Khorana 2019.

Study characteristics
Methods	Trial acronym: CASSINI Design: double‐blind, randomised, placebo‐controlled, parallel‐group, multicentre Phase IIIB study Median follow‐up duration: not reported
Participants	High‐risk ambulatory patients with solid cancer or lymphoma who had a Khorana score of ≥ 2, had a plan to start a new systemic regimen within 1 week before or after initiating the trial regimen and had no DVT on screening ultrasonography. Enrolled patients underwent venous duplex compression ultrasonography of both legs to rule out pre‐existing proximal DVT. Median age: 63 (range 23–88) years overall; 63 (range 23–87) years in rivaroxaban group; 62 (range 28–88) years in placebo group Gender, n (%) males: 428 (50.9%) overall; 222 (52.9%) in rivaroxaban group; 206 (48.9%) in placebo group Metastatic disease: 54.5% overall in those with solid tumour Previous VTE, n (%): 15 (1.7%) overall; 13 (3.1%) in rivaroxaban group; 2 (0.5%) in placebo group
Interventions	Intervention: rivaroxaban 10 mg once daily up to day 180 Control: placebo up to day 180 Mean intervention period was 4.3 months
Outcomes	Primary efficacy endpoint: composite of objectively confirmed symptomatic or asymptomatic lower‐extremity proximal DVT, symptomatic upper extremity, symptomatic lower‐extremity distal DVT, symptomatic or incidental PE, and VTE‐related death Secondary efficacy endpoints: included components of the primary endpoint, symptomatic VTE, death from any cause, confirmed arterial thromboembolism, and confirmed visceral thromboembolism
Notes	Funding: by Janssen, Bayer, and the Sondra and Stephen Hardis Chair in Oncology Research (to Dr Khorana), by grants (U01HL143402 and R34 HL127156, to Dr Khorana) from the National Heart, Lung, and Blood Institute, and by the Cleveland Clinic Center of Excellence for Cancer‐Associated Thrombosis (to Dr Khorana) and the Porter Family Fund (to Dr Khorana). Disclosure of potential conflicts of interest: all authors reported conflicts of interest Publication format: full‐text publication
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Patients without thrombosis were randomly assigned in a 1:1 ratio to receive rivaroxaban at a dose of 10 mg or placebo orally once daily for 180 days (with a window of ±3 days) according to a computer generated randomization schedule." Comment: adequate method of sequence generation.
Allocation concealment (selection bias)	Low risk	Quote: "Patients without thrombosis were randomly assigned in a 1:1 ratio to receive rivaroxaban at a dose of 10 mg or placebo orally once daily for 180 days (with a window of ±3 days) according to a computer generated randomization schedule." Comment: adequate method of allocation concealment.
Blinding (performance bias and detection bias) All outcomes	Low risk	Quote: "… as adjudicated by an independent clinical end‐point committee whose members were unaware of the trial‐group assignments." and "Double‐blind, randomized, placebo‐controlled." Comment: double‐blind, randomised, placebo‐controlled and all endpoints adjudicated by blinded independent committees.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Comment; all participants enrolled were analysed as reported in the methods.
Selective reporting (reporting bias)	Low risk	Comment: all outcomes reported in the methods section were addressed in the results or discussion section.