UMIN-CTR Clinical Trial

Public title

Clot regression effects of rivaroxaban in treatment of venous thromboembolism in cancer patients.

Acronym

Clot regression effects of rivaroxaban in treatment of venous thromboembolism in cancer patients.

Scientific Title

Clot regression effects of rivaroxaban in treatment of venous thromboembolism in cancer patients.

Scientific Title:Acronym

Clot regression effects of rivaroxaban in treatment of venous thromboembolism in cancer patients.

Region

Japan

Condition

Venous thromboembolism

Classification by specialty

Cardiology

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

To study the clot regression effects of rivaroxaban in cancer patients who developed venous thromboembolism (VTE) such as deep vein thrombosis (DVT) or pulmonary embolism (PE).

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Trial characteristics_2

Developmental phase

Primary outcomes

Clot regression evaluated by contrast-enhanced CT imaging (Imaging is performed at baseline, 3 weeks and 3 months days after initiation of treatment).The ratio of clot volume regression after 3 weeks or 3 months compared with the clot volume at baseline is investigated. In addition, the rate of normalization (no thrombus in legs and lungs) is also investigated.

Key secondary outcomes

1)Recurrence of symptomatic DVT or PE
2)Hemorrhagic complications
Major bleeding:Clinically definite reduction in Hb by 2.0 g/dL or more, Bleeding requiring 2 units or more of transfusion, Intracranial hemorrhage, retroperitoneal hemorrhage, and bleeding to death
Non-major bleeding: Bleeding clinically associated with rivaroxaban not meeting the criteria for major bleeding

Study type

Interventional

Basic design

Single arm

Randomization

Non-randomized

Randomization unit

Blinding

Open -no one is blinded

Control

Uncontrolled

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

No. of arms

1

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

VTE patients receive the NHI-covered standard rivaroxaban treatment (30 mg/day for 3 weeks after initiation of treatment, followed by 15 mg/day).

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

Age-lower limit

20

years-old

<=

Age-upper limit

75

years-old

>

Gender

Male and Female

Key inclusion criteria

Patients aged 20 to 75 years, with active cancer at diagnosis with VTE. Active cancer at baseline was defined as a diagnosis of cancer that occurred within 6 months before enrollment, any treatment for cancer within the previous 6 months, or recurrent or metastatic cancer.

Key exclusion criteria

Patients contraindicated for rivaroxaban, with creatinine clearance <30 mL/min, with isolated distal DVT, within 6 months in the remaining days, with a vitamin K antagonist, with severe complication (significant liver disease, active bleeding or a high risk of bleeding contraindicating anticoagulant treatment, severe hypertension (a systolic blood pressure of more than 180 mm Hg or a diastolic blood pressure of more than 110 mm Hg)), pregnancy, and breast-feeding. Patients who the physician in charge judges are ineligible for the present study.

Target sample size

40

Name of lead principal investigator

1st name	Satoaki
Middle name
Last name	Matoba

Organization

Kyoto Prefectural University of Medicine

Division name

Department of Cardiovascular Medicine

Zip code

6028566

Address

465 Kajii-cho Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan

TEL

075-251-5511

Email

matoba@koto.kpu-m.ac.jp

Name of contact person

1st name	Naohiko
Middle name
Last name	Nakanishi

Organization

Kyoto Prefectural University of Medicine

Division name

Department of Cardiovascular Medicine

Zip code

6028566

Address

465 Kajii-cho Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan

TEL

075-251-5511

Homepage URL

Email

naka-nao@koto.kpu-m.ac.jp

Institute

Kyoto Prefectural University of Medicine

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

Kyoto Prefectural University of Medicine

Address

465 Kajii-cho Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan

Tel

075-251-5337

Email

rinri@koto.kpu-m.ac.jp

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

Date of disclosure of the study information

2017

Year

06

Month

17

Day

URL releasing protocol

https://bmjopen.bmj.com/content/9/11/e031698.long

Publication of results

Published

URL related to results and publications

https://www.nature.com/articles/s41598-022-26150-w

Number of participants that the trial has enrolled

40

Results

This study revealed that rivaroxaban had a sufficient clot-regression effect for the treatment of VTE in cancer patients. It exhibited an acceptable safety profile; however, future clinical use in patients with gastrointestinal or genitourinary cancers should be met with caution.

