UMIN-CTR Clinical Trial

Basic information
Public title	A prospective randomized clinical trial, the effect of long acting CCBs in post-acute myocardial infarction patients
Acronym	ACROSS-AMI (ACh-induced Coronary Spasm Study - Nifedipine and Benidipine After Acute Myocardial Infarction)
Scientific Title	A prospective randomized clinical trial, the effect of long acting CCBs in post-acute myocardial infarction patients
Scientific Title:Acronym	ACROSS-AMI (ACh-induced Coronary Spasm Study - Nifedipine and Benidipine After Acute Myocardial Infarction)
Region	Japan

Condition
Condition	ST-segment elevation myocardial infarction(STEMI) or non-ST elevation myocardial infarction(NSTEMI)
Classification by specialty	Medicine in general Cardiology
Classification by malignancy	Others
Genomic information	NO

Objectives
Narrative objectives1	To investigate the inhibitory effect of CCBs (Nifedipine / Adalat CR or Benidipine / Coniel) on coronary spasm and coronary endothelial dysfunction.
Basic objectives2	Safety,Efficacy
Basic objectives -Others
Trial characteristics_1	Exploratory
Trial characteristics_2	Pragmatic
Developmental phase	Phase IV

Assessment
Primary outcomes	A rate of changes in ACh-provoked coronary constrictive response and degree of coronary vascular tone at the follow up CAG, 6-12 months after onset.
Key secondary outcomes	(1)Incidence of coronary spasm at the 2nd ACh-provocation test (2)Change in biomarkers (3)Cardiovascular events(cardiovascular death, non-fatal MI, UAP, rehospitalization for heart failure, re-PCI etc) (4)Adverse effects (5)Coronary lesion finding by OCT(if possible)

Base
Study type	Interventional

Study design
Basic design	Parallel
Randomization	Randomized
Randomization unit	Individual
Blinding	Open -no one is blinded
Control	Active
Stratification	YES
Dynamic allocation	YES
Institution consideration	Institution is considered as a block.
Blocking	YES
Concealment	Central registration

Intervention
No. of arms	5
Purpose of intervention	Treatment
Type of intervention	Medicine
Interventions/Control_1	ACh-provocation test positive / Nifedipine arm
Interventions/Control_2	ACh-provocation test positive / Benidipine arm
Interventions/Control_3	ACh-provocation test negative / Control arm
Interventions/Control_4	ACh-provocation test negative / Nifedipine arm
Interventions/Control_5	ACh-provocation test negative / Benidipine arm
Interventions/Control_6
Interventions/Control_7
Interventions/Control_8
Interventions/Control_9
Interventions/Control_10

Eligibility
Age-lower limit	20 years-old <=
Age-upper limit	85 years-old >
Gender	Male and Female
Key inclusion criteria	1) Patients that ACh-provocation test was performed within 2 weeks after hospitalization and no PCI-needed residual lesions were observed at discharge 2) Age: 20-85 years old 3) Patients that written informed consents were obtained
Key exclusion criteria	Patients with 1) Unstable angina (UAP) 2) Triple vessel disease 3) Left ventricular ejection fraction <40% 4) Chronic atrial fibrillation 5) Severe hepatic dysfunction 6) Low tolerability of DHP-CCB 7) A history of DES implantation 8) Patients who were recognized by the chief physician to be inappropriate for study participation
Target sample size	160

Research contact person
Name of lead principal investigator	1st name Hisao Middle name Last name Ogawa
Organization	Graduate School of Medical Sciences, Kumamoto University
Division name	Department of Cardiovascular Medicine
Zip code	860-8556
Address	1-1-1, Honjo, Chuo-ku, Kumamoto
TEL	096-373-5175
Email	ogawah@kumamoto-u.ac.jp

