Elsevier

American Heart Journal

Volume 244, February 2022, Pages 86-93
American Heart Journal

Trial Designs
Intravenous nicorandil during primary percutaneous coronary intervention in patients with ST-Elevation myocardial infarction: Rationale and design of the Clinical Efficacy and Safety of Intravenous Nicorandil (CLEAN) trial

https://doi.org/10.1016/j.ahj.2021.11.005Get rights and content

Background

The efficacy and safety of intravenous infusion of nicorandil during primary percutaneous coronary intervention (PCI) in patients with ST-elevation myocardial infarction (STEMI) remain uncertain.

Objectives

The primary objective of the CLinical Efficacy and sAfety of intravenous Nicorandil (CLEAN) trial is to evaluate the long-term efficacy and safety of intravenous administration of nicorandil as adjuncts to reperfusion therapy in patients with STEMI undergoing primary PCI.

Design

The CLEAN trial is a multicenter, randomized, double-blind, placebo-controlled trial that will enroll 1,500 patients from 40 centers across china. patients were randomly (1:1) assigned to receive intravenous nicorandil (6 mg as a bolus before reperfusion, followed by 48 hours of continuous infusion at a dose of 6 mg/h after coronary intervention) or the same dose of placebo according to randomization. The primary efficacy outcome was a composite of death from cardiovascular causes, nonfatal myocardial infarction, target vessel revascularization, and unplanned hospitalization for heart failure within 12 months. The secondary efficacy outcomes included the individual components of the combined efficacy endpoint, incidence of slow coronary flow after PCI, and incidence of complete ST-segment resolution at 2 hours after PCI. the safety outcomes included the incidence of hypotension after drug infusion and other adverse events during medication.

Summary

CLEAN will determine whether the addition of intravenous nicorandil as adjuncts to reperfusion therapy reduces the major adverse cardiovascular events in STEMI patients undergoing primary PCI.

Trial registration

ClinicalTrials.gov, NCT04665648

Section snippets

Trial Design

The CLEAN trial is an investigator-initiated, multicenter, randomized, double-blind, placebo-controlled study to determine the efficacy and safety of intravenous nicorandil as adjuncts to reperfusion therapy during primary PCI in patients with STEMI, which will recruit 1,500 patients in 40 sites across China. Recruitment was competitive with no maximum limit for patients from each center.

Eligibility

Male and female patients, aged ≥18 years and <80 years, with STEMI within 12 hours of symptom onset, were

Funding and Trial Oversight

This is an investigator-initiated study with financial support from the National Key Research and Development Program of China (grant number: 2016YFC1301203), funded by the Ministry of Science and Technology of the People's Republic of China. Sihuan Kebao Pharmaceutical (Beijing, China) provided the study drugs and placebos. The sponsor's role includes study design, overseeing, logistic support, and reviewing the reports of the study. The study protocol and other associated documents were

Ethics and Dissemination

The study fully adheres to the ethical principles of the Declaration of Helsinki, the specifications of the International Conference of Harmonization and Good Clinical Practice. The study protocol was approved by an independent ethics committee or institutional review board at each site.

Informed consent and detailed information about the study will be provided to all the patients before randomization. All the data in this trial are encrypted and stored in an online database accessible only to

Discussion

Nicorandil can not only effectively induce the dilatation of small vessels (<100 um) and increase coronary blood flow, but also prevents reperfusion injury and protects the heart against ischemic injury. Recent clinical trials have reported that nicorandil has beneficial effects as an adjunctive therapy for patients with ischemic heart disease, including microvascular angina and reperfusion-induced damage following coronary angioplasty. Kawai et al6 reported that the intravenous administration

Conclusion

CLEAN is a multicenter, randomized, double-blind, placebo-controlled trial comparing the intravenous administration of nicorandil and placebo as an adjunct to reperfusion therapy for acute STEMI. The trial is designed to provide a definitive report on the efficacy and safety of the intravenous infusion of nicorandil during PCI in patients with STEMI. The results of this trial will inform clinical practice and international guidelines.

Trial Status

Recruitment began in January 2021 and is estimated to complete in December 2023.

Funding

This study was supported by the National Key Research and Development Program of China (No. 2016YFC1301203), National Natural Science Foundation (No. 82170458) and Key Clinical Research Projects of National Clinical Research Center for Interventional Medicine (No. 2021-003).

Conflict of Interests

None reported.

Acknowledgments

The authors express their gratitude to all the clinical centers, hospitals and researchers participating in the CLEAN trial.

Cited by (0)

Dong Huang and Hongxian Wu contributed equally to this work.

View full text