UMIN-CTR Clinical Trial

Public title

Early and Short-term Use of PCSK9-Inhibitors on Coronary Plaque Stability in Acute Coronary Syndrome

Acronym

Adage-Joto study

Scientific Title

Early and Short-term Use of PCSK9-Inhibitors on Coronary Plaque Stability in Acute Coronary Syndrome

Scientific Title:Acronym

Adage-Joto study

Region

Japan

Condition

The acute coronary syndrome patients with dyslipidemia who undewent percutanous coronary intervention.

Classification by specialty

Cardiology

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

Assessment of acute efficacy of short-term of PCSK9 antibody usage on coronary plaque stability in acute coronary syndrome patients by optical coherence tomography analysis

Basic objectives2

Efficacy

Basic objectives -Others

Trial characteristics_1

Exploratory

Trial characteristics_2

Pragmatic

Developmental phase

Phase IV

Primary outcomes

Change of fibrous cap thickness at 9 month follow-up OCT

Key secondary outcomes

Secondary endpoints included changes in the MFCT from baseline to the 3-month follow-up, percentage change in the MFCT and lipid arc in the region of interests from baseline to the 3- and 9-month follow-ups.

Study type

Interventional

Basic design

Parallel

Randomization

Randomized

Randomization unit

Individual

Blinding

Open -no one is blinded

Control

Active

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

No. of arms

2

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

PCSK9 inhibitors
per-month for 3months
+atrvastatin 20mg/day

Interventions/Control_2

atrvastatin 20mg/day

Interventions/Control_3

Interventions/Control_4

Interventions/Control_5

Interventions/Control_6

Interventions/Control_7

Interventions/Control_8

Interventions/Control_9

Interventions/Control_10

Age-lower limit

20

years-old

<=

Age-upper limit

85

years-old

>=

Gender

Male and Female

Key inclusion criteria

1)The age is more than 20 years old
2)acute coronary syndrome patients
3)medical history of dyslipidemia
4)LDL-C>70mg after atrvastatin(20mg)treatment
5) to get initial success of Percutanous cotonary intervension(PCI)
6)Existence of fibrous cap with lipid-rich plaque in the non-culprit lesion
7) capable of follow-up OCT at baseline,3month and 9month follow-up

Key exclusion criteria

1) The patients previously used PCSK9 antibody
2)the patient with Hemodialysis and renal insufficiency
3)severe heart failure(NYHA>3)
4)contraindication and intolerance for statin
5)contraindication for PCSK9 antibody
6)Use of other lipid-lowering therapy(ezetimib,DHA,EPA)

Target sample size

80

Name of lead principal investigator

1st name	Hiroki
Middle name
Last name	Uehara

Organization

Urasoe general hospital

Division name

Cardiovascular center

Zip code

9012132

Address

4-16-1,Urasoe city,Okinawa

TEL

098-878-0231

Email

cardioexpham1225@hotmail.com

Name of contact person

1st name	Hiroki
Middle name
Last name	Uehara

Organization

Urasoe general hospital

Division name

cardiovascular center

Zip code

9012132

Address

4-16-1,Urasoe city,Okinawa

TEL

098-878-0231

Homepage URL

Email

cardioexpham1225@hotmail.com

Institute

Urasoe general hospital

Institute

Department

Personal name

Hiroki Uehara

Organization

Urasoe general hospital

Organization

Division

Category of Funding Organization

Other

Nationality of Funding Organization

none

Co-sponsor

Name of secondary funder(s)

Organization

Urasoe general hospiral Insitute review board

Address

4-16-1,Iso Urasoe city,Okinawa

Tel

098-878-0231

Email

kenkyu@jin-aikai.xsrv.jp

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

Date of disclosure of the study information

2017

Year

03

Month

13

Day

URL releasing protocol

https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000030449

Publication of results

Unpublished

URL related to results and publications

https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000030449

Number of participants that the trial has enrolled

52

Results

Change in LDL-C levels from baseline to 3 months were significantly greater in the PCSK9I group(-75.1% vs -14.1% ; p=0.006). Change in MFCT from baseline to 9 months were significantly greater in the PCSK9I group, despite a re-elevation in LDL-C levels after PCSK9 inhibitor discontinuation(100micrometer;IQR:45-175maicrometere vs 50micrometer;IQR:10-110micrometer;p=0.032).

Results date posted

2023

Year

06

Month

24

Day

Results Delayed

Delay expected

Results Delay Reason

Data collection took time due to the COVID19 disaster.

Date of the first journal publication of results

Baseline Characteristics

Patients with STEMI-ACS who had undergone successful PCI for the culprit lesion, had intermediate, non-culprit lesions suitable for OCT examination, and had LDL cholesterol levels of more than 100 mg/dL at hospital admission and more than 70 mg/dL even after receiving the maximum tolerated dose of atorvastatin (20 mg/day) as per Japanese local guidelines for 7 days prior to randomization were eligible for the study. The target lesion had a diameter stenosis percentage of between 30% and 70%, as estimated by visual assessment on angiography. The target lesion could be situated in either a coronary artery that had undergone PCI or one that had not; however, if it was in a PCI-treated coronary artery, it had to be more than 10 mm away from the PCI-treated lesion. The exclusion criteria included cardiogenic shock, the need for coronary artery bypass grafting, renal insufficiency (eGFR <30 mL/min/1.73 m^2), malignancy, statin intolerance, prior or current use of PCSK9 inhibitors, and active systemic inflammation.

Participant flow

The study population consisted of 62 patients.Participants were randomized in a 1:1 ratio to receive PCSK9Is therapy or to serve as controls. Of these, 8 individuals who did not undergo serial OCT examination at baseline, 3 months, and 9 months were excluded. Ultimately, 52 patients underwent serial OCT examination in accordance with the protocol, with 29 in the PCSK9i group and 23 in the control group.

Adverse events

There was one case of target lesion revascularization after the start of the trial in either group (1(3.4%) in PCSK9I group vs. 1(4.3%) in the SoC group). However, there was no cardiac death, target-lesion-related myocardial infarction or adverse drug reactions in either group.

Outcome measures

The primary endpoint of the study was the change in minimum fibrous cap thickness from baseline to the 9-month follow-up, with secondary endpoints including changes in minimum fibrous cap thickness from baseline to the 3-month follow-up, percentage change in minimum fibrous cap thickness, and lipid arc in the region of interests from baseline to 3 and 9 months.

Plan to share IPD

The data underlying this article will be shared on reasonable request to the corresponding author.

IPD sharing Plan description

Recruitment status

No longer recruiting

Date of protocol fixation

2017

Year

03

Month

07

Day

Date of IRB

2017

Year

03

Month

07

Day

Anticipated trial start date

2017

Year

03

Month

13

Day

Last follow-up date

2020

Year

03

Month

31

Day

Date of closure to data entry

2020

Year

11

Month

01

Day

Date trial data considered complete

2020

Year

11

Month

01

Day

Date analysis concluded

2023

Year

05

Month

01

Day

Other related information

Registered date

2017

Year

03

Month

13

Day

Last modified on

2023

Year

12

Month

05

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000030449