UMIN-CTR Clinical Trial

Public title

Evaluation of rivaroxaban for distal deep vein thrombosis - a single-center, randomized, open-label, assessor-blind, parallel group, exploratory study

Acronym

ISE calf DVT study

Scientific Title

Evaluation of rivaroxaban for distal deep vein thrombosis - a single-center, randomized, open-label, assessor-blind, parallel group, exploratory study

Scientific Title:Acronym

ISE calf DVT study

Region

Japan

Condition

distal deep vein thrombosis

Classification by specialty

Cardiology	Vascular surgery	Cardiovascular surgery
Adult

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

The objective of this study is to investigate the usefulness of anticoagulant treatment with rivaroxaban in patients with newly diagnosed distal deep vein thrombosis (DVT), who has a risk of thrombus extension.

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Exploratory

Trial characteristics_2

Explanatory

Developmental phase

Not applicable

Primary outcomes

Composite endpoint of asymptomatic proximal DVT, symptomatic proximal DVT, symptomatic non-fatal PE or fatal PE, within 90 days after starting the study

Key secondary outcomes

1) Occurrences of recurrent distal DVT within 90 days after starting the study
2) Occurrences of symptomatic proximal DVT within 90 days after starting the study
3) Occurrences of asymptomatic proximal DVT within 90 days after starting the study
4) Occurrences of symptomatic pulmonary embolism (PE) (fatal or non-fatal) within 90 days after starting the study
5) Composite of 1) -4)
6) Occurrences of recurrent distal DVT within 120, 180, and 365 days after starting the study
7) Occurrences of symptomatic proximal DVT within 120, 180, and 365 days after starting the study
8) Occurrences of asymptomatic proximal DVT within 120, 180, and 365 days after starting the study
9) Occurrences of symptomatic PE (fatal or non-fatal) within 120, 180, and 365 days after starting the study
10) Composite of 6) -9)
11) Composite of 7) -9)
12) Change in thrombus volume in 8, 21, and 90 days after starting the study
13) Biomarkers related to fibrinolytic and coagulation system (D dimer, SF)
14) Occurrences of *clinically relevant bleeding events within 90, 120, 180, and 365 days after starting the study
*clinically relevant bleeding events: composite endpoint of major bleeding events or other clinically relevant non-major bleeding events
15) Composite of asymptomatic proximal DVT, symptomatic proximal DVT, symptomatic PE (fatal or non-fatal), or clinically relevant bleeding events within 90, 120, 180, and 365 days after starting the study
16) Composite of asymptomatic proximal DVT, symptomatic proximal DVT, symptomatic PE (fatal or non-fatal), or major bleeding events within 90, 120, 180, and 365 days after starting the study

Study type

Interventional

Basic design

Parallel

Randomization

Randomized

Randomization unit

Individual

Blinding

Open -but assessor(s) are blinded

Control

Active

Stratification

YES

Dynamic allocation

YES

Institution consideration

Institution is not considered as adjustment factor.

Blocking

NO

Concealment

Central registration

No. of arms

2

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

Rivaroxaban and physical treatment group
Rivaroxaban 15 mg tablets shall be orally administered after meal twice daily for 21 days after starting treatment (initial treatment period).Subsequently, the dosage shall be reduced to 15 mg tablet once daily for 69 days(maintenance period).If a bleeding risk is concerned in the initial treatment period, the dosage can be reduced to 15 mg tablet once daily according to the judgment by the physician.
In addition, the physical therapy including wearing an elastic stocking or an elastic wrap shall be thoroughly instructed.

Interventions/Control_2

Physical treatment group
The physical therapy including wearing an elastic stocking or an elastic wrap shall be thoroughly instructed.

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

Not applicable

Gender

Male and Female

Key inclusion criteria

Male and female patients who have been newly diagnosed with distal DVT by CUS shall meet the following criteria:
(1) Male and female patients whose age is 20 years or older.
(2) A written consent has been obtained
(3) Patients who have at least one of the following risks for extending distal DVT which are listed in the 9th edition of ACCP guidelines:
a) Associated with swelling/pain
b) D-dimer positive
c) Thrombosis that is extensive, or close to the popliteal veins
d) Having an active malignant disease
e) Having a medical history of proximal DVT or PE
f) Being hospitalized
g) Idiopathic

Key exclusion criteria

1) A patient who was allocated in this study previously
2) A patient who has already started an anticoagulant treatment including preventive medications for postoperative DVT at the orthopedic department etc.
3) A patient who has other diseases than DVT, which anticoagulants are indicated for
4) A patient who is not applicable for wearing an elastic stocking or an elastic wrap
5) A patient who has a medical history of hypersensitivity against rivaroxaban
6) A patient who has severe renal impairment [estimated creatinine clearance (CLCR) <30 ml/min: calculated from Cockcroft-Gault formula]
7) A patient with active bleeding
8) A patient who has hepatic impairment of Child-Pugh classification B and C
9) A pregnant or potentially pregnant female or a nursing female
*Pregnancy shall be checked by hearing consultation. Even with a slight suspicion, the patient shall be excluded.
10) A patient who has been on a HIV protease inhibitor*
11) A patient who has been on a Cobicistat-containing product*
12) A patient who has been on an oral or injectable azole antifungal drug*
13) A patient who is suffering acute bacterial endocarditis
14) A patient who received a CNS surgery recently or has a cerebral hemorrhage which developed recently
15) A patient who has acute symptomatic PE, or acute proximal DVT with or without symptoms
16) A patient who has serious complications, of which life prognosis is considered to be <3 months
17) A patient who has uncontrolled hypertension (systolic pressure >180 mmHg or diastolic pressure >110 mmHg)
18) A patient who has participated in any clinical trials of other drugs or medical devices within 30 days prior to randomization
19) A patient who is not able to comply with series of processes related to the clinical study

Target sample size

150

Name of lead principal investigator

1st name
Middle name
Last name	Masaaki Ito

Organization

Mie University Graduate School of Medicine

Division name

Department of Cardiology and Nephrology

Zip code

Address

2-174, Edobashi, Tsu, Mie

TEL

059-231-5015

Email

mitoka@clin.medic.mie-u.ac.jp

Name of contact person

1st name
Middle name
Last name	Yoshito Ogihara

Organization

Mie University Graduate School of Medicine

Division name

Department of Cardiology and Nephrology

Zip code

Address

2-174, Edobashi, Tsu, Mie

TEL

059-231-5015

Homepage URL

Email

yoshito@clin.medic.mie-u.ac.jp

Institute

Mie University Graduate School of Medicine
Department of Cardiology and Nephrology

Institute

Department

Personal name

Organization

Bayer Yakuhin, Ltd

Organization

Division

Category of Funding Organization

Profit organization

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

Address

Tel

Email

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

三重大学医学部附属病院(三重県)

Date of disclosure of the study information

2017

Year

07

Month

06

Day

URL releasing protocol

Publication of results

Unpublished

URL related to results and publications

Number of participants that the trial has enrolled

Results

Results date posted

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Participant flow

Adverse events

Outcome measures

Plan to share IPD

IPD sharing Plan description

Recruitment status

Terminated

Date of protocol fixation

2017

Year

07

Month

01

Day

Date of IRB

Anticipated trial start date

2018

Year

04

Month

02

Day

Last follow-up date

2019

Year

07

Month

31

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2017

Year

07

Month

06

Day

Last modified on

2017

Year

09

Month

13

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000032126