Trial Outcomes & Findings for Superficial Vein Thrombosis (SVT) Treated With Rivaroxaban Versus Fondaparinux (NCT NCT01499953)

Last Updated: 2023-05-15

Results Overview

The primary efficacy outcome was the composite of death from any cause, symptomatic pulmonary embolism (confirmed by ventilation-perfusion scanning, helical computed tomography, pulmonary angiography, or autopsy), symptomatic deep vein thrombosis (confirmed by ultrasonography or venography), or symptomatic extension towards the saphenofemoral junction or symptomatic recurrence of superficial vein thrombosis (confirmed by ultrasonography) up to day 45.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

472 participants

Primary outcome timeframe

45 +/- 5 days

Results posted on

2023-05-15

Participant Flow

From 25th April 2012 through 18th February 2016, a total of 485 patients were screened at 23 study sites in Germany. Of them, 9 patients did not meet the eligibility criteria. For another 4 subjects, signatures either on informed consent form or data protection waiver were not provided and therefore, these 4 subjects were not included in the study.

472 patients were randomized to one of the two treatment groups. One patient in the fondaparinux group withdrew consent after randomization but before the first study drug administration.

Participant milestones

Participant milestones
Measure	Fondaparinux Fondaparinux for 45 days subcutaneous application: 2,5 mg OD Fondaparinux: Fondaparinux Dose: 2.5 mg Duration: 45 (±5) days Frequency: once daily Application: subcutaneous	Rivaroxaban Rivaroxaban for 45 days oral dose: 10 mg OD Rivaroxaban: Dose: 10 mg Duration: 45 (±5) days Frequency: once daily Application: oral
Overall Study STARTED	236	236
Overall Study Participants Who Received at Least One Dose of Study Medication	235	236
Overall Study COMPLETED	226	222
Overall Study NOT COMPLETED	10	14

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Number of patients with specific risk factors was evaluated for the per protocol analysis set only.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Rivaroxaban n=236 Participants Rivaroxaban for 45 days oral dose: 10 mg OD Rivaroxaban: Dose: 10 mg Duration: 45 (±5) days Frequency: once daily Application: oral	Fondaparinux n=235 Participants Fondaparinux for 45 days subcutaneous application: 2,5 mg OD Fondaparinux: Fondaparinux Dose: 2.5 mg Duration: 45 (±5) days Frequency: once daily Application: subcutaneous	Total n=471 Participants Total of all reporting groups
Age, Continuous	60.7 years n=236 Participants	59.8 years n=235 Participants	60.3 years n=471 Participants
Sex: Female, Male Female	136 Participants n=236 Participants	148 Participants n=235 Participants	284 Participants n=471 Participants
Sex: Female, Male Male	100 Participants n=236 Participants	87 Participants n=235 Participants	187 Participants n=471 Participants
Race/Ethnicity, Customized Race · Caucasian	233 Participants n=236 Participants	234 Participants n=235 Participants	467 Participants n=471 Participants
Race/Ethnicity, Customized Race · Other	3 Participants n=236 Participants	1 Participants n=235 Participants	4 Participants n=471 Participants
Weight	86.2 kg n=236 Participants	88.0 kg n=235 Participants	87.1 kg n=471 Participants
Height	170 cm n=236 Participants	171 cm n=235 Participants	170 cm n=471 Participants
BMI	29.8 kg/m^2 n=236 Participants	30.2 kg/m^2 n=235 Participants	30.0 kg/m^2 n=471 Participants
Risk factors Age > 65 years	82 Participants n=211 Participants • Number of patients with specific risk factors was evaluated for the per protocol analysis set only.	84 Participants n=224 Participants • Number of patients with specific risk factors was evaluated for the per protocol analysis set only.	166 Participants n=435 Participants • Number of patients with specific risk factors was evaluated for the per protocol analysis set only.
Risk factors History of cancer or active cancer	16 Participants n=211 Participants • Number of patients with specific risk factors was evaluated for the per protocol analysis set only.	21 Participants n=224 Participants • Number of patients with specific risk factors was evaluated for the per protocol analysis set only.	37 Participants n=435 Participants • Number of patients with specific risk factors was evaluated for the per protocol analysis set only.
Risk factors Autoimmune disease	3 Participants n=211 Participants • Number of patients with specific risk factors was evaluated for the per protocol analysis set only.	4 Participants n=224 Participants • Number of patients with specific risk factors was evaluated for the per protocol analysis set only.	7 Participants n=435 Participants • Number of patients with specific risk factors was evaluated for the per protocol analysis set only.
Risk factors SVT of non-varicose vein	60 Participants n=211 Participants • Number of patients with specific risk factors was evaluated for the per protocol analysis set only.	72 Participants n=224 Participants • Number of patients with specific risk factors was evaluated for the per protocol analysis set only.	132 Participants n=435 Participants • Number of patients with specific risk factors was evaluated for the per protocol analysis set only.
Risk factors Male	89 Participants n=211 Participants • Number of patients with specific risk factors was evaluated for the per protocol analysis set only.	84 Participants n=224 Participants • Number of patients with specific risk factors was evaluated for the per protocol analysis set only.	173 Participants n=435 Participants • Number of patients with specific risk factors was evaluated for the per protocol analysis set only.
Risk factors History of DVT/PE/SVT	105 Participants n=211 Participants • Number of patients with specific risk factors was evaluated for the per protocol analysis set only.	106 Participants n=224 Participants • Number of patients with specific risk factors was evaluated for the per protocol analysis set only.	211 Participants n=435 Participants • Number of patients with specific risk factors was evaluated for the per protocol analysis set only.

