Prospective, randomized, controlled trial assessing the effects of methylene blue for the prevention of hypotension during renal replacement therapy: protocol paper and statistical analysis plan for the BLUE study

Objective:  To describe the study protocol and statistical analysis plan that will be used to evaluate whether methylene blue reduces interventions aimed at controlling hypotension during renal replacement therapy as compared to usual care.

Methods:  BLUE is a randomized, multicenter, open-label trial. Patients with high risk of hypotension during renal replacement therapy will be randomized to receive either methylene blue infusion at a dose of 1mg/kg as a bolus, followed by continuous infusion of 0.1mg/kg of body weight in a total of 200mL of saline solution throughout the dialysis session, or to usual care. The usual care group will not receive any intervention. A total of 260 patients is expected to be randomized in a 1:1 ratio.

Results:  The primary outcome will be a composite of any of the following events: (1) initiation of vasopressor therapy or an increase of at least 20% from baseline dose; (2) interruption of the renal replacement therapy session; or (3) interruption of fluid removal at the request of the attending physician at any point during the session. Secondary outcomes include the occurrence of hypotension during the hemodialysis session, the maximum vasopressor dose within the first 24 hours, intensive care unit mortality, and in-hospital mortality.

Conclusion:  The BLUE study will provide evidence on the role of methylene blue in preventing hypotension during renal replacement therapy.

Keywords:
Methylene blue; Hypotension; Hemodialysis; Acute kidney injury; Schock; Renal replacement therapy