Clinical trial NCT02486445: Rivaroxaban for Scheduled Work-up of DVT - The Ri-Schedule Study
Official title: Rivaroxaban for Scheduled Work-up of Patients With Suspected Deep Venous Thrombosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Deep Venous Thrombosis
Keywords: Deep venous thrombosis
Rivaroxaban
Lead sponsor: Ostfold Hospital Trust
Sponsor class: OTHER
First posted: 2015-07-01
Enrollment: 625
Sex: ALL
Minimum age (years): 18
Maximum age (years): 95
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

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.

Eligibility criteria: 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

Primary outcomes:
measure: Rate of serious bleedings and/or death related to bleeding
timeFrame: Until 48 hours after last tablet
Secondary outcomes:
measure: Feasability rate
timeFrame: 12 hours
measure: Failure rate
timeFrame: until 48 hours after last tablet
measure: 90-day outcome
timeFrame: 90 days
Other outcomes:
Locations:
city: Fredrikstad
country: Norway
facility: Ostfold Hospital Trust
state: Ostfold
Study officials:
affiliation: Ostfold Hospital Trust
name: Waleed Ghanima, PhD
role: STUDY_DIRECTOR
affiliation: Ostfold Hopital Trust
name: Nezar Raouf
role: PRINCIPAL_INVESTIGATOR
affiliation: Ostfold Hospital Trust
name: Kristin Utne
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.