Public contact
Name of contact person	1st name Koichi Middle name Last name Kaikita
Organization	Graduate School of Medical Sciences, Kumamoto University
Division name	Department of Cardiovascular Medicine
Zip code	860-8556
Address	1-1-1, Honjo, Chuo-ku, Kumamoto
TEL	096-373-5175
Homepage URL
Email	kaikitak@kumamoto-u.ac.jp

Sponsor
Institute	Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University
Institute
Department

Funding Source
Organization	Bayer Yakuhin Ltd.
Organization
Division
Category of Funding Organization	Profit organization
Nationality of Funding Organization

Other related organizations
Co-sponsor
Name of secondary funder(s)

IRB Contact (For public release)
Organization	Institutional Review Board
Address	1-1-1, Honjo, Chuo-ku, Kumamoto
Tel	096-373-5657
Email	iyg-igaku@jimu.kumamoto-u.ac.jp

Secondary IDs
Secondary IDs	NO
Study ID_1
Org. issuing International ID_1
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions
Institutions	熊本大学医学部附属病院(熊本県) 済生会熊本病院(熊本県) 横浜市立大学市民総合医療センター(神奈川県) 愛媛県立新居浜病院(愛媛県) 国立循環器病研究センター(大阪府) 日本医科大学千葉北総病院(千葉県) 昭和大学藤が丘病院(神奈川県) 広島鉄道病院(広島県) 東京女子医大八千代医療センター(千葉県) 心臓血管研究所付属病院(東京都)

Other administrative information
Date of disclosure of the study information	2013 Year 02 Month 21 Day

Related information
URL releasing protocol	None
Publication of results	Unpublished

Result
URL related to results and publications	None
Number of participants that the trial has enrolled	97
Results	There were no significant differences in the baseline clinical characteristics except younger age in nifedipine compared with benidipine groups. In age-adjusted model, the difference of dilator response to ISDN between initial and follow-up ACh tests was almost identical between 2 groups. However, the difference of constrictor response to ACh was significantly improved in the nifedipine rather than benidipine groups.
Results date posted	2022 Year 09 Month 24 Day
Results Delayed
Results Delay Reason
Date of the first journal publication of results
Baseline Characteristics	There were no significant differences in baseline clinical characteristics except younger age in nifedipine compared with benidipine groups.
Participant flow	ACROSS-AMI study is an open label, multicenter study of 97 consecutive AMI patients who underwent percutaneous coronary intervention (PCI) and had no residual stenosis in major left coronary artery (LCA). The 84 AMI patients who were positive for initial acetylcholine (ACh) provocation test in LCA (LACh) 1-2 weeks post-MI were randomized into 2 groups treated with nifedipine (N=43) and benidipine (N=41). After exclusion of 14 patients, data of 70 AMI patients [nifedipine (N=35) and benidipine (N=35)] were eligible for the present analysis.
Adverse events	In studies 1 and 2, the nifedipine group (studies 1 + 2: 48 subjects) had hypotension (1 patient, 2.1%), headache (1 patient, 2.1%), edema (1 patient, 2.1%), A dull headache (1 patient, 2.1%) was observed, and an adverse event of skin eruption (1 patient, 2.3%) was observed in the benidipine group (Study 1: 43 patient).
Outcome measures	The primary end point is the changes in coronary vasodilator response to ISDN and vasoconstrictor response to ACh by using QCA between ACh provocation test 2 weeks and 6-9 months after AMI. Coronary vasodilator response to ISDN and Coronary vasoconstrictor response to ACh were calculated by the following formula.
Plan to share IPD
IPD sharing Plan description

Progress
Recruitment status	Completed
Date of protocol fixation	2013 Year 01 Month 16 Day
Date of IRB	2013 Year 12 Month 03 Day
Anticipated trial start date	2013 Year 08 Month 07 Day
Last follow-up date	2017 Year 05 Month 31 Day
Date of closure to data entry
Date trial data considered complete
Date analysis concluded

Other
Other related information

Management information
Registered date	2013 Year 02 Month 21 Day
Last modified on	2022 Year 09 Month 24 Day

Link to view the page
URL(English)	https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000011818