UMIN-CTR Clinical Trial

Unique ID issued by UMIN UMIN000011630
Receipt number R000011778
Scientific Title THrombolysis for Acute Wake-up and unclear-onset Strokes with alteplase at 0.6 mg/kg (THAWS) Trial
Date of disclosure of the study information 2013/09/09
Last modified on 2020/12/15 10:43:19

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Basic information

Public title

THrombolysis for Acute Wake-up and unclear-onset Strokes
with alteplase at 0.6 mg/kg (THAWS) Trial

Acronym

THAWS Trial

Scientific Title

THrombolysis for Acute Wake-up and unclear-onset Strokes
with alteplase at 0.6 mg/kg (THAWS) Trial

Scientific Title:Acronym

THAWS Trial

Region

Japan


Condition

Condition

acute ischemic stroke

Classification by specialty

Neurology Radiology Neurosurgery
Emergency medicine

Classification by malignancy

Others

Genomic information

NO


Objectives

Narrative objectives1

To clarify efficacy and safety of intravenous thrombolysis for patients with acute wake-up ischemic stroke and those having acute ischemic stroke with unknown time of stroke onset

Basic objectives2

Safety,Efficacy

Basic objectives -Others


Trial characteristics_1


Trial characteristics_2


Developmental phase



Assessment

Primary outcomes

modified Rankin Scale 0-1 at 90 days

Key secondary outcomes

A prespecified ordinal analysis of the modified Rankin score at 90 days,
symptomatic intracranial hemorrhage within 24 h,
Infarct volume at 7 days,
Infarct volume growth at 7 days,
etc


Base

Study type

Interventional


Study design

Basic design

Parallel

Randomization

Randomized

Randomization unit

Individual

Blinding

Open -but assessor(s) are blinded

Control

Active

Stratification


Dynamic allocation


Institution consideration


Blocking


Concealment



Intervention

No. of arms

2

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

Intervention: intravenous rt-PA

Interventions/Control_2

Control: standard medical therapy including antithrombotics

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

Clinical diagnosis of acute ischemic stroke with unknown time of symptom onset
Last known well without neurological symptoms >4.5 h of treatment initiation
Treatment can be initiated <4.5 h of symptom recognition
ASPECTS on DWI >5
No marked parenchymal hyperintensity on FLAIR
Baseline NIHSS >=2

Key exclusion criteria

Prestroke mRS >1
Ineligible for IV rt-PA according to the Japanese guideline (J Stroke Cerebrovasc Dis. 2013 Jul;22:571-600)
Contraindication to MRI, etc

Target sample size

300


Research contact person

Name of lead principal investigator

1st name Masatoshi
Middle name
Last name Koga

Organization

National Cerebral and Cardiovascular Center

Division name

Department of Cerebrovascular Medicine

Zip code

565-8565

Address

5-7-1 Fujishirodai, Suita, Osaka 565-8565, JAPA

TEL

06-6833-5012

Email

toyoda@ncvc.go.jp


Public contact

Name of contact person

1st name Masatoshi
Middle name
Last name Koga

Organization

National Cerebral and Cardiovascular Center

Division name

Department of Cerebrovascular Medicine

Zip code

565-8565

Address

5-7-1 Fujishirodai, Suita, Osaka 565-8565, JAPA

TEL

06-6833-5012

Homepage URL

http://thaws.stroke-ncvc.jp/

Email

koga@ncvc.go.jp


Sponsor or person

Institute

National Cerebral and Cardiovascular Center

Institute

Department

Personal name



Funding Source

Organization

Japan Agency for Medical Research and Development

Organization

Division

Category of Funding Organization

Other

Nationality of Funding Organization

Japan


Other related organizations

Co-sponsor


Name of secondary funder(s)

Charitable Trust Mihara Cerebrovascular Disorder Research Promotion Fund


IRB Contact (For public release)

Organization

IRB, National Cerebral and Cardiovascular Center

Address

5-7-1 Fujishirodai, Suita, Osaka

Tel

06-6833-5012

Email

plandiv@ml.ncvc.go.jp


Secondary IDs

Secondary IDs

YES

Study ID_1

NCT02002325

Org. issuing International ID_1

U.S. National Institutes of Health

Study ID_2


Org. issuing International ID_2


IND to MHLW



Institutions

Institutions

帯広厚生病院(北海道)、中村記念病院(北海道)、秋田県立脳血管研究センター(秋田県)、山形市立病院済生館(山形県)、広南病院(宮城県)、新潟市民病院(新潟県)、美原記念病院(群馬県)、順天堂大学医学部附属浦安病院(千葉県)、杏林大学(東京都)、虎の門病院(東京都)、日本医科大学(東京)、東京慈恵会医科大学付属病院(東京都)、昭和大学藤が丘病院(神奈川県)、聖マリアンナ医科大学(神奈川県)、東海大学(神奈川県)、北里大学(神奈川県)、トヨタ記念病院(愛知県)、名古屋第二赤十字病院(愛知県)、岐阜大学(岐阜県)、京都第二赤十字病院(京都府)、兵庫医科大学(兵庫県)、神戸市立医療センター中央市民病院(兵庫県)、大西脳神経外科病院(兵庫県)、川崎医科大学(岡山県)、川崎医科大学附属川崎病院(岡山県)、徳島大学(徳島県)小倉記念病院(福岡県)、製鐵記念八幡病院(福岡県)、福岡赤十字病院(福岡県)、国立病院機構九州医療センター(福岡県)、長崎大学病院(長崎県)、済生会熊本病院(熊本県)、熊本赤十字病院(熊本県)、武蔵野赤十字病院(東京都)、岩手県立中央病院(岩手県)、国立病院機構京都医療センター(京都府)、聖マリアンナ医科大学東横病院(神奈川県)、佐賀大学(佐賀県)、山陰労災病院(鳥取県)、国立病院機構鹿児島医療センター(鹿児島県)、藤田保健衛生大学(愛知県)、国立循環器病研究センター(大阪府)