Results date posted

2022

Year

12

Month

31

Day

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

The mean age of the 40 patients included in the study was 61.9 years, and 55% were male. The mean body mass index (BMI) was 23.8. 72.5% of patients had pulmonary thromboembolism, and the mean pulmonary embolism severity index (PESI) score was 107, corresponding to a high risk of 30-day mortality. About one-fourth (27.5%) of patients had deep vein thrombosis only; 30% had hepatic dysfunction, but renal function was relatively preserved. No patients received antiplatelet therapy or had a known thrombophilia. Regarding bleeding risk, the mean HAS-BLED score was 1.2. In terms of cancer type, 45% of the patients had gastrointestinal cancers and 22.5% had genitourinary cancers.

Participant flow

Due to the COVID-19 pandemic, the pace of enrollment was slower than planned, forcing an extension of the study period. The Kyoto Prefectural University of Medicine Hospital accounted for 32 cases (80%), with 32 cases, while the other facilities were as follows: Kyoto Prefectural University of Medicine Northern Medical Center, 1 case; Kyoto Municipal Hospital, 3 cases; Kyoto First Red Cross Hospital, 2 cases; and Kyoto Second Red Cross Hospital, 2 cases. Protocol treatment was completed in 25 patients, and protocol treatment was terminated early in 15 patients (37.5%), mostly due to adverse events (10 patients). CT scans to assess the primary endpoint of rivaroxaban thrombus regression were performed in 36 patients after 3 weeks of treatment and in 26 patients after 3 months of treatment.

Adverse events

Of the 40 patients, 14 (35%) had adverse events, 9 were related to rivaroxaban, 7 (17.5%) had serious adverse events, including 2 hepatic dysfunction, 1 gastrointestinal bleeding, 1 anemia, 1 ileus, 1 contrast medium allergy, and 1 pseudoaneurysm. aneurysm. No treatment-related deaths were observed.

Outcome measures

Total thrombus volume was reduced after 3 weeks (2.89 cm3; 0 to 54.62 cm3) and 3 months (0.11 cm3; 0 to 1.38 cm3) of rivaroxaban treatment compared to baseline (11.00 cm3; 0.05 to 142.25 cm3). The thrombus regression effect continued after the rivaroxaban dose was reduced to 15 mg. The primary endpoint of thrombus regression rate was 83.1% (95% CI, 73.9-92.3%) at 3 weeks and 98.7% (95% CI, 97.1-100.0%) at 3 months. This was statistically significant clot regression at both 3 weeks and 3 months after rivaroxaban treatment. Sensitivity analyses accounting for dropout showed significant differences in clot regression rates of 74.7% (95% CI, 63.2-86.3%) and 64.1% (95% CI, 48.9-79.4%), respectively. Additionally, complete thrombus resolution was achieved in 36.1% and 80.8% of patients at 3 weeks and 3 months, respectively.
Recurrent symptomatic VTE and bleeding complications were evaluated as secondary endpoints. Of the 40 patients who received protocol treatment, only one patient had a recurrence of VTE during rivaroxaban treatment. Regarding safety, bleeding complications occurred in 12.5% of patients at 3 weeks and 15.2% at 3 months (p = 0.50). In total, seven patients had major bleeding. However, no fatal bleeding was observed during the 3-month study period. Gastrointestinal bleeding was most common, but there was no significant difference between the intensive high-dose and low-dose periods of rivaroxaban (5.0% vs. 6.0%, p = 0.61). 1 patient had traumatic intracranial bleeding. In addition, three weeks of intensive high-dose rivaroxaban did not increase minor bleeding compared with three months of low-dose rivaroxaban (2.5% vs 9.0%, p = 0.23).

Plan to share IPD

IPD sharing Plan description

Recruitment status

Completed

Date of protocol fixation

2017

Year

06

Month

16

Day

Date of IRB

2018

Year

06

Month

04

Day

Anticipated trial start date

2018

Year

07

Month

01

Day

Last follow-up date

2021

Year

03

Month

31

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2017

Year

06

Month

16

Day

Last modified on

2022

Year

12

Month

31

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000031850