UMIN-CTR Clinical Trial

Unique ID issued by UMIN UMIN000022652
Receipt number R000026114
Scientific Title Impact of Apixaban on clinical outcome of the patients with Large Vessel Occlusion or stenosis
Date of disclosure of the study information 2016/06/08
Last modified on 2021/06/17 11:02:01

* This page includes information on clinical trials registered in UMIN clinical trial registed system.
* We don't aim to advertise certain products or treatments


Basic information

Public title

Impact of Apixaban on clinical outcome of the patients with Large Vessel Occlusion or stenosis

Acronym

ALVO trial

Scientific Title

Impact of Apixaban on clinical outcome of the patients with Large Vessel Occlusion or stenosis

Scientific Title:Acronym

ALVO trial

Region

Japan


Condition

Condition

Acute ischemic stroke

Classification by specialty

Neurosurgery

Classification by malignancy

Others

Genomic information

NO


Objectives

Narrative objectives1

The aim of this study is to investigate the clinical events of the patients with acute cerebral large vessel occlusion or stenosis and atrial fibrillation, treated by apixaban within 14 days after onset. This is the observational study that patients will be made the registration at the timing of both retrospective period and prospective period.

Basic objectives2

Safety,Efficacy

Basic objectives -Others


Trial characteristics_1


Trial characteristics_2


Developmental phase



Assessment

Primary outcomes

Death and ischemic/bleeding events within 90 days after disease onset

Key secondary outcomes




Base

Study type

Observational


Study design

Basic design


Randomization


Randomization unit


Blinding


Control


Stratification


Dynamic allocation


Institution consideration


Blocking


Concealment



Intervention

No. of arms


Purpose of intervention


Type of intervention


Interventions/Control_1


Interventions/Control_2


Interventions/Control_3


Interventions/Control_4


Interventions/Control_5


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


Not applicable

Gender

Male and Female

Key inclusion criteria

1. Patients 20 years and older with acute stroke and treated with oral apixaban within 14 days after onset.
2. Patients who are hospitalized in a period from Oct 1, 2014 to Feb 28, 2018
3. Patients with acute cerebral large vessel occlusion or stenosis (> 50%)
4. Patients with non-valvular atrial fibrillation
5. Patients who are not confirmed ICH by MRI or CT within 24 hours after r-tPA infusion.

Key exclusion criteria

1. Patients who are considered to be ineligible for the study participation by the investigator.
2. Patients who are pregnant or potentially pregnant.
3. Patients who have a history of hypersensitivity to apixaban
4. Patients with hepatic disease having coagulation disorder and clinically important bleeding risk
5. Patients with renal failure (creatinine clearance<15 mL/min)
6. Patients with Active pathological bleeding including intracranial bleeding of any type

Target sample size

700


Research contact person

Name of lead principal investigator

1st name
Middle name
Last name Shinichi Yoshimura

Organization

Hyogo College of Medicine

Division name

Department of Neurosurgery

Zip code


Address

1-1 Mukogawa, Nishinomiya, Hyogo 663-8501

TEL

+81-798-45-6455

Email

alvo@hyo-med.ac.jp


Public contact

Name of contact person

1st name
Middle name
Last name Kazutaka Uchida

Organization

Hyogo College of Medicine

Division name

Department of Neurosurgery

Zip code


Address

1-1 Mukogawa, Nishinomiya, Hyogo 663-8501

TEL

+81-798-45-6455

Homepage URL


Email

alvo@hyo-med.ac.jp


Sponsor or person

Institute

Hyogo college of medicine

Institute

Department

Personal name



Funding Source

Organization

Hyogo College of Medicine
Bristol-Myers Squibb

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


Address


Tel


Email



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



Other administrative information

Date of disclosure of the study information

2016 Year 06 Month 08 Day


Related information

URL releasing protocol

http://www.clinicaltrials.gov. NCT02818868

Publication of results

Published


Result

URL related to results and publications

http://www.clinicaltrials.gov. NCT02818868

Number of participants that the trial has enrolled

713

Results

The cumulative incidence of primary outcome was similar between the two groups. The crude HR of the Early group was 1.19 and the adjusted HR was 1.32 within 365 days.

