Clinical Trial Results:
Superficial vein thrombosis (SVT) treated for forty-five days with Rivaroxaban versus Fondaparinux
Summary
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EudraCT number |
2011-005158-73 |
Trial protocol |
DE |
Global end of trial date |
31 Jul 2016
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Results information
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Results version number |
v1(current) |
This version publication date |
06 Jun 2022
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First version publication date |
06 Jun 2022
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
SURPRISE-2011
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01499953 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
GWT-TUD GmbH
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Sponsor organisation address |
Freiberger Str. 33, Dresden, Germany, 01067
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Public contact |
Medical Consulting, GWT-TUD GmbH, 0049 35125933100,
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Scientific contact |
Medical Consulting, GWT-TUD GmbH, 0049 35125933190,
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
10 May 2017
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
11 May 2016
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Global end of trial reached? |
Yes
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Global end of trial date |
31 Jul 2016
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
Evaluation of efficacy and safety of 45 days of rivaroxaban 10 mg vs. fondaparinux 2.5 mg in the treatment of superficial vein thrombosis of risk patients for major VTE complications to prove non-inferiority of oral rivaroxaban treatment
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Protection of trial subjects |
The conduct of this study was in compliance with the Good Clinical Practice Guidelines and under the guiding principles detailed in the Declaration of Helsinki. The study was also be carried out in keeping with applicable local law(s) and regulation(s). No specific measures had to be put in place as both substances (Rivaroxaban and Fondaparinux) have a wide therapeutic window. Therefore, in case of asymptomatic overdosing without overt bleeding complications, no specific treatment actions were required and the patient should have been kept under surveillance. For rivaroxaban, gastrointestinal uptake might have been reduced by activated carbon application within 3 hours after intake of rivaroxaban. In case of bleeding complications, study treatment with rivaroxaban and fondaparinux should have been interrupted or discontinued and symptomatic therapy (mechanical compression, surgical intervention, hemodynamic stabilization with fluids or whole-blood transfusions) should have been initiated as indicated.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
25 Apr 2012
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Germany: 472
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Worldwide total number of subjects |
472
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EEA total number of subjects |
472
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
282
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From 65 to 84 years |
168
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85 years and over |
22
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Recruitment
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Recruitment details |
From 25/04/2012 until 18/02/2016, 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. | ||||||||||||||||||||||||
Pre-assignment
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Screening details |
472 patients were randomized to one of the two treatment groups. One patient withdrew consent after randomization but before the first study drug administration. 448 subjects completed the study (222 rivaroxaban and 226 fondaparinux ). | ||||||||||||||||||||||||
Period 1
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Period 1 title |
overall trial (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | ||||||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Rivaroxaban | ||||||||||||||||||||||||
Arm description |
- | ||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||
Investigational medicinal product name |
Rivaroxaban
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Investigational medicinal product code |
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Other name |
Xarelto®
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Pharmaceutical forms |
Film-coated tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Patients taken rivaroxaban 10 mg once daily for 45 (±5) days at the same time.
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Arm title
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Fondaparinux | ||||||||||||||||||||||||
Arm description |
- | ||||||||||||||||||||||||
Arm type |
Active comparator | ||||||||||||||||||||||||
Investigational medicinal product name |
Fondaparinux
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Investigational medicinal product code |
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Other name |
Arixtra®
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Pharmaceutical forms |
Injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
Patients taken fondaparinux 2.5 mg once daily for 45 (±5) days at the same time.
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End points reporting groups
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Reporting group title |
Rivaroxaban
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Reporting group description |
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Reporting group title |
Fondaparinux
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Reporting group description |
- |
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End point title |
Rate of objectively confirmed VTE (venous thromboembolism) complications | ||||||||||||
End point description |
The primary efficacy outcome was the composite of death from any cause, symptomatic pulmonary embolism (PE), symptomatic deep vein thrombosis (DVT), or symptomatic extension towards the saphenofemoral junction, or symptomatic recurrence of superficial vein thrombosis (SVT) up to day 45.
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End point type |
Primary
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End point timeframe |
day 45
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Statistical analysis title |
Full Analysis | ||||||||||||
Comparison groups |
Rivaroxaban v Fondaparinux
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Number of subjects included in analysis |
435
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority | ||||||||||||
P-value |
= 0.0252 | ||||||||||||
Method |
Regression, Cox | ||||||||||||
Confidence interval |
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Adverse events information
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Timeframe for reporting adverse events |
day 0 (randomization) until day 90 (follow up)
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Adverse event reporting additional description |
Patients were asked at each visit whether they have experienced adverse events (AEs) or serious adverse events (SAEs). AEs were documented from the time of first IMP application until 5 days after the last application of study treatment. AEs and SAEs were listed by primary SOC (System Organ Class).
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
23.1
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Reporting groups
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Reporting group title |
Overall
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Reporting group description |
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Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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02 Mar 2012 |
Protocol 2.6 dated 10 Feb 2012: Change in labelling of the primary and secondary packaging; addition of composition of the DSMB |
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Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |