臨床研究等提出・公開システム

A Single-blind, Randomized, Controlled, Parallel-group, Comparative Study Evaluating the Safety and Effectiveness of VER-01 as an Adjunct to Hemostasis During Cardiovascular Surgery

VER-01 Hemostasis in Cardiovascular Surgery Study

161

There were no significant discrepancies observed in the distribution of each item of subject demographic and baseline characteristics between the treatment groups. Overall, 86.9% (139/160 subjects) were male, and the mean age (SD) was 67.6 (10.4) years. All subjects were Japanese. There were no significant discrepancies in the distribution of surgical information between the treatment groups. Overall, the most common target disease was ischemic heart disease in 67.5% (36/160 patients), followed by aortic aneurysm in 27.5% (44/160 subjects). The most common surgical procedure was bypass surgery in 69.4% (111/160 patients), followed by vascular prosthesis surgery in 30.0% (48/160 subjects).

Of the 172 patients who consented to participate in the study, 161 patients were enrolled, and 11 patients were screen failures. All registered subjects were randomized (80 subjects in VER-01 group, 81 subjects in Beriplast P group), and 160 subjects (79 subjects in VER-01 group, 81 subjects in Beriplast P group) received investigational product. One subject in the VER-01 group could not receive investigational product due to device malfunction. A total of 151 subjects (73 subjects in VER-01 group, 78 subjects in Beriplast P group) completed the study. 161 randomized subjects (80 subjects in VER-01 group, 81 subjects in Beriplast P group) were included in the ITT. Of the 161 randomized subjects, 160 subjects (79 subjects in VER-01 group, 81 patients in Beriplast P group) were included in the SAF, excluding 1 subject in the VER-01 group who did not receive investigational product. mITT included 160 subjects (79 subjects in VER-01 group, 81 subjects in Beriplast P group), excluding 1 subject in the VER-01 group to whom investigational product of the randomized groups was not applied due to malfunction of the applicator device. A total of 152 subjects (75 subjects in VER-01 group, 77 subjects in Beriplast P group) were included in the PPS, excluding 8 subjects (4 subjects in VER-01 group, 4 subjects in Beriplast P group) with major protocol violations/deviations from the mITT set.

The incidence of adverse events in the SAF was 51.9% (41/79 subjects) in VER-01 group and 45.7% (37/81 subjects) in Beriplast P group. The incidence of serious adverse events was 15.2% (12/79 subjects) in VER-01 group and 13.6% (11/81 subjects) in Beriplast P group, and the incidence of severe adverse events was 7.6% (6/79 subjects) in VER-01 group and 6.2% (5/81 subjects) in Beriplast P group. Adverse events reported in >= 5% of subjects in VER-01 group were anaemia (11.4% [9/79 subjects]) and hepatic function abnormal (6.3% [5/79 subjects]). The adverse events reported in >= 5% of subjects in Beriplast P group was atrial fibrillation (6.2% [5/81]). The incidences of anaemia and hepatic function abnormal were >= 5% higher in VER-01 group than in Beriplast P group, however causal relationship to investigational product was ruled out. The incidence of adverse events related to investigational product was 1.3% (1/79 subjects) in VER-01 group and 1.2% (1/81 subjects) in Beriplast P group. The events included pericardial effusion (1 subject in VER-01 group) and haemorrhagic cerebral infarction (1 subject in Beriplast P group). Both were serious adverse events and the event of haemorrhagic cerebral infarction was also considered a severe adverse event. The incidence of procedure-related adverse events was 19.0% (15/79 subjects) in VER-01 group and 14.8% (12/81 subjects) in Beriplast P group. According to the reports by the study sites (investigator assessment), there were no AEs related to the concomitant medical device in either treatment group. However, hemorrhagic cerebral infarction reported in the Beriplast P group was considered to be related to the concomitant medical device in the opinion of the sponsor.

<Primary Endpoint>(Analysis set: mITT) - The success rate of hemostasis at 5 minutes following treatment application and with no re-bleeding requiring treatment at the target bleeding site (TBS) any time prior to initiation of final skin closure. (If the investigational product was reapplied later than 5 minutes after the application, the subject was treated as a hemostatic failure. ) 82.3% (65/79 subjects) (95% CI: 72.1~90.0) in VER-01 group and 85.2% (69/81 subjects) (95% CI: 75.6~92.1) in Beriplast P group The difference in the success rate for hemostasis between VER-01 group and Beriplast P group was - 2.9% (95% CI: - 14.7~8.9). The lower limit of the 95% CI of the difference was - 15.0% or higher, showing the non-inferiority of VER-01 group to Beriplast P group. <Secondary Endpoint>(Analysis set: mITT) - The success rate of hemostasis at 3, 7 and 10 minutes following treatment application and with no re-bleeding requiring treatment at the TBS any time prior to initiation of final skin closure. At 3 minutes after application, the success rate for hemostasis was 68.4% (54/79 subjects) (95% CI: 56.9~78.4) in VER-01 group and 77.8% (63/81 subjects) (95% CI: 67.2~86.3) in Beriplast P group at 3 minutes after application. The difference in the success rate for hemostasis between VER-01 group and Beriplast P group was - 9.4% (95% CI: - 23.1~4.2). At 7 minutes after application, the success rate for hemostasis was 87.3% (69/79 subjects) (95% CI: 78.0~93.8) in the VER-01 group and 86.4% (70/81 subjects) (95% CI: 77.0~93.0) in Beriplast P group, and the difference in the success rate for hemostasis between VER-01 group and Beriplast P group was 0.9% (95% CI: - 10.3~12.2). At 10 minutes after application, the success rate for hemostasis was 91.1% (72/79 subjects) (95% CI: 82.6~96.4) in VER-01 group and 91.4% (74/81 subjects) (95% CI: 83.0~96.5) in Beriplast P group, and the difference in the success rate for hemostasis between VER-01 group and Beriplast P group was - 0.2% (95% CI: - 10.3~9.9). - Subject rate of re-bleeding requiring treatment after initial establishment of TBS hemostasis at least 3 minutes after application. 5.3% (4/75 subjects) (95% CI: 1.5~13.1) in VER-01 group and 1.3% (1/75 subjects) (95% CI: 0.0~7.2) in Beriplast P group The difference in the proportion of subjects with rebleeding requiring intervention between the VER-01 group and Beriplast P group was 4.0% (95% CI: - 5.3~13.3).

This randomized controlled study demonstrated that VER-01 was non-inferior to Beriplast P when used as an adjunct to hemostasis for bleeding following vascular anastomosis in adult subjects undergoing elective surgical (excluding minimally invasive) revascularization procedures such as bypass surgery or artificial blood vessel replacement surgery of the coronary artery/aorta (including thoracic and abdominal regions)/peripheral artery or arteriovenous shunt creation.

Mar. 31, 2026

No

https://jrct.mhlw.go.jp/latest-detail/jRCT2031230363

Deura Imari

Johnson & Johnson K.K.

3-5-2, Nishi-Kanda, Chiyoda-ku, Tokyo, 101-0065, Japan

JJ_clinical@its.jnj.com

Dedicated contact

Johnson&Johnson K.K.

3-5-2, Nishi-Kanda, Chiyoda-ku, Tokyo, 101-0065, Japan

+81-3-4411-7200

JJ_clinical@its.jnj.com

Complete

Oct. 01, 2023

Interventional

randomized controlled trial

single blind

active control

parallel assignment

treatment purpose

Pre-operative
1.Subject undergoing elective, open, revascularization surgery such as bypass grafting and replacement of vascular prostheses for coronary artery, aorta (including thoracic and abdominal) and peripheral artery and arteriovenous shunt procedure.
2.At least 18 years of age at the time of informed consent.
3.Willingness to comply with the protocol.
4.Willingness to give consent before all study-related activities.

Intra-operative
1.Target bleeding site (mild and moderate bleeding) is identified, and requires adjunctive hemostasis determined by principal investigators and sub-investigators.

Pre-operative
1.Subjects with serious hepatic impairment (Either AST(GOT) or ALT(GPT) > 5 times the upper limit of site reference value).
2.Subjects suspected of having disseminated intravascular coagulation (DIC) (e.g., sepsis, acute leukemia, solid tumors).
3.Subjects who have intolerance to any of the components of the investigational or comparator products (including bovine-derived ingredients).
4.Subjects who are not willing to use blood products.
5.Subjects with immunodeficiency or undergoing treatment for immunodepression.
6.Subjects with hemolyzing property or blood loss anemia.
7.Subjects of childbearing potential with a positive pregnancy test or intent to become pregnant during the clinical study period.
8.Subjects who are breastfeeding.
9.Subjects who have participated in or will participate in another clinical trial of another a test drug/device within 30 days before and after a surgery of the clinical trial.
10.Subjects judged to be inappropriate by the principal investigator or sub-investigator.

Intra-operative
1.Subjects bleeding from only parenchyma tissue.
2.Subjects with an actively infected field of potential target bleeding site
3.Subjects who have serious complication in surgeries requiring emergency resuscitation or changing of planned surgeries.
4.Subjects judged to be inappropriate by the principal investigator or sub-investigators.

Both

Subject undergoing elective, open, revascularization surgery such as bypass grafting and replacement

Subjects, who are undergoing elective, open, revascularization surgery such as bypass grafting and replacement of vascular prostheses for coronary artery, aorta (including thorax and abdominal) and peripheral artery and arteriovenous shunt procedure, required an adjunctive hemostat on the anastomosis determined by principal investigators and sub-investigators are enrolled and randomized to VER-01 or Beriplast P in a 1:1 allocation ratio, and VER-01 or Beriplast P will be applied to the enrolled subjects.

The success rate of hemostasis at 5 minutes following treatment application and with no re-bleeding requiring treatment at the TBS any time prior to initiation of final chest wall closure.

+81-42-314-3111

July. 14, 2023

+81-6-6170-1070

July. 14, 2023

+81-93-511-2000

July. 14, 2023

+81-3-3353-8111

July. 14, 2023

+81-3-3964-9358

July. 14, 2023

none