Study of Rivaroxaban for Cerebral Venous Thrombosis: A Randomized Controlled Feasibility Trial Comparing Anticoagulation With Rivaroxaban to Standard-of-Care in Symptomatic Cerebral Venous Thrombosis

Abstract

Background: Emerging data suggest that direct oral anticoagulants may be a suitable choice for anticoagulation for cerebral venous thrombosis (CVT). However, conducting high-quality trials in CVT is challenging as it is a rare disease with low rates of adverse outcomes such as major bleeding and functional dependence. To facilitate the design of future CVT trials, SECRET (Study of Rivaroxaban for Cerebral Venous Thrombosis) assessed (1) the feasibility of recruitment, (2) the safety of rivaroxaban compared with standard-of-care anticoagulation, and (3) patient-centered functional outcomes. Methods: This was a phase II, prospective, open-label blinded-end point 1:1 randomized trial conducted at 12 Canadian centers. Participants were aged ≥18 years, within 14 days of a new diagnosis of symptomatic CVT, and suitable for oral anticoagulation; they were randomized to receive rivaroxaban 20 mg daily, or standard-of-care anticoagulation (warfarin, target international normalized ratio, 2.0–3.0, or low-molecular-weight heparin) for 180 days, with optional extension up to 365 days. Primary outcomes were annual rate of recruitment (feasibility); and a composite of symptomatic intracranial hemorrhage, major extracranial hemorrhage, or mortality at 180 days (safety). Secondary outcomes included recurrent venous thromboembolism, recanalization, clinically relevant nonmajor bleeding, and functional and patient-reported outcomes (modified Rankin Scale, quality of life, headache, mood, fatigue, and cognition) at days 180 and 365. Results: Fifty-five participants were randomized. The rate of recruitment was 21.3 participants/year; 57% of eligible candidates consented. Median age was 48.0 years (interquartile range, 38.5–73.2); 66% were female. There was 1 primary event (symptomatic intracranial hemorrhage), 2 clinically relevant nonmajor bleeding events, and 1 recurrent CVT by day 180, all in the rivaroxaban group. All participants in both arms had at least partial recanalization by day 180. At enrollment, both groups on average reported reduced quality of life, low mood, fatigue, and headache with impaired cognitive performance. All metrics improved markedly by day 180. Conclusions: Recruitment targets were reached, but many eligible participants declined randomization. There were numerically more bleeding events in patients taking rivaroxaban compared with control, but rates of bleeding and recurrent venous thromboembolism were low overall and in keeping with previous studies. Participants had symptoms affecting their well-being at enrollment but improved over time. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03178864.

Aktuelles zu Inzidenz, Risikofaktoren und Behandlung von venösen Thrombosen an ungewöhnlichen Stellen

“…Conversely, most recent data from the SECRET Trial (2023) [33], a phase 2 feasibility trial comparing rivaroxaban to standard-of-care (VKAs) in symptomatic CVT, reported numerically more bleeding events at 180 days in patients taking rivaroxaban, although rates of bleeding events and recurrent VTE were low overall and in keeping with previous evidence [33].…”

“…Im Gegensatz dazu berichteten die neuesten Daten aus der SECRET-Studie (2023) [33], einer Phase-II-Machbarkeitsstudie, in der Rivaroxaban mit Standardtherapien (VKAs) bei symptomatischen CVT verglichen wurde, nach 180 Tagen von erhöhten Blutungen bei Patienten, die Rivaroxaban einnahmen. Und dies, obwohl die Raten der Blutungsereignisse und rezidiven VTE insgesamt niedrig waren und früheren Erkenntnissen entsprachen [33].…”

Diagnosis and Management of Cerebral Venous Thrombosis: A Scientific Statement From the American Heart Association

“…[22][23][24] A prospective cohort from a Canadian randomized trial found that although 72% of individuals with CVT remained functionally independent at the time of their presentation, there was an overall substantial burden of headache, fatigue, low mood, and impaired cognitive performance. 25 A retrospective study from China including 303 patients with CVT who were employed or students before their index event found that 42% had not returned to work or school at 6 months, despite 87% reaching functional independence at the time of assessment. 26 Epilepsy may affect >10% of individuals with CVT, with risk factors including seizures at the time of onset, decreased level of consciousness or focal deficits, Prevalence of sinus involvement in CVT.…”

“…SECRET (Study of Rivaroxaban in Cerebral Venous Thrombosis) was a phase II trial that randomized 53 participants with CVT 1:1 to rivaroxaban 20 mg daily versus standard-of-care anticoagulation (warfarin; target international normalized ratio, 2.0-3.0] or LMWH) for a minimum of 6 months. 25 There was no requirement for lead-in parenteral anticoagulation. The trial excluded individuals with pregnancy and antiphospholipid antibody syndrome.…”

Efficacy and Safety of Direct Oral Anticoagulants in Cerebral Venous Thrombosis: Meta-Analysis of Randomized Clinical Trials

“…However, the efficacy and safety of DOACs in patients with CVT remains unclear. Considering these, recent randomized clinical trials (RCTs) such as RE-SPECT CVT (Safety and Efficacy of Dabigatran Etexilate Versus Dose-Adjusted Warfarin in Patients With CVT) 16 and SECRET (Study of Rivaroxaban for Cerebral Venous Thrombosis) 17 have examined the use of DOACs compared with standard of care in patients with CVT. Therefore, we performed a systematic review and meta-analysis of clinical trials to evaluate the efficacy and safety outcomes of DOACs when compared with the current standard of care in adult patients with CVT.…”