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Aspirin® Plus Rivaroxaban Versus Rivaroxaban Alone for the Prevention of Venous Stent Thrombosis in Patients With PTS (ARIVA)

Primary Purpose

Venous Thromboses, Stent Stenosis

Status
Suspended
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Aspirin 100mg
Sponsored by
University of Zurich
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Venous Thromboses focused on measuring Aspirin plus rivaroxaban vs. rivaroxaban for the prevention

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Signed informed consent form and data protection declaration obtained prior to any trial-specific procedures
  2. Patient aged ≥18 years
  3. Confirmed diagnosis of post-thrombotic syndrome defined as Villalta score > 4 points prior to enrolment and venous stent intervention
  4. Confirmed stenosis of inferior vena cava, iliac vein, or common femoral vein by duplex ultrasound or cross-sectional imaging (CT venography or MR venography) prior to enrolment and venous stent intervention
  5. Successfully conducted venous stent intervention involving either:

    • inferior vena cava
    • iliac vein or
    • common femoral vein
  6. Patients either on active treatment with rivaroxaban or patients planned for treatment with rivaroxaban after intervention

Exclusion Criteria:

  1. Previous venous intervention in target vessels
  2. Any contraindication for antithrombotic therapy (e.g. active gastric ulcer, duodenal ulcer, bleeding disorder with increased tendency of bleedings)
  3. Patients with a recent (3 months) clinically significant bleeding and / or active or recent (3 months) ulcerative or inflammatory gastrointestinal disease
  4. Ongoing antiplatelet therapy or previous antiplatelet therapy within 7 days prior to Visit 1
  5. Acute thrombosis (venous thromboembolism events < 3 months prior to Visit 1)
  6. Pre-existing coagulopathy
  7. Prior stroke or transient ischemic attack (< 12 months prior to Visit 1)
  8. Pregnancy, breast feeding, or planned pregnancy within the trial period or women of childbearing potential not using an adequate method of contraception
  9. Severe heart, liver or kidney disease
  10. Severe somatopathic, neurological and / or psychiatric disease(s)
  11. Malignant growth (concurrent or previous cancer with a relapse-free and treatment-free interval of less than 5 years before Visit 1)
  12. Known hypersensitivity to acetylsalicylic acid (Aspirin® cardio or Aspirin® protect and / or its excipients), to other antiphlogistic drugs or to analgesics or anti-fever drugs
  13. Concomitant intake of Methotrexat > 15 mg per week
  14. Parallel participation in another clinical trial, participation in a clinical trial within less than 6 weeks prior to the Screening visit or previous participation in this clinical trial
  15. Known to be, or suspected of being unable to comply with the trial protocol (e.g. no permanent address, history of drug abuse, known to be non-compliant or presenting an unstable psychiatric history)
  16. Legal incapacity and / or other circumstances rendering the patient unable to understand the nature, scope and possible impact of the study
  17. Custody by juridical or official order
  18. Evidence of an uncooperative attitude
  19. Difficulties in understanding the language in which the patient information is given
  20. Patients dependent from the investigator or sponsor (e.g. close relatives of the investigator, employees of the clinic, the sponsor or involved CRO(s))

Sites / Locations

  • Medizinische Universität Wien
  • Universitätsklinikum der RWTH Aachen
  • Klinikum Arnsberg - Karolinen Hospital
  • Universitätsklinikum Freiburg
  • Universitätsklinikum Heidelberg
  • University Hospital Zurich

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Aspirin®

Control group

Arm Description

To show if a combination therapy of rivaroxaban plus Aspirin® is more efficient (superiority testing) as rivaroxaban alone in the prevention of early venous stent thrombosis in patients suffering from post-thrombotic syndrome in the first 6 months following endovascular therapy. To demonstrate tolerability of combination therapy of Aspirin® plus rivaroxaban in long-term treatment.

Observational study of standard of care anticoagulation (rivarobaban dosis defined in the clinical routine).

Outcomes

Primary Outcome Measures

The primary patency rate is defined as the percentage of patients with primary treatment success after 6 months
The primary patency rate is defined as the percentage of patients with primary treatment success after 6 months (=Visit 3), i.e. without the occurrence of either i) occlusion of at least a part of the stent segment or ii.) a re-intervention to maintain patency of the treated segment.

Secondary Outcome Measures

Primary patency rate after 3 months
The primary patency rate is defined as the percentage of patients with primary treatment success after 3 months (=Visit 2), i.e. without the occurrence of either i) occlusion of at least a part of the stent segment or ii.) a re-intervention to maintain patency of the treated segment.
Secondary patency rate after 3 and 6 months
Secondary patency rate is defined as the percentage of patients with primary treatment success and without the occurrence of occlusion of at least a part of the stent segment, irrespective of any re-intervention
Primary sustained clinical success after 3 and 6 months (=Visit 2 and Visit 3)
Primary sustained clinical success, defined as the absence of post-thrombotic syndrome (Villalta score 0-4 points) without the need for repeated intervention assessed at the latest routine follow-up visit (at the latest available follow-up).
Difference between treatment groups in the incidence of patients with open stents but >50% residual stenosis according Duplex criteria
Difference between treatment groups in the incidence of patients with open stents but >50% residual stenosis according Duplex criteria
Difference of limb circumference
Difference of limb circumference of the affected leg in comparison to the contralateral leg at 3 and 6 months (= Visit 2 & 3), respectively, compared to baseline (for patients with only one affected leg)
Quality of life using the CIVIQ-20 (chronic venous insufficiency quality of life questionnaire)
Quality of life using the CIVIQ-20 (chronic venous insufficiency quality of life questionnaire) at 3 and 6 months (= Visit 2 & 3), respectively, compared to baseline. Value range: 20-100 points; Higher scores mean worse outcome
Change in Villalta score
Change in Villalta score with and without "ulcus cruris assessment" for the affected leg from baseline to 3 and 6 months (= Visit 2 & 3), respectively. Value range: 0-48 points; Higher scores mean worse outcome
Revised venous clinical severity score (rVCSS)
Revised venous clinical severity score (rVCSS) for the affected leg from baseline to 3 and 6 months (= Visit 2 & 3), respectively. Value range: 0-30 points; Higher scores mean worse outcome

Full Information

First Posted
October 14, 2019
Last Updated
September 8, 2023
Sponsor
University of Zurich
Collaborators
University Hospital Heidelberg, Medical University of Vienna, RWTH Aachen University, Klinikum Arnsberg, University Hospital Freiburg
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1. Study Identification

Unique Protocol Identification Number
NCT04128956
Brief Title
Aspirin® Plus Rivaroxaban Versus Rivaroxaban Alone for the Prevention of Venous Stent Thrombosis in Patients With PTS
Acronym
ARIVA
Official Title
Aspirin® Plus Rivaroxaban Versus Rivaroxaban Alone for the Prevention of Venous Stent Thrombosis in Patients With Post-thrombotic Syndrome a Multi-center, International, Randomized, Open Label, Controlled Trial
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Suspended
Why Stopped
Interims analysis
Study Start Date
March 11, 2020 (Actual)
Primary Completion Date
December 2023 (Anticipated)
Study Completion Date
June 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Zurich
Collaborators
University Hospital Heidelberg, Medical University of Vienna, RWTH Aachen University, Klinikum Arnsberg, University Hospital Freiburg