Results date posted

2021 Year 06 Month 17 Day

Results Delayed


Results Delay Reason


Date of the first journal publication of results


Baseline Characteristics

The inclusion criteria were patients aged at least 20 years, with acute ischemic stroke with LVO or intra-/ extra-cranial artery stenosis and NVAF, and received apixaban within 14 days after the onset. To reflect the real- world clinical practice of LVO, we included peripheral artery occlusions such as M2-3, A1-2, or P1-2. We also included acute ischemic stroke with intra-/extra-cranial artery stenosis defined as over 50%, because anticoagulants were considered effective in patients with concomitant atherosclerotic diseases and NVAF [11, 12]. On the contrary, the exclusion criteria were patients who are considered ineligible for the study by the investigator, pregnant or potentially pregnant, have a his- tory of hypersensitivity to apixaban, with hepatic disease hav- ing coagulation disorder and clinically important bleeding risk, with renal failure (creatinine clearance < 15 mL/min), and with pathological bleeding including intracranial bleeding of any type. The diagnostic and treatment modalities were determined by the physician-in-charge including rt-PA and EVT. The rt-PA used was alteplase, which was administered intravenously at 0.6 mg/kg [13], and EVT consisted of any type of intravascular therapy including thrombectomy using any device approved in Japan.

Participant flow

We initially registered 713 patients, and 27 patients were ex- cluded due to ineligibility, duplicate registration, and refusal to provide informed consent. The median time from onset to apixaban administration was 2.5 days . There were 263 and 423 patients in the Early and Late groups, respectively. The mean age (SD) of enrolled patients was 77.5 (9.7) years, and men accounted for 52 of the patients. Overall, 138 (20.1) and 160 (23.3) patients received antiplatelet and anticoagulant drugs before the onset, respectively. The rt-PA and EVT were conducted in 268 (39.1) and 358 (52.2) patients, respectively. Two-thirds of the patients had no dis- ability (mRS 0) before onset.

Adverse events

Ischemic events before apixaban administration occurred in three cases, which were all cerebral infarctions in the Late group. Their ASPECTS on admission were 2, 7, and 8 points. In addition, all ischemic events occurred on the 3rd day after the onset.
We tabulated the details of ISTH major bleeding events within 30 days after apixaban administration (Supplemental Table III). Eight of nine patients in the Early group and 7 of 12 patients in the Late group received rt-PA or EVT. The background of patients who developed bleeding events in 30 days was generally similar between the groups.

Outcome measures

The primary outcome of this analysis was a composite of all- cause death, International Society on Thrombosis and Haemostasis (ISTH) major bleeding events, [21], and ische- mic events. Ischemic events included ischemic stroke, acute coronary syndrome, acute myocardial infarction, or systemic embolism after apixaban administration. The secondary out- comes were each component of the primary outcome. Additionally, we assessed intracranial hemorrhage and ische- mic stroke separately due to a safety concern. We analyzed these outcomes at 30, 90, and 365 days after the onset.

Plan to share IPD


IPD sharing Plan description



Progress

Recruitment status

Completed

Date of protocol fixation

2016 Year 05 Month 02 Day

Date of IRB

2016 Year 03 Month 10 Day

Anticipated trial start date

2016 Year 06 Month 01 Day

Last follow-up date

2019 Year 05 Month 31 Day

Date of closure to data entry


Date trial data considered complete


Date analysis concluded



Other

Other related information

observational study


Management information

Registered date

2016 Year 06 Month 08 Day

Last modified on

2021 Year 06 Month 17 Day



Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000026114


Research Plan
Registered date File name
2021/06/17 ALVO_Protoco_Ver2.3.docx

Research case data specifications
Registered date File name
2021/06/17 Yoshimura_et_al-2020-Translational_Stroke_Research.pdf

Research case data
Registered date File name
2021/06/17 Yoshimura_et_al-2020-Translational_Stroke_Research.pdf