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PCSK9 Inhibitor Usage on Target Vessel Dysfunction in patients with hypercholesterolemia after coronary stenting, a Multicenter Randomized Controlled Trial
(CuVIC-2 Trial)

PCSK9 Inhibitor Usage on Target Vessel Dysfunction in patients with hypercholesterolemia after coronary stenting, a Multicenter Randomized Controlled Trial (CuVIC-2 Trial)

44

The number of informed consents obtained was 44, 23 were assigned to the evolocumab + statin combination group (EV+S group), and 18 were assigned to the statin treatment group (S group). EV+S group: male 19 (82.6 %), female 4 (17.4 %), age (mean +- SD) 62.3 +- 13.3 years. S group: male 13 (72.2 %), female 5 (27.8 %), age (mean +- SD) 63.8 +- 10.6 years. Of these, 1 patient in the S group did not meet the registration criteria, and 1 patient in the EV+S group who never received study treatment at all after the assignment. 39 patients with FAS (EV+S group 22, S group 17).

This study initiated patient selection following the Kyushu University CRB approval date of September 8, 2020, the notification date to the Kyushu Health Bureau on September 25, 2020, and the jRCT publication date on September 29, 2020. The registration began with the first patient allocation at Kyushu University Hospital on November 26, 2020. The research plan originally aimed to register 160 cases. However, due to the impact of the COVID-19 pandemic on participating research facilities, only 40 cases were registered by September 2022. As a result, the research plan was modified (CRB approval: November 25, 2022), adjusting the target number of cases to 42. The primary endpoint was shifted to the original secondary endpoint, while maintaining the exploratory trial design. The registration concluded on September 30, 2022. Of the 44 individuals who gave their consent were registered, and 41 were randomized: 23 in the Evolocumab plus statin combination group (hereafter, EV+S group) and 18 in the statin treatment group (hereafter, S group). Among these, one case in the S group did not meet the registration criteria, and one case in the EV+S group never received the investigational drug. Thus, the FAS (Full Analysis Set) consisted of 39 cases (EV+S group: 22, S group: 17). The trial for all registered patients was concluded on March 14, 2023. The primary endpoint, coronary angiography and measurement of coronary constriction to acetylcholine, was possible for 19 individuals in the EV+S group and 15 in the S group.

A total of 8 adverse events occurred in both groups (7 in the EV+S group and 1 in the S group), including 5 serious adverse events in the EV+S group. EV+S group - Serious adverse events: Septic shock (1 patient), Colorectal adenoma (1 patient), Vasospastic angina (1 patient), Cardiac ventricular thrombosis (1 patient), Cardiac procedure complication (1 patient) - Adverse events: Myalgia (1 patient), Blood creatine phosphokinase increased (1 patient) S group - Serious adverse events: none - Adverse events: Blood creatine phosphokinase increased (1 patient)

Primary Endpoint The primary endpoint, coronary contractions to low, medium or high-dose intracoronary acetylcholine, were measured in 19 subjects in EV+S group and 15 subjects in the S group. Coronary contraction to acetylcholine was not different between 2 groups; the mean difference was 4.8% (95% CI: -13.6% to 23.2%), p=0.5953 by mixed model for repeated measures (MMRM). Secondary Endpoints - For LDL-C, both in terms of measured values and the rate of change from baseline, the EV+S group showed a significantly greater decrease than the S group. The difference at day 197 was -59.8mg/dL (p<0.0001), with a change rate of -69.04% (p<0.0001). - Regarding the achievement rate of the LDL-C management target of less than 70mg/dL, the EV +S group was 100%, while the S group was 5.9%, showing a significant difference (p<0.0001). - For the incidence rate of Coronary Endothelial Dysfunction (CED), the EV+S group 73.7(51.2 - 88.2) % vs. the S group 66.7(41.7 - 84.8) %; there was no statistically significant difference (p = 0.6561). - For the Target Vessel Dysfunction (TVD), the EV+S group 73.7 (51.2 - 88.2) % vs. the S group 68.8 (44.4 - 85.8) %; there was no statistically significant difference (p=0.6937).

In high-risk coronary artery disease patients after the successful placement of a coronary stent who did not achieve LDL-C <70 mg/dL under high-dose statin administration (with or without concomitant use of ezetimibe), the administration of evolocumab through randomization significantly reduced LDL-C; however, no improvement was observed in the coronary endothelial function.

June. 30, 2024

No

Not applicable

https://jrct.mhlw.go.jp/latest-detail/jRCTs071200032

Matoba Tetsuya

Kyushu University Hospital

3-1-1, Maidashi, Higashi-ku, Fukuoka

matoba@cardiol.med.kyushu-u.ac.jp

Matoba Tetsuya

Kyushu University Faculty of Medical Sciences

3-1-1, Maidashi, Higashi-ku, Fukuoka

+81-92-642-5360

matoba@cardiol.med.kyushu-u.ac.jp

Complete

Sept. 29, 2020

Interventional

randomized controlled trial

open(masking not used)

active control

parallel assignment

treatment purpose

Coronary artery disease patients who underwent successful coronary stenting and will receive investigating lipid-lowering therapy within 8 weeks.
Patients whose LDL-C goal is <70mg/dL according to the Japanese Atherosclerosis Sciety Guideline 2022.
Patients who have LDL-C Cholesterol equal or more than 70 mg/dL and less than 140mg/dL (Friedewad's formula) under the treatment with high-dose or maximum tolerated dose of statins) with or without ezetimibe.

Patients who are planned coronary revascularization procedure(s) for residual coronary artery lesion(s).
Patients who have undergone a coronary artery bypass grafting.
Patients who have severe left ventricular dysfunction (LVEF<30% by ultrasound).

Both

Hypercholesterolemia after coronary stenting

statins given on day1 every day in orally and Evolocumab 140mg every 2weeks by hypodermic injection
statins given on day1 every day in orally

hypercholesterolemia

Severity of coronary vasoconstriction (percent change of coronary vessel diameter) induced by the intracoronary Ach in the stent target vessel at 197 days (28 weeks) after the first administration of test drug.

(1) Serum LDL cholesterol at 197 days (28 weeks) after administration of test drugs.
(2) Percent change in serum LDL cholesterol from baseline at 197 days (28 weeks) after administration of test drugs.
(3) The proportion of the subjects who achieved LDL-C goal as recommended by the JAS guideline (LDL-C <70 mg/dL) at 197 days (28 weeks) after administration of test drug.
(4) The incidence of coronary endothelial dysfunction (CED) in the stent target vessel at 197 days (28 weeks) after the first administration of test drug
(5) The incidence of target vessel dysfunction (TVD), which is a composite of CED, TVR, MI, and target vessel-related death at 197 days (28 weeks) after the first administration of test drug.

+81-92-642-5082

Sept. 08, 2020

none