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
To show if a combination therapy of rivaroxaban plus Aspirin® is more efficient (superiority testing) as rivaroxaban alone in the prevention of early venous stent thrombosis in patients suffering from post-thrombotic syndrome in the first 6 months following endovascular therapy To demonstrate tolerability of combination therapy of Aspirin® plus rivaroxaban in long-term treatment.
Detailed Description
Deep vein thrombosis is associated with severe morbidity and mortality. It is the most frequent type of venous thromboembolism (VTE) and responsible for approximately 800.000 deaths per year in the European Union and the United States combined. The post-thrombotic syndrome (PTS) is a frequent long-term complication of proximal deep vein thrombosis (DVT), which occurs in up to 50% of patients despite adequate anticoagulation therapy and compression stockings. Patients with DVT of the inferior vena cava or iliac veins are at highest risk for the development of PTS. Inadequate recanalization and persistent venous outflow obstruction promotes the development of venous hypertension, secondary valve damage, valvular reflux, and the clinical manifestation of PTS, which consists of a similar set of signs and symptoms as in superficial venous insufficiency. Symptoms may include leg edema, pruritus, dysesthesia, leg pain on standing, skin changes, venous claudication with limited exercise capacity, and leg ulcers. Venous ulcers occur in approximately 10% of patients with iliofemoral DVT after 3 years. The diagnosis of PTS is made based on the presence of its clinical features, a prior history of proximal DVT, and the results of imaging studies. Clinical scores, such as the Villalta score, can function as a tool to stage severity of disease. PTS in classified as mild if the Villalta score is 5-9, moderate if the Villalta score is 10-14, and severe if the Villata score exceeds 15 points. Disabling venous claudication can be diagnosed by treadmill exercise tests. Magnetic resonance imaging venography can be used in addition to duplex ultrasound to objectify central venous obstruction, and unmark underlying strategic compression sides (e.g. May-Thurner syndrome). Recommendations by the American Heart Association for endovascular treatment of PTS suggest percutaneous recanalization including the implantation of stents for symptomatic patients) Endovascular therapy with provisional stent placement shows promising clinical outcomes to improve PTS-associated symptoms, including leg ulcers. However, there is significant risk for early stent thrombosis, estimated as high as 21% after 12 months. Antithrombotic therapy is the corner stone of the prevention of stent thrombosis, but there is great inconsistency in the use of antithrombotic agents. The value of extended anticoagulation therapy in PTS patients beyond the durations recommended in VTE management guidelines is controversial, and it has not been specifically investigated in the presence of venous stent implants. Although oral anticoagulants are accepted as the main therapy regimen, the benefit of antiplatelet therapy (APT) in the early phase after venous stent implantation is unclear. According to a recent international survey completed by 106 experts, one third reported to use life-long anticoagulation with a vitamin-K antagonist (VKA), and another 19% chose life-long anticoagulation with direct anticoagulant (DOAC) for a presented case scenario of a PTS patients treated with venous stents. The use of APT following stent placement alone or in combination with an anticoagulant was reported in 7% and 13%, respectively, whereas 25% reported use of APT following discontinuation of ACT. Conventionally, antiplatelet agents, such as acetylsalicylic acid, are regarded as drugs that prevent arterial thrombosis, as platelet adhesion predominates clotting in high-flow, high-sheer circulation. There is compelling evidence that Aspirin® is effective in the prevention of arterial stent thrombosis, but it is unclear, whether it can prevent venous stent thrombosis.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Venous Thromboses, Stent Stenosis
Keywords
Aspirin plus rivaroxaban vs. rivaroxaban for the prevention

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
a multi-center, international, randomized, open label, controlled trial
Masking
None (Open Label)
Allocation
Randomized
Enrollment
316 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Aspirin®
Arm Type
Experimental
Arm Description
To show if a combination therapy of rivaroxaban plus Aspirin® is more efficient (superiority testing) as rivaroxaban alone in the prevention of early venous stent thrombosis in patients suffering from post-thrombotic syndrome in the first 6 months following endovascular therapy. To demonstrate tolerability of combination therapy of Aspirin® plus rivaroxaban in long-term treatment.
Arm Title
Control group
Arm Type
No Intervention
Arm Description
Observational study of standard of care anticoagulation (rivarobaban dosis defined in the clinical routine).
Intervention Type
Drug
Intervention Name(s)
Aspirin 100mg
Other Intervention Name(s)
Aspirin
Intervention Description
Aspirin® cardio (CH) or Aspirin® protect (DE, AT) Film coated tablets Acetylsalicylic acid 100 mg Once daily oral intake for 6 months
Primary Outcome Measure Information:
Title
The primary patency rate is defined as the percentage of patients with primary treatment success after 6 months
Description
The primary patency rate is defined as the percentage of patients with primary treatment success after 6 months (=Visit 3), i.e. without the occurrence of either i) occlusion of at least a part of the stent segment or ii.) a re-intervention to maintain patency of the treated segment.
Time Frame
6 month
Secondary Outcome Measure Information:
Title
Primary patency rate after 3 months
Description
The primary patency rate is defined as the percentage of patients with primary treatment success after 3 months (=Visit 2), i.e. without the occurrence of either i) occlusion of at least a part of the stent segment or ii.) a re-intervention to maintain patency of the treated segment.
Time Frame
3 month
Title
Secondary patency rate after 3 and 6 months
Description
Secondary patency rate is defined as the percentage of patients with primary treatment success and without the occurrence of occlusion of at least a part of the stent segment, irrespective of any re-intervention
Time Frame
3 and 6 months
Title
Primary sustained clinical success after 3 and 6 months (=Visit 2 and Visit 3)
Description
Primary sustained clinical success, defined as the absence of post-thrombotic syndrome (Villalta score 0-4 points) without the need for repeated intervention assessed at the latest routine follow-up visit (at the latest available follow-up).
Time Frame
3 and 6 months
Title
Difference between treatment groups in the incidence of patients with open stents but >50% residual stenosis according Duplex criteria
Description
Difference between treatment groups in the incidence of patients with open stents but >50% residual stenosis according Duplex criteria
Time Frame
3 month
Title
Difference of limb circumference
Description
Difference of limb circumference of the affected leg in comparison to the contralateral leg at 3 and 6 months (= Visit 2 & 3), respectively, compared to baseline (for patients with only one affected leg)
Time Frame
3 and 6 months
Title
Quality of life using the CIVIQ-20 (chronic venous insufficiency quality of life questionnaire)
Description
Quality of life using the CIVIQ-20 (chronic venous insufficiency quality of life questionnaire) at 3 and 6 months (= Visit 2 & 3), respectively, compared to baseline. Value range: 20-100 points; Higher scores mean worse outcome
Time Frame
3 and 6 months
Title
Change in Villalta score
Description
Change in Villalta score with and without "ulcus cruris assessment" for the affected leg from baseline to 3 and 6 months (= Visit 2 & 3), respectively. Value range: 0-48 points; Higher scores mean worse outcome
Time Frame
3 and 6 months
Title
Revised venous clinical severity score (rVCSS)
Description
Revised venous clinical severity score (rVCSS) for the affected leg from baseline to 3 and 6 months (= Visit 2 & 3), respectively. Value range: 0-30 points; Higher scores mean worse outcome
Time Frame
3 and 6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Signed informed consent form and data protection declaration obtained prior to any trial-specific procedures Patient aged ≥18 years Confirmed diagnosis of post-thrombotic syndrome defined as Villalta score > 4 points prior to enrolment and venous stent intervention Confirmed stenosis of inferior vena cava, iliac vein, or common femoral vein by duplex ultrasound or cross-sectional imaging (CT venography or MR venography) prior to enrolment and venous stent intervention Successfully conducted venous stent intervention involving either: inferior vena cava iliac vein or common femoral vein Patients either on active treatment with rivaroxaban or patients planned for treatment with rivaroxaban after intervention Exclusion Criteria: Previous venous intervention in target vessels Any contraindication for antithrombotic therapy (e.g. active gastric ulcer, duodenal ulcer, bleeding disorder with increased tendency of bleedings) Patients with a recent (3 months) clinically significant bleeding and / or active or recent (3 months) ulcerative or inflammatory gastrointestinal disease Ongoing antiplatelet therapy or previous antiplatelet therapy within 7 days prior to Visit 1 Acute thrombosis (venous thromboembolism events < 3 months prior to Visit 1) Pre-existing coagulopathy Prior stroke or transient ischemic attack (< 12 months prior to Visit 1) Pregnancy, breast feeding, or planned pregnancy within the trial period or women of childbearing potential not using an adequate method of contraception Severe heart, liver or kidney disease Severe somatopathic, neurological and / or psychiatric disease(s) Malignant growth (concurrent or previous cancer with a relapse-free and treatment-free interval of less than 5 years before Visit 1) Known hypersensitivity to acetylsalicylic acid (Aspirin® cardio or Aspirin® protect and / or its excipients), to other antiphlogistic drugs or to analgesics or anti-fever drugs Concomitant intake of Methotrexat > 15 mg per week Parallel participation in another clinical trial, participation in a clinical trial within less than 6 weeks prior to the Screening visit or previous participation in this clinical trial Known to be, or suspected of being unable to comply with the trial protocol (e.g. no permanent address, history of drug abuse, known to be non-compliant or presenting an unstable psychiatric history) Legal incapacity and / or other circumstances rendering the patient unable to understand the nature, scope and possible impact of the study Custody by juridical or official order Evidence of an uncooperative attitude Difficulties in understanding the language in which the patient information is given Patients dependent from the investigator or sponsor (e.g. close relatives of the investigator, employees of the clinic, the sponsor or involved CRO(s))
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nils Kucher, Prof.Dr.med.
Organizational Affiliation
University Hospital, Zürich
Official's Role
Study Chair
Facility Information:
Facility Name
Medizinische Universität Wien
City
Wien
ZIP/Postal Code
1090
Country
Austria
Facility Name
Universitätsklinikum der RWTH Aachen
City
Aachen
ZIP/Postal Code
52074
Country
Germany
Facility Name
Klinikum Arnsberg - Karolinen Hospital
City
Arnsberg
ZIP/Postal Code
59759
Country
Germany
Facility Name
Universitätsklinikum Freiburg
City
Bad Krozingen
ZIP/Postal Code
79189
Country
Germany
Facility Name
Universitätsklinikum Heidelberg
City
Heidelberg
ZIP/Postal Code
69120
Country
Germany
Facility Name
University Hospital Zurich
City
Zürich
ZIP/Postal Code
8091
Country
Switzerland

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Aspirin® Plus Rivaroxaban Versus Rivaroxaban Alone for the Prevention of Venous Stent Thrombosis in Patients With PTS

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