AStudy To Evaluate Safety And Eficacy Of Apixaban In Japanese Acute Deep Vein Thrombosis (DVT) And Pulmonary Embolism (PE) Patients

Active-control, Multicenter, Randomized, Open-label, Safety And Efficacy Study Evaluating The Use Of Apixaban In The Treatment Of Symptomatic Deep Vein Thrombosis And Pulmonary Embolism In Japanese

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01780987

Enrollment

Registered

2013-01-31

Start date

2013-01-31

Completion date

2014-09-30

Last updated

2016-06-23

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Deep Vein Thrombosis, Pulmonary Embolism

Keywords

DVT, PE, VTE

Brief summary

The purpose of this study is to investigate safety of apixaban in Japanese acute DVT/PE subjects when symptomatic DVT/PE subjects are treated with 10 mg BID apixaban for 7 days as initial therapy followed by 5 mg BID apixaban for 23 weeks as long-term therapy (total treatment period is 24 weeks)

Interventions

DRUGApixaban

10 mg BID for 7 days followed by 5 mg BID for 23 weeks (total 24 weeks)

DRUGUnfractionated Heparin (UFH)

Dosing adjustment based on APTT = 1.5-2.5 times the control value, and until INR ≥ 1.5 for 5 days or more

DRUGWarfarin

Dosing for 24 weeks to target INR range between 1.5-2.5

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

20 Years to No maximum

Healthy volunteers

Inclusion criteria

* Acute symptomatic proximal DVT with evidence of proximal thrombosis * Acute symptomatic PE with evidence of thrombosis in segmental or more proximal branches

Exclusion criteria

* Active bleeding or high risk for bleeding contraindicating treatment with UFH and a VKA. * Uncontrolled hypertension: systolic blood pressure \> 180 mm Hg or diastolic blood pressure \> 110 mm Hg * Subjects requiring dual anti-platelet therapy

Design outcomes

Primary

Measure	Time frame	Description
Number of Participants With Major Bleeding Events ［Per International Society on Thrombosis and Homeostasis (ISTH) Definition］ or Clinically Relevant Non-major (CRNM) Bleeding Events Adjudicated by Clinical Event Committee During the Treatment Period	Baseline to Week 24	Major bleeding event was defined as an acute clinically overt bleeding accompanied by a decrease in hemoglobin of 2 g/dL or more, a transfusion of 4 or more units of packed red blood cells (a unit of packed red blood cells equal to about 200 cc), or bleeding that occurred in critical sites (e.g. intracranial). Fatal bleeding was also defined as a major bleeding event. CRNM bleeding event was defined as an acute clinically overt bleeding that did not satisfy the definition of major bleeding and that led to either hospitalization, physician guided medical or surgical treatment for bleeding, or a change in antithrombotic therapy.