PRIMARY outcome

Timeframe: 45 +/- 5 days

Population: Per protocol set

Outcome measures

Outcome measures
Measure	Rivaroxaban n=211 Participants Rivaroxaban for 45 days oral dose: 10 mg OD Rivaroxaban: Dose: 10 mg Duration: 45 (±5) days Frequency: once daily Application: oral	Fondaparinux n=224 Participants Fondaparinux for 45 days subcutaneous application: 2,5 mg OD Fondaparinux: Fondaparinux Dose: 2.5 mg Duration: 45 (±5) days Frequency: once daily Application: subcutaneous
Rate of Objectively Confirmed VTE Complications	7 Participants	4 Participants

SECONDARY outcome

Timeframe: 90 +/- 10 days

Population: Per protocol analysis set

For this, secondary efficacy outcomes were the composite primary efficacy outcome up to Day 90 and the following outcomes up to Day 45 and Day 90: each component of the primary efficacy outcome, the rate of major VTE (composite of symptomatic pulmonary embolism or symptomatic proximal DVT or VTE-related death) and the rates of surgery for SVT.

Outcome measures

Outcome measures
Measure	Rivaroxaban n=211 Participants Rivaroxaban for 45 days oral dose: 10 mg OD Rivaroxaban: Dose: 10 mg Duration: 45 (±5) days Frequency: once daily Application: oral	Fondaparinux n=224 Participants Fondaparinux for 45 days subcutaneous application: 2,5 mg OD Fondaparinux: Fondaparinux Dose: 2.5 mg Duration: 45 (±5) days Frequency: once daily Application: subcutaneous
Composite Primary Efficacy Outcome	15 Participants	15 Participants

SECONDARY outcome

Timeframe: 90 +/-10 days

Population: Per protocol set

composite of: * symptomatic pulmonary embolism * symptomatic proximal DVT * VTE-related death

Outcome measures

Outcome measures
Measure	Rivaroxaban n=211 Participants Rivaroxaban for 45 days oral dose: 10 mg OD Rivaroxaban: Dose: 10 mg Duration: 45 (±5) days Frequency: once daily Application: oral	Fondaparinux n=224 Participants Fondaparinux for 45 days subcutaneous application: 2,5 mg OD Fondaparinux: Fondaparinux Dose: 2.5 mg Duration: 45 (±5) days Frequency: once daily Application: subcutaneous
Rate of Major VTE Deep vein thrombosis	6 Participants	2 Participants
Rate of Major VTE Pulmonary embolism	0 Participants	0 Participants
Rate of Major VTE VTE-related death	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 90 +/-10 days

Population: Per protocol set

Outcome measures

Outcome measures
Measure	Rivaroxaban n=211 Participants Rivaroxaban for 45 days oral dose: 10 mg OD Rivaroxaban: Dose: 10 mg Duration: 45 (±5) days Frequency: once daily Application: oral	Fondaparinux n=224 Participants Fondaparinux for 45 days subcutaneous application: 2,5 mg OD Fondaparinux: Fondaparinux Dose: 2.5 mg Duration: 45 (±5) days Frequency: once daily Application: subcutaneous
Rates of Surgery for SVT	0 Participants	2 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 45 +/- 5 days

Population: Safety analysis set

* associated with a fall of hemoglobin of 2 g/l or more, or; * leading to a transfusion of 2 or more units of packed red blood cells or whole blood, or; * occurring into a critical site such as intracranial, intraspinal, intraocular, pericardial, intraarticular, intramuscular with compartment syndrome, retroperitoneal, or; * fatal bleeding.

Outcome measures

Outcome measures
Measure	Rivaroxaban n=236 Participants Rivaroxaban for 45 days oral dose: 10 mg OD Rivaroxaban: Dose: 10 mg Duration: 45 (±5) days Frequency: once daily Application: oral	Fondaparinux n=235 Participants Fondaparinux for 45 days subcutaneous application: 2,5 mg OD Fondaparinux: Fondaparinux Dose: 2.5 mg Duration: 45 (±5) days Frequency: once daily Application: subcutaneous
Major Bleeding (Main Safety Outcome)	0 Participants	0 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 45 +/- 5 days

Population: Safety analysis set

Clinically relevant, non-major bleeding is defined as any overt bleeding and * associated with a medical intervention, or * unscheduled contact with the physician (presence or telephone contact) * temporary or complete cessation of study drug * associated with any relevant discomfort to the patient (pain, impairment of activities of daily life)

