HESTAT: Study protocol for a phase II/III, randomized, placebo-controlled, single blind study to evaluate the new hemostatic agent TT-173 in total knee arthroplasty

Abstract

Background: Several hemostatic treatments intended to reduce the bleeding associated to total knee arthroplasty have been investigated with varying degrees of success. TT-173 is a new topical agent based on recombinant tissue factor that activates the extrinsic pathway of coagulation. This trial aim is to evaluate the efficacy and safety of TT-173 in total knee arthroplasty.

Methods/design: This is a phase II/III, sequential, simple blind, randomized, multicenter, placebo controlled and parallel clinical trial that will recruit 189 evaluable patients. Those randomized to treatment group will receive 2mg of TT-173 over the surgical surfaces of the knee. Control patients will receive physiologic saline. The follow up will consist in 6 visits during a period of 35 (±7) days. Primary endpoints will be the total blood loss and the incidence and severity of adverse events. Secondary and exploratory endpoints will include drainage production, decrease in hemoglobin level, transfusion ratio, analytical alterations, pain intensity, motion range, immunogenicity of TT-173 and the occurrence of systemic absorption. At the end of phase II, results will be evaluated by an independent committee that will recommend the continuation or the discontinuation of the trial.

Discussion: The design proposed maximizes the safety of the participants, avoids the risk of bias derived from the limitations of masking and enable the eventual discontinuation of the trial if this is recommended by the Interim Analysis Committee. If TT-173 proves its efficacy and safety in this indication, it would become a useful tool to improve the bleeding control in total knee