Effects of Nicorandil on Microvascular Dysfunction in Patients With STEMI Undergoing Primary PCI

Official title

Evaluating the Effects of Nicorandil on Microvascular Dysfunction in Patients With ST-segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention

Overview

Despite the success of restoration of epicardial blood flow by the primary percutaneous coronary intervention (PPCI), approximately one half of patients with ST-segment elevation myocardial infarction (STEMI) have failed myocardial reperfusion, namely microvascular dysfunction. Previous studies have shown that coronary microvascular damage significantly impacts the prognosis of patients with STEMI. Therefore, restoration of microvascular function is quite important during the PPCI procedures. Recent clinical trials found that nicorandil, a hybrid ATP-sensitive potassium channel opening agent, improved microvascular function, prevented no-reflow phenomenon, and had beneficial cardioprotective effects in patients receiving PPCI. However, there was a lack of evidence on the protective effects of nicorandil on microvascular function. The coronary angiography-derived IMR (AMR) is a novel wire-free technology developed for fast computation of IMR in patients undergoing coronary angiography, thereby enabling the quantification of coronary microcirculation of patients. This study is aimed to investigate the effects of nicorandil on microvascular dysfunction as evaluated by AMR in patients with STEMI.

Detailed description

This study is aimed to investigate the effects of nicorandil on microvascular dysfunction as evaluated by AMR in patients with STEMI.

This study is a prospective, single-center, double-blind, randomized controlled study, evaluate the effects of nicorandil on nicorandil on microvascular dysfunction in patients with STEMI undergoing primary PCI.

The inclusion criteria are as following: Age between 18-80; Diagnosis of STEMI and indicating for primary PCI; Diagnostic coronary angiography showed definite culprit vessel and primary PCI was planned to treat the culprit vessel; Reference vessel diameter of culprit vessel was greater than 2.0 mm; There was no flow-limiting stenosis for the non-culprit vessels; Understand the aim of this trial and agree to sign the informed consent form.

The exclusion criteria are as following: Acute in- stent thrombosis or in-stent stenosis lesions of culprit vessel; Balloon angioplasty rather than stent was planned for the culprit vessel; Allergic to nicorandil or systolic arterial pressure was less than 85mmHg before procedure; Vessel with twisted shape that was unable to be measured using AMR; Oral or intravenous use of nicorandil within one month; Cardiac shock needing mechanical support; Severely hepatic dysfunction; Severely renal failure needing hemodialysis; Contraindicated for coronary angiography or primary PCI; Culprit vessels of left main or graft vessels; Pregnant or nursing; Others that investigators think should excluded.

Patients were randomized into nicorandil group and control group with ratio of 1:1. In the nicorandil group, intracoronary nicorandil 3mg dissolved in 3ml saline was given within 30 seconds at two time points, one was when the guidewire or ballon passed the lesion and the blood flow was regained, and another was the time before the stent was implanted. In the control group, 3ml saline was given intracoronary through the guiding catheter within 30 seconds at the same time points in nicorandil group. All the procedure details including strategies, decision of intravascular imaging, other medications during procedures were decided by operators.

The angiography-derived microcirculatory resistance (AMR) is a wire-free and adenosine-free index, which aims at providing a valid alternative to invasive wire-based IMR assessment.

Interventions

• Drug nicorandil
  In the nicorandil group, intracoronary nicorandil 3mg dissolved in 3ml saline was given within 30 seconds at two time points, one was when the guidewire or ballon passed the lesion and the blood flow was regained, and another was the time before the stent was implanted.
• Drug Saline (NaCl 0,9 %) (placebo)
  In the control group, 3ml saline was given intracoronary through the guiding catheter within 30 seconds at the same time points in nicorandil group.

Primary outcome measures

• The value of post-PCI AMR [Time frame: The time immediate after primary PCI]

Secondary outcome measures (4)

• Prevalence of slow flow or no-flow during procedure [Time frame: During primary PCI procedure]
• ST-segment resolution two hours after primary PCI [Time frame: Two hours after primary PCI]
• In-hospital peak troponin level [Time frame: From the enrollment to 7 days after primary PCI]
• Prevalence of hypotension during procedure [Time frame: During primary PCI procedure]

Eligibility criteria

Inclusion criteria

• Age between 18-80
• Diagnosis of STEMI and indicating for primary PCI
• Diagnostic coronary angiography showed definite culprit vessel and primary PCI was planned to treat the culprit vessel.
• Reference vessel diameter of culprit vessel was greater than 2.0 mm
• There was no flow-limiting stenosis for the non-culprit vessels.
• Understand the aim of this trial and agree to sign the informed consent form.

Exclusion criteria

• Acute in- stent thrombosis or in-stent stenosis lesions of culprit vessel.
• Balloon angioplasty rather than stent was planned for the culprit vessel.
• Allergic to nicorandil or systolic arterial pressure was less than 85mmHg before procedure
• Vessel with twisted shape that was unable to be measured using AMR
• Oral or intravenous use of nicorandil within one month.
• Cardiac shock needing mechanical support.
• Severely hepatic dysfunction.
• Severely renal failure needing hemodialysis.
• Contraindicated for coronary angiography or primary PCI.
• Culprit vessels of left main or graft vessels.
• Pregnant or nursing.
• Others that investigators think should excluded.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Publications

• Wang X, Guo Q, Guo R, Guo Y, Yan Y, Gong W, Zheng W, Wang H, Ai H, Que B, Xu L, Huo Y, Fearon WF, Nie S. Coronary angiography-derived index of microcirculatory resistance and evolution of infarct pathology after ST-segment-elevation myocardial infarction. Eur Heart J Cardiovasc Imaging. 2023 Nov 23;24(12):1640-1652. doi: 10.1093/ehjci/jead141. PMID 37319341
• Hirohata A, Yamamoto K, Hirose E, Kobayashi Y, Takafuji H, Sano F, Matsumoto K, Ohara M, Yoshioka R, Takinami H, Ohe T. Nicorandil prevents microvascular dysfunction resulting from PCI in patients with stable angina pectoris: a randomised study. EuroIntervention. 2014 Jan 22;9(9):1050-6. doi: 10.4244/EIJV9I9A178. PMID 24457276
• Qian G, Zhang Y, Dong W, Jiang ZC, Li T, Cheng LQ, Zou YT, Jiang XS, Zhou H, A X, Li P, Chen ML, Su X, Tian JW, Shi B, Li ZZ, Wu YQ, Li YJ, Chen YD. Effects of Nicorandil Administration on Infarct Size in Patients With ST-Segment-Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention: The CHANGE Trial. J Am Heart Assoc. 2022 Sep 20;11(18):e026232. doi: 10.1161/JAHA.1 PMID 36073634

Identifiers

NCT: NCT06787430 · 2024-2375

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