UMIN-CTR Clinical Trial

Basic information
Official scientific title of the study	Evaluation of rivaroxaban for distal deep vein thrombosis - a single-center, randomized, open-label, assessor-blind, parallel group, exploratory study
Title of the study (Brief title)	ISE calf DVT study
Region	Japan

Condition
Condition	distal deep vein thrombosis
Classification by specialty	Cardiology Vascular surgery Cardiovascular surgery Adult
Classification by malignancy	Others
Genomic information	NO

Objectives
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

Assessment
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

Base
Study type	Interventional

Study design
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

Intervention
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

Eligibility
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

Research contact person
Name of lead principal investigator	Masaaki Ito
Organization	Mie University Graduate School of Medicine
Division name	Department of Cardiology and Nephrology
Address	2-174, Edobashi, Tsu, Mie
TEL	059-231-5015
Email	mitoka@clin.medic.mie-u.ac.jp

Public contact
Name of contact person	Yoshito Ogihara
Organization	Mie University Graduate School of Medicine
Division name	Department of Cardiology and Nephrology
Address	2-174, Edobashi, Tsu, Mie
TEL	059-231-5015
Homepage URL
Email	yoshito@clin.medic.mie-u.ac.jp

Sponsor
Institute	Mie University Graduate School of Medicine Department of Cardiology and Nephrology
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)

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	三重大学医学部附属病院(三重県)

Other administrative information
Date of disclosure of the study information	2017 Year 07 Month 06 Day

Progress
Recruitment status	Terminated
Date of protocol fixation	2017 Year 07 Month 01 Day
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

Related information
URL releasing protocol
Publication of results	Unpublished
URL releasing results
Results
Other related information

Management information
Registered date	2017 Year 07 Month 06 Day
Last modified on	2017 Year 09 Month 13 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000032126