role in the analysis or interpretation of the results of this study. H.H., S.I., H.F., M.S., Y.A., K.F., D.F., Y.H., M.H., N.I., M.I., Y.I., T.N., T.S., S.T., M.Y. and M.K. have nothing to disclose. C.I. and M.W. reports speaker honoraria from Nippon Boehringer Ingelheim, outside the submitted work. S.I. is a member of the Editorial Team of Circulation Reports.

Figures

Figure 1.
Figure 1.
Study design of the COPD-HF trial. COPD, chronic obstructive pulmonary disease; FDC, fixed-dose combination; LAMA/LABA, long-acting muscarinic antagonist/long-acting β2-agonist.
Figure 2.
Figure 2.
Schedule of enrolment, interventions and assessments. All study visits will occur during routine clinical follow-up visits. ※1The value of visit 1 can be substituted. ※2Add BNP to the measurement items. BNP, B-type natriuretic peptide; CAT, COPD assessment test; CBC, complete blood count; CHF, chronic heart failure; COPD, chronic obstructive pulmonary disease; CRP, C-reactive protein; IL-6, interleukin-6; KCCQ, Kansas City Cardiomyopathy Questionnaire; mMRC, modified Medical Research Council Dyspnea Scale; NYHA, New York Heart Association; TNF-α, tumor necrosis factor-α.
See this image and copyright information in PMC

References

    1. Go AS, Mozaffarian D, Roger VL, Benjamin EJ, Berry JD, Borden WB, et al.. Heart disease and stroke statistics – 2013 update: A report from the American Heart Association. Circulation 2013; 127: e6–e245. - PMC - PubMed
    1. Hawkins NM, Virani S, Ceconi C.. Heart failure and chronic obstructive pulmonary disease: The challenges facing physicians and health services. Eur Heart J 2013; 34: 2795–2803. - PubMed
    1. Hayashi H, Fukuda H, Hasegawa T, Takahama H, Amaki M, Kanzaki H, et al.. Impact of comorbidity of chronic obstructive pulmonary disease on cardiovascular events and prognosis in patients with chronic heart failure: A single-center retrospective observational study. Int J Gerontol 2020; 14: 298–303.
    1. Kato M, Komamura K, Kitakaze M, Hirayama A.. The impact of bronchodilator therapy on systolic heart failure with concomitant mild to moderate COPD. Diseases 2017; 6: 4. - PMC - PubMed
    1. Agusti A, Celli BR, Criner GJ, Halpin D, Anzueto A, Barnes P, et al.. Global initiative for chronic obstructive lung disease 2023 Report: GOLD Executive Summary. Eur Respir J 2023; 61: 2300239. - PMC - PubMed