You know a vanguard study has been very successful when one of its key objectives – assessing recruitment potential – exceeds the number of participants reached in previous full-scale trials on the same subject!
That’s been the experience of PHRI’s study on low INR to minimize bleeding with mechanical valves (LIMIT), co-led by PHRI Investigator Emilie Belley-Côté and PHRI Scientist Richard Whitlock.
Their randomized, open-label, blinded end-point, multicenter trial, LIMIT, currently sits just over 400 participants recruited in four countries (the table shown below is from the end of May).
That exceeds the number of participants in each earlier trial on the same subject: PROACT (2018, JACC); and LOWERING-IT (2010 AHJ). Those trials also asked what is the optimal international normalized ratio (INR) value for anticoagulant therapy after mechanical mitral valve replacement – which is recommended for young adults with severe valvular disease.
Belley-Côté and Whitlock say in their trial backgrounder (see PDF) that the target INR in current guidelines “is based on low-quality observational evidence,” and that “the results of several recent RCTs suggest that lower INR targets for mechanical valves in the aortic position may decrease the risk of bleeding… and lower INR targets have similar thromboembolic risks. Therefore, the optimal INR target remains unclear.”
The LIMIT Vanguard trial determines if PHRI conducts a multi-centre RCT – of up to 2660 adult patients (18 and older) with an aortic mechanical valve – seeking to see if a low INR target (INR 1.5-2.5) is superior to target the INR in the range recommended by current guidelines with respect to major bleeding (primary outcome).
Congratulations on a strong effort by the whole LIMIT team in Hamilton, including: Kevin Kim (Project Officer); Jessica Vincent (Program Director); Kate Brady (Senior Research Coordinator); Jenny Swanson (Junior Research Coordinator); Myranda Rocha and Rachel Hensen (Research Assistants); Chinthanie Ramasundarahettige and Robin Zhao (Statisticians); Cissy Tang and Xiumei Yang (Biometrics); and Tracy Boland (Data Operations).
And of course, a huge shout out to our LIMIT study collaborators in Belgium, Russian Federation, and Spain who are also superstars in taking it [patient recruitment] to the LIMIT.