Rivaroxaban for the Treatment of Symptomatic Isolated Distal Deep Vein Thrombosis – RIDTS Study

Background: The optimal management of patients with isolated distal deep vein thrombosis (IDDVT) is uncertain. Observational studies report similar therapeutic strategies as for patients with proximal DVT or pulmonary embolism (PE), but shorter treatment duration. We compared two different durations of treatment with rivaroxaban in patients with symptomatic IDDVT.  Methods: In a randomized, double-blind, placebo-controlled trial, patients with symptomatic IDDVT received 6 weeks of rivaroxaban at standard doses and were assigned to rivaroxaban 20 mg once daily or placebo for additional 6 weeks. Randomization was done using a computer-generated randomization list and was stratified by study center. Primary efficacy outcome was a composite of recurrent IDDVT, proximal DVT, symptomatic or fatal PE. Primary safety outcome was ISTH-defined major bleeding. We here report the results of the 6-month follow-up. Findings: Of the 402 randomized patients, 200 received rivaroxaban and 202 placebo. IDDVT was unprovoked in 41.0% and 42.6% of patients, respectively. The primary efficacy outcome occurred in 5 patients (2.5%) on rivaroxaban and 21 (10.4%) treated with placebo (p=0.001). Recurrent IDDVT occurred in 3 (1.5%) and 16 (7.9%)(p=0.002); proximal DVT or PE in 2 (1.0%) and 5 (2.5%) (p=0.45), respectively. There were 3 (0.7%) major bleeding events prior to randomization, none after randomization.  Interpretation: Rivaroxaban administered for 3 months effectively and safely reduces recurrent venous thrombosis as compared to 6 weeks of treatment during a 6-month follow up. The incidence of proximal DVT and PE was low and similar between the two groups.  Clinical Trial Registration Details: EudraCT Number: 2016-000958-36. Clinical Trial Gov identifier: NCT02722447. Funding Information: Unrestricted grant from Bayer Italy. Declaration of Interests: None to declare. Ethics Approval Statement: The study was approved by the local institutional review boards or ethics committees of all participating centers and was performed in accordance with the declaration of Helsinki (52nd WMA General Assembly, Edinburgh, Scotland, October 2000) as well as with the International Conference on Harmonisation (ICH) guidelines on Good Clinical Practise (GCP).