Outcome measures

Outcome measures
Measure	Rivaroxaban n=236 Participants Rivaroxaban for 45 days oral dose: 10 mg OD Rivaroxaban: Dose: 10 mg Duration: 45 (±5) days Frequency: once daily Application: oral	Fondaparinux n=235 Participants Fondaparinux for 45 days subcutaneous application: 2,5 mg OD Fondaparinux: Fondaparinux Dose: 2.5 mg Duration: 45 (±5) days Frequency: once daily Application: subcutaneous
Clinically Relevant Non-major, Minor and Total (Any) Bleeding CRNM bleeding	6 Participants	1 Participants
Clinically Relevant Non-major, Minor and Total (Any) Bleeding Minor bleeding	15 Participants	15 Participants
Clinically Relevant Non-major, Minor and Total (Any) Bleeding Any bleeding	20 Participants	16 Participants

Adverse Events

Fondaparinux

Serious events: 3 serious events

Other events: 0 other events

Deaths: 0 deaths

Rivaroxaban

Serious events: 7 serious events

Other events: 0 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Fondaparinux n=235 participants at risk Fondaparinux for 45 days subcutaneous application: 2,5 mg OD Fondaparinux: Fondaparinux Dose: 2.5 mg Duration: 45 (±5) days Frequency: once daily Application: subcutaneous	Rivaroxaban n=236 participants at risk Rivaroxaban for 45 days oral dose: 10 mg OD Rivaroxaban: Dose: 10 mg Duration: 45 (±5) days Frequency: once daily Application: oral
Infections and infestations Suspected infection-associated seizure	0.00% 0/235 • Treatment-emergent adverse events are reported between first study drug administration until 5 days after last study drug administration.	0.42% 1/236 • Number of events 1 • Treatment-emergent adverse events are reported between first study drug administration until 5 days after last study drug administration.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung cancer	0.00% 0/235 • Treatment-emergent adverse events are reported between first study drug administration until 5 days after last study drug administration.	0.42% 1/236 • Number of events 1 • Treatment-emergent adverse events are reported between first study drug administration until 5 days after last study drug administration.
General disorders Mucosal bleeding	0.00% 0/235 • Treatment-emergent adverse events are reported between first study drug administration until 5 days after last study drug administration.	0.42% 1/236 • Number of events 1 • Treatment-emergent adverse events are reported between first study drug administration until 5 days after last study drug administration.
Cardiac disorders New onset of atrial fibrillation	0.00% 0/235 • Treatment-emergent adverse events are reported between first study drug administration until 5 days after last study drug administration.	0.42% 1/236 • Number of events 1 • Treatment-emergent adverse events are reported between first study drug administration until 5 days after last study drug administration.
Vascular disorders Worsening of arterial hypertension	0.00% 0/235 • Treatment-emergent adverse events are reported between first study drug administration until 5 days after last study drug administration.	0.42% 1/236 • Number of events 1 • Treatment-emergent adverse events are reported between first study drug administration until 5 days after last study drug administration.
Skin and subcutaneous tissue disorders Hemorrhagic allergic skin reaction	0.00% 0/235 • Treatment-emergent adverse events are reported between first study drug administration until 5 days after last study drug administration.	0.42% 1/236 • Number of events 1 • Treatment-emergent adverse events are reported between first study drug administration until 5 days after last study drug administration.
Vascular disorders Deep vein thrombosis	0.00% 0/235 • Treatment-emergent adverse events are reported between first study drug administration until 5 days after last study drug administration.	0.42% 1/236 • Number of events 1 • Treatment-emergent adverse events are reported between first study drug administration until 5 days after last study drug administration.
Infections and infestations Diabetic foot syndrome with tissue infection	0.43% 1/235 • Number of events 1 • Treatment-emergent adverse events are reported between first study drug administration until 5 days after last study drug administration.	0.00% 0/236 • Treatment-emergent adverse events are reported between first study drug administration until 5 days after last study drug administration.
Respiratory, thoracic and mediastinal disorders Hospitalisation for COPD exacerbation	0.43% 1/235 • Number of events 1 • Treatment-emergent adverse events are reported between first study drug administration until 5 days after last study drug administration.	0.00% 0/236 • Treatment-emergent adverse events are reported between first study drug administration until 5 days after last study drug administration.
Nervous system disorders Transient ischemic attack	0.43% 1/235 • Number of events 1 • Treatment-emergent adverse events are reported between first study drug administration until 5 days after last study drug administration.	0.00% 0/236 • Treatment-emergent adverse events are reported between first study drug administration until 5 days after last study drug administration.
Infections and infestations Sigmoid diverticulitis	0.43% 1/235 • Number of events 1 • Treatment-emergent adverse events are reported between first study drug administration until 5 days after last study drug administration.	0.00% 0/236 • Treatment-emergent adverse events are reported between first study drug administration until 5 days after last study drug administration.

Other adverse events

Adverse event data not reported

Additional Information

PD Dr. med. Jan Beyer-Westendorf

University Hospital Dresden, Centre for Vascular Medicine

Phone: +49-351-4582899

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place