Secondary

Measure	Time frame	Description
Number of Participants With Adjudicated Recurrent Symptomatic Venous Thromboembolism (VTE) ［Nonfatal Deep Venous Thrombosis (DVT) or Nonfatal Pulmonary Embolism (PE)］ or VTE-Related Death During the Intended Treatment Period	Baseline to Week 24	VTE-related death was defined as a death caused by documented PE which was diagnosed with objective testing or autopsy, or an unexplained death for which DVT/PE could not be ruled out as the cause. Intended Treatment Period was the period starting on the day of randomization and ending at either 2 days after the last dose of the study drug or Day 168/Week 24, whichever came late.
Number of Participants With Adjudicated Thrombotic Burden Worsened in Acute Symptomatic Proximal Deep Venous Thrombosis (DVT)	Baseline to Week 24	Computed tomography venography (CTV) and compression ultrasound (CUS) were used to assess thrombotic burden in the participants with DVT and the results were classified as improved, no change, or worsened. The timings of CTV and CUS examinations were at Week 12 and Weeks 2, 12 and 24.
Number of Participants With Adjudicated Thrombotic Burden Worsened in Acute Symptomatic Pulmonary Embolism (PE)	Baseline to Week 24	Computed tomography pulmonary angiography (CTPA) was used to assess thrombotic burden in the participants with PE and the results were classified as improved, no change, or worsened. The timings of CTPA examinations were Weeks 2, 12 and 24.
Number of Participants With Adjudicated Major Bleeding Events ［Per International Society on Thrombosis and Homeostasis (ISTH) Definition］During the Treatment Period	Baseline to Week 24	Major bleeding event was defined as an acute clinically overt bleeding accompanied by a decrease in hemoglobin of 2 g/dL or more, a transfusion of 4 or more units of packed red blood cells (a unit of packed red blood cells equal to about 200 cc), or bleeding that occurred in critical sites (e.g. intracranial). Fatal bleeding was also defined as a major bleeding event.
Number of Participants With Adjudicated All Bleeding Events During the Treatment Periods	Baseline to Week 24	All bleeding events consisted of major bleeding (per Interactional Society on Thrombosis and Homeostasis ［ISTH］ Definition), clinically relevant non-major (CRNM) and minor bleeding. All acute clinically overt bleeding events not meeting the criteria for either major bleeding or CRMN bleeding were classified as minor bleeding.

Countries

Japan

Participant flow

Participants by arm

Arm	Count
Apixaban Two apixaban 5 mg tablets were administrated twice a day (morning and evening) for 7 days followed by one apixaban 5 mg tablet administrated twice a day (morning and evening) for 23 weeks.	40
Unfractionated Heparin (UFH)/Warfarin UFH was administrated by continuous intravenous infusion to bring the activated partial thromboplastin time (APTT) to between 1.5 and 2.5 times the control level, until the effect of warfarin stabilized. UFH was administrated at least 5 days unless international normalized ratio (INR) ≥ 2.0 was reached before Day 5. The appropriate dose of warfarin potassium to achieve the target INR range between 1.5 and 2.5 was administrated for 24 weeks.	40
Total	80

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Adverse Event	0	4
Overall Study	Changing Residence	1	0
Overall Study	Not Receiving any Study Medication	0	1
Overall Study	Request of Changing Hospital	0	1
Overall Study	Withdrawal by Subject	2	0

Baseline characteristics

Characteristic	Unfractionated Heparin (UFH)/Warfarin	Total	Apixaban
Age, Continuous	66.1 years STANDARD_DEVIATION 17.72	65.2 years STANDARD_DEVIATION 15.64	64.3 years STANDARD_DEVIATION 13.4
Primary Diagnosis, Deep Venous Thrombosis (DVT)/Pulmonary Embolism (PE) DVT	23 participants	45 participants	22 participants
Primary Diagnosis, Deep Venous Thrombosis (DVT)/Pulmonary Embolism (PE) PE	17 participants	35 participants	18 participants
Sex: Female, Male Female	23 Participants	41 Participants	18 Participants
Sex: Female, Male Male	17 Participants	39 Participants	22 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	29 / 40	34 / 39
serious Total, serious adverse events	3 / 40	7 / 39

Outcome results

Primary

Number of Participants With Major Bleeding Events ［Per International Society on Thrombosis and Homeostasis (ISTH) Definition］ or Clinically Relevant Non-major (CRNM) Bleeding Events Adjudicated by Clinical Event Committee During the Treatment Period

Major bleeding event was defined as an acute clinically overt bleeding accompanied by a decrease in hemoglobin of 2 g/dL or more, a transfusion of 4 or more units of packed red blood cells (a unit of packed red blood cells equal to about 200 cc), or bleeding that occurred in critical sites (e.g. intracranial). Fatal bleeding was also defined as a major bleeding event. CRNM bleeding event was defined as an acute clinically overt bleeding that did not satisfy the definition of major bleeding and that led to either hospitalization, physician guided medical or surgical treatment for bleeding, or a change in antithrombotic therapy.