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Rationale and Design of Low-dose Administration of Carperitide for Acute Heart Failure (LASCAR-AHF)

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Abstract

Backgrounds

Despite current therapies, acute heart failure (AHF) remains a major public health burden with high rates of in-hospital and post-discharge morbidity and mortality. Carperitide is a recombinantly produced intravenous formulation of human atrial natriuretic peptide that promotes vasodilation with increased salt and water excretion, which leads to reduction of cardiac filling pressures. A previous open-label randomized controlled study showed that carperitide improved long-term cardiovascular mortality and heart failure (HF) hospitalization for patients with AHF, when adding to standard therapy. However, the study was underpowered to detect a difference in mortality because of the small sample size.

Methods

Low-dose Administration of Carperitide for Acute Heart Failure (LASCAR-AHF) is a multicenter, randomized, open-label, controlled study designed to evaluate the efficacy of intravenous carperitide in hospitalized patients with AHF. Patients hospitalized for AHF will be randomly assigned to receive either intravenous carperitide (0.02 μg/kg/min) in addition to standard treatment or matching standard treatment for 72 h. The primary end point is death or rehospitalization for HF within 2 years. A total of 260 patients will be enrolled between 2013 and 2018.

Conclusion

The design of LASCAR-AHF will provide data of whether carperitide reduces the risk of mortality and rehospitalization for HF in selected patients with AHF.

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Acknowledgements

The authors are grateful for the contributions of all the investigators, clinical research coordinators, data managers, and laboratory technicians involved in the LASCAR-AHF study.

Funding

The LASCAR-AHF study was supported by grants from the Japan Research Foundation for Clinical Pharmacology (T Nagai) and the Japan Cardiovascular Research Foundation (29-4-3, T Anzai).

Author information

Author notes

  1. Yasuyuki Honda and Hiroki Nakano contributed equally to this work.

Authors and Affiliations

  1. Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan

    Toshiyuki Nagai, Yasuyuki Honda, Hiroki Nakano, Satoshi Honda, Naotsugu Iwakami, Yasuhide Asaumi, Yoshio Tahara, Takeshi Aiba, Yasuo Sugano, Hideaki Kanzaki, Teruo Noguchi, Kengo Kusano, Satoshi Yasuda, Hisao Ogawa & Toshihisa Anzai

  2. National Heart and Lung Institute, Imperial College London, Emmanuel Kaye Building, Manresa Road, London, SW3 6LR, UK

    Toshiyuki Nagai

  3. Department of Cardiology, St. Luke’s International Hospital, Tokyo, Japan

    Atsushi Mizuno & Nobuyuki Komiyama

  4. Department of Cardiovascular Medicine, Kobe City Medical Center General Hospital, Kobe, Japan

    Takafumi Yamane & Yutaka Furukawa

  5. Division of Cardiology, Department of Medicine, Okinawa Chubu Hospital, Okinawa, Japan

    Tadayoshi Miyagi

  6. Department of Cardiology, Tokyo Medical University Hachioji Medical Center, Tokyo, Japan

    Syuzo Nishihara & Nobuhiro Tanaka

  7. Department of Cardiovascular Medicine, National Hospital Organization Tochigi Medical Center, Tochigi, Japan

    Taichi Adachi

  8. Department of Data Science, National Cerebral and Cardiovascular Center, Osaka, Japan

    Toshimitsu Hamasaki

  9. Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan

    Toshihisa Anzai

Authors
  1. Toshiyuki Nagai
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  2. Yasuyuki Honda
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Contributions

T Nagai and T Anzai conceived of the study and wrote the manuscript and are the grant holders. YH, HN, SH, NI, AM, NK, TY, YF, TM, SN, NT, T Adachi, YA, YT, T Aiba, YS, and HK conceived of and coordinated the study. TH provided the statistical inputs to the study design and protocol. T Noguchi, KK, SY, and HO conceived of and supervised the study. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Toshiyuki Nagai.

Ethics declarations

Before enrollment of the patients, the study protocol will be approved by each institutional review board of all participating centers. This study complies with the Declaration of Helsinki. Written informed consent will be obtained from all patients before they are recruited. Personal information about potential and enrolled participants will remain confidential, and data will be de-identified using participant numbers.

Conflict of Interest

T Nagai received a research grant for studying abroad from the Daiichi Sankyo Foundation of Life Science. T Aiba received a research grant from the Daiichi Sankyo Co, Ltd.

Availability of Data and Materials

To avoid bias of the analysis, the dataset supporting the conclusions of this article will not be available until the final report of this trial is published.

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Nagai, T., Honda, Y., Nakano, H. et al. Rationale and Design of Low-dose Administration of Carperitide for Acute Heart Failure (LASCAR-AHF). Cardiovasc Drugs Ther 31, 551–557 (2017). https://doi.org/10.1007/s10557-017-6760-z

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