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
Authors: Field Thalia S. , Dizonno Vanessa , Almekhlafi Mohammed A. , Bala Fouzi , Alhabli Ibrahim , Wong Hubert , Norena Monica , Villaluna Maria Karina , King-Azote Princess , Ratnaweera Namali , Mancini Steven , Van Gaal Stephen C. , Wilson Laura K. , Graham Brett R. , Sposato Luciano A. , Blacquiere Dylan , Dewar Brian M. , Boulos Mark I. , Buck Brian H. , Odier Celine , Perera Kanjana S. , Pikula Aleksandra , Tkach Aleksander , Medvedev George , Canfield Carolyn , Mortenson W. Ben , Nadeau Janel O. , Alshimemeri Sohaila , Benavente Oscar R. , Demchuk Andrew M. , Dowlatshahi Dar , Lanthier Sylvain , Lee Agnes Y.Y. , Mandzia Jennifer , Suryanarayan Deepa , Weitz Jeffrey I. , Hill Michael D. , Hill Michael , Villaluna Murray Karina , Jones Andrea , Matsubara Lauren , O’Neill Zoe , Park Sarah , Yuan Michelle , Saluzzi Marina , Dueck Ashley , McKibben K. Ingrid , Zhang Qiao , Benavente (chair) Oscar , Butcher (chair) Ken , Bushnell Cheryl , de Sousa Diana Aguiar , Hill Michael , Benavente Oscar , Wilson Dr Laura , Benavente Oscar , Lloret Mar , Lau Hsien Lee , Maclean Genoveva , Mann Sharanpal , Murphy Colleen , Smith Jonathan , Teal Philip , Tse Ming Yin (Dominic) , Yip Samuel , Naidoo VIshaya , Brar Jaskiran , Chen Shuo , Horton Myles , Hill Michael , Save Supriya , Althubait Shorog , Bogiatzi Chrysi , Boyko Matthew , Chatuverdi Surbhi , Coutts Shelagh , Ganesh Aravind , Ghavami Kimia , Harrison Emme , Hu Sherry , Jambula Anitha , Joundi Raed , Kenney Carol , Klein Gary , Lin Katie , Mansoor Salman , Marko Martha , Ryckborst Karla , Sage Kayla , Singh Nishita , Tse Ming Yin (Dominic) , Wadhwa Ankur , Wasiliw Sanchea , Graham Brett , Bhavsar Shrijal , Bold Kala , Maley Sharleen , Urroz Lilian , Foster Kaitlyn , Junk Emily , Corley Scott , Gardner Aaron , McMullen Jennifer , Whelan Ruth , Duff Whitney , Tyson Cassandra , Cooley Regan , Hunter Gary , Magee Fergall , Wasyliw Sanchea , Beauchamp Meribeth-Ann (Beth) , Lambourn Lindsay , Ayan Diana , Khaw Aleksander , Mai Lauren , Bullrich Maria Bres , Fridman Sebastian , Daham Zeinab , Fahad Robert , Shamy Michel , Stotts Grant , Fatadawala Idris , Lopes Kaitlyn , Southwell Alisia , Bhandari Vinaya , Fitzpatrick Tess , Gladstone David , Hopyan Julia , Kamra Maneesha , Khosravani Houman , Liddy Anne-Marie , Liu Zhongyu , Popel Najla , Sivakumar Keith , Swartz Richard , Yu Amy , Fairall Paige , Ahmed Farhat , Jabs Juline , White Leah , Piquette Lori , Shepherd Rekha , Ishaque Noman , Odier Céline , Simon Nandy-Shelwine , Lapierre Marlene , Bereznyakova Olena , Caporuscio Casey Boudreau , Cauchon Francois , Côté Valerie , Denault Nicole , Desciantre Yan , Gauthier Lyne , Gioia Laura , Jaquin Grégory , Jadil Nadia , Lim Sothun , Poppe Alexandra , Rodriguez Caludia , Rodriguez Marie-Christine , Stapf Christian , Vandervelde Cheyenne , Ng Kuan Huei (Kelvin) , Oczkowski Wes , Lourenco Diane , Moreau Cathay , Jolie Amber , Bhagraith Vinai , Katsanos Aristeidis , de Sa Boasquevisque Danielle , Ratnayake Kanchana , McLelland Marie , Adderly Coleen , Elamin Elsadig , Galloway Camille , Smith Michelle , Topor Tess , Singh Shobha , To William , Akthar Farhana , Casaubon Leanne , Cayley Anne , Crelling Lisa , Del Campo Martin , Gao Mingyang , Hanna Cresti , Khalid Muhammad , Pham Nga , Schaafsma Joanna , Silver Frank , Stewart TIm , Tiopanas Patricia , Wigner Rely , Williams Janice 
Published: September 2023

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.