Other administrative information

Date of disclosure of the study information

2013 Year 09 Month 09 Day


Related information

URL releasing protocol

http://www.ncbi.nlm.nih.gov/pubmed/25088843?dopt=Abstract

Publication of results

Published


Result

URL related to results and publications

https://thaws.stroke-ncvc.jp/

Number of participants that the trial has enrolled

131

Results

131 patients were enrolled until July 2018.

Primary outcome: Favorable outcome (mRS 0-1) was comparable between the alteplase group (32/68, 47.1%) and the control group (28/58, 48.3%; relative risk (RR), 0.97 (95% CI, 0.68-1.41); P=0.892).

Safety outcomes: Symptomatic intracranial hemorrhage within 22 to 36 hours occurred in 1/71 and 0/60 (RR, infinity (95% CI, 0.06 to infinity); P>0.999), respectively. Death at 90 days occurred in 2/71 and 2/60 (RR, 0.85 (95% CI, 0.06-12.58); P>0.999), respectively.

Results date posted

2019 Year 03 Month 11 Day

Results Delayed


Results Delay Reason


Date of the first journal publication of results

2020 Year 04 Month 04 Day

Baseline Characteristics

Alteplase group (n=70): 73.2+/-12.4 years old, 25 females (36%), 53 wake-up strokes (76%), median initial NIHSS 7 (IQR 4-13), last known well to randomization time: median 10.2 hours (IQR 8.2-12.2)
Control group (n=61): 75.8+/-11.9 years old, 30 females (49%), 40 wake-up strokes (66%), median initial NIHSS 7 (IQR 5-12), last known well to randomization time: median 10.3 hours (IQR 7.7-11.8)

Participant flow

Following the early stop and positive results of the WAKE-UP trial, the THAWS steering committee suspended further enrollments on July 10, 2018. A total of 131 patients underwent randomization, as compared with the targeted enrollment of 300 patients. Of the 131 enrolled patients, 70 were assigned to the alteplase group and 61 to the control group

Adverse events

In the alteplase group, 9 patients (12.7%) experienced a serious adverse event, as compared with 6 patients (10%) in the control group (P=0.632).

Outcome measures

Primary outcome: Favorable outcome (mRS 0-1) was comparable between the alteplase group (32/68, 47.1%) and the control group (28/58, 48.3%; relative risk (RR), 0.97 (95% CI, 0.68-1.41); P=0.892).

Safety outcomes: Symptomatic intracranial hemorrhage within 22 to 36 hours occurred in 1/71 and 0/60 (RR, infinity (95% CI, 0.06 to infinity); P>0.999), respectively. Death at 90 days occurred in 2/71 and 2/60 (RR, 0.85 (95% CI, 0.06-12.58); P>0.999), respectively.

Plan to share IPD


IPD sharing Plan description



Progress

Recruitment status

Completed

Date of protocol fixation

2013 Year 11 Month 30 Day

Date of IRB

2013 Year 05 Month 10 Day

Anticipated trial start date

2014 Year 05 Month 01 Day

Last follow-up date

2018 Year 09 Month 19 Day

Date of closure to data entry

2018 Year 12 Month 04 Day

Date trial data considered complete

2019 Year 01 Month 21 Day

Date analysis concluded

2019 Year 03 Month 31 Day


Other

Other related information

PUBLICATIONS
1. Koga M, Yamamoto H, Inoue M, et al: Thrombolysis with alteplase at 0.6 mg/kg for stroke with unknown time of onset: a randomized controlled trial. Stroke. 2020;51(5):1530-1538. (main results)

2. Toyoda K, Inoue M, Yoshimura S, et al: Magnetic Resonance Imaging-Guided Thrombolysis (0.6 mg/kg) Was Beneficial for Unknown Onset Stroke Above a Certain Core Size: THAWS RCT Substudy. Stroke. 2020 Dec 10:STROKEAHA120030848. doi: 10.1161/STROKEAHA.120.030848. Online ahead of print. (subanalysis)

3. Thomalla G, Boutitie F, Ma H, Koga M, et al: Intravenous alteplase for stroke with unknown time of onset guided by advanced imaging: systematic review and meta-analysis of individual patient data. Lancet. 2020 Nov 14;396(10262):1574-1584 (IPD meta-analysis including THAWS)


Management information

Registered date

2013 Year 09 Month 02 Day

Last modified on

2020 Year 12 Month 15 Day



Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000011778


Research Plan
Registered date File name
2020/12/15 THAWS,Protocol,IJS2014.pdf

Research case data specifications
Registered date File name

Research case data
Registered date File name