Table 2:

Efficacy outcomes for pediatric VTE treatment and prevention clinical trials

VTE treatment and secondary prevention clinical trials
	2011 Definitions (13)	2022 Update	Comments regarding changes
Primary	Composite of: All recurrent VTE defined as either contiguous progression or non-contiguous new thrombus and including DVT, PE and paradoxical embolism (asymptomatic and symptomatic) VTE-related mortality	Composite of: Symptomatic, recurrent VTE and/or VTE progression	Broader definition of VTE beyond only DVT, PE, paradoxical embolism Include only symptomatic VTE in treatment/ secondary prophylaxis trials Moved VTE-related mortality to secondary outcome
Secondary	Each individual component of primary outcome All-cause mortality New symptomatic DVT (including DVT progression) New symptomatic PE New paradoxical embolism New asymptomatic DVT (including DVT progression) Post thrombotic syndrome	VTE-related mortality* All-cause mortality Clinically unsuspected VTE Symptomatic recurrent VTE, by location Site-specific post-thrombotic sequelae Thrombus resolution	Broader definition of VTE beyond only DVT, PE, paradoxical embolism Symptomatic VTE no longer secondary outcome since it is primary outcome Clinically unsuspected VTE moved to secondary outcome Broader definition of post thrombotic sequelae Addition of thrombus resolution
Primary VTE prevention clinical trials
Primary	Composite of: All incident VTE including DVT, PE and paradoxical embolism and VTE-related mortality	Composite of: All incident VTE, including both clinically unsuspected and symptomatic events	Broader definition of VTE “Asymptomatic” changed to “clinically unsuspected” Moved VTE-related mortality to secondary outcome
Secondary	Each individual component of primary outcome All-cause mortality	VTE-related mortality* All-cause mortality Clinically unsuspected VTE Symptomatic VTE	Symptomatic and clinically unsuspected VTE are separate secondary outcomes

VTE: venous thromboembolism; DVT: deep vein thrombosis; PE: pulmonary embolism

^*VTE-related mortality is challenging to define and rare. Recommend these events be summarized with relevant details in manuscripts.