Rivaroxaban for Scheduled Work-up of DVT - The Ri-Schedule Study (Ri-Schedule)

Rivaroxaban for Scheduled Work-up of Patients With Suspected Deep Venous Thrombosis

This prospective outcome study is designed to assess the safety of rivaroxaban in the pre-diagnosis phase of DVT.

Study Overview

• Status: Completed
• Conditions: Deep Venous Thrombosis
• Intervention / Treatment: Drug: Rivaroxaban

Detailed Description

This prospective outcome study is designed to assess the safety of rivaroxaban in the pre-diagnosis phase of DVT.

International guidelines suggest the use of low molecular weight heparin (LMWH) if the diagnostic process is expected to be delayed for more than 4 hours.

Rivaroxaban is a new DOAC that in clinical trials has proven to be non-inferior to LMWH and warfarin for the treatment of DVT with the added benefit of causing less major bleeding.

Because of its rapid onset of action and oral administration, rivaroxaban could be used instead of LMWH in the pre-diagnosis phase pending the results of the diagnostic test. However, the safety of a such proposed indication has to be proven before it can be adopted in clinical practice.

This study aims to determine the safety and feasibility of pre-diagnostic treatment with rivaroxaban. The primary outcome of this study "safety" is a composite endpoint of serious bleedings encountered within 48 hours after administration of rivaroxaban.

• Study Type: Interventional
• Enrollment (Actual): 625
• Phase: Phase 3

Contacts and Locations

Study Locations

• Norway
  • Ostfold
    • Fredrikstad, Ostfold, Norway, 1606
      • Ostfold Hospital Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 95 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Consecutive outpatients referred to ER because of suspected DVT
• 18 years of age
• Signed informed consent

Exclusion Criteria:

1- refuse to consent

Patients with the criteria below will not be eligible for scheduled work-up:

1. Duration of the diagnostic work-up is expected to last < 2 hours
2. Presence of active cancer or receiving chemotherapy for cancer
3. Suspicion of coexisting clinical PE
4. Suspicion of active bleeding (gastrointestinal bleeding or muscle hematoma)
5. Signs of threatened circulation or having intractable pain in the lower extremity or may be considered as candidate for thrombolytic treatment
6. Physician does not consider it safe to discharge the patient
7. Presence of logistic factors that may hinder a scheduled work-up
8. Presence of co-morbid conditions that require hospital admission
9. Patient prefers not to be discharged before diagnosis is completed
10. Glomerular Filtration Rate < 45 ml/min

11. Presence of contraindications to rivaroxaban including;

    • Lesion or condition, if considered to be a significant risk for major bleeding e.g current or recent gastrointestinal ulceration, presence of malignant neoplasms at high risk of bleeding, recent brain or spinal injury, recent brain, spinal or ophthalmic surgery, recent intracranial haemorrhage, known or suspected oesophageal varices, arteriovenous malformations, vascular aneurysms or major intraspinal or intracerebral vascular abnormalities
    • Concomitant treatment with any other anticoagulants e.g. unfractionated heparin (UFH), low molecular weight heparins (enoxaparin, dalteparin, etc.), heparin derivatives (fondaparinux, etc.), oral anticoagulants (warfarin, dabigatran etexilate, apixaban etc.)
    • Hepatic disease associated with coagulopathy and clinically relevant bleeding risk including cirrhotic patients with Child Pugh B and C.
    • Pregnancy/positive pregnancy test and breastfeeding (see section 4.6)

11. Hb < 11 g/dl 12. Presence of drug interaction with rivaroxaban including concomitant systemic treatment with azole-antimycotics (such as ketoconazole, itraconazole, voriconazole and posaconazole) or HIV protease inhibitors (e.g. ritonavir), acetylsalicylic acid at a dose higher than 160 mg or platelet aggregation inhibitors

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Rivaroxaban; Rivaroxaban 15 mg every 12 hours until the completion of the diagnostic work-up, which should not exceed 24 hours.	Drug: Rivaroxaban; Rivaroxaban 15 mg every 12 hours until the completion of the diagnostic work-up, which should not exceed 24 hours (maximum 2 tablets); Other Names: Xarelto

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of serious bleedings and/or death related to bleeding	Serious bleedings and/or death related to bleeding encountered within 48 hours after the last rivaroxaban tablet was ingested in patients in whom DVT was excluded or until the ingestion of first tablet of oral anticoagulation or application of IV/SC heparin in those in whom DVT is confirmed.	Until 48 hours after last tablet

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasability rate	Assessed by the proportion of patients who can be managed by a scheduled work-up	12 hours
Failure rate	Worsening in pre-existing complaints or developement of signs/symptoms of pulmonary embolism	until 48 hours after last tablet
90-day outcome	The 90-day outcome of the applied diagnostic strategy using Wells pre-test clinical probability, D-dimer and compression ultrasounography and safety of coagulation	90 days

Collaborators and Investigators

• Sponsor: Ostfold Hospital Trust
• Investigators: Study Director: Waleed Ghanima, PhD, Ostfold Hospital Trust; Principal Investigator: Nezar Raouf, Ostfold Hopital Trust; Principal Investigator: Kristin Utne, Ostfold Hospital Trust

Publications and helpful links

General Publications

• Fronas SG, Jorgensen CT, Dahm AEA, Wik HS, Gleditsch J, Raouf N, Holst R, Klok FA, Ghanima W. Safety of a strategy combining D-dimer testing and whole-leg ultrasonography to rule out deep vein thrombosis. Blood Adv. 2020 Oct 27;4(20):5002-5010. doi: 10.1182/bloodadvances.2020002173.
• Fronas SG, Dahm AEA, Wik HS, Jorgensen CT, Gleditsch J, Raouf N, Holst R, Klok FA, Ghanima W. Safety and feasibility of rivaroxaban in deferred workup of patients with suspected deep vein thrombosis. Blood Adv. 2020 Jun 9;4(11):2468-2476. doi: 10.1182/bloodadvances.2020001556.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2015
• Primary Completion (Actual): November 30, 2018
• Study Completion (Actual): December 30, 2018

Study Registration Dates

• First Submitted: February 25, 2015
• First Submitted That Met QC Criteria: June 30, 2015
• First Posted (Estimate): July 1, 2015

Study Record Updates

• Last Update Posted (Actual): January 23, 2019
• Last Update Submitted That Met QC Criteria: January 18, 2019
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Keywords: Rivaroxaban; Deep venous thrombosis
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Embolism and Thrombosis; Thrombosis; Venous Thrombosis; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Rivaroxaban
• Other Study ID Numbers: 3304

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: There is no plan to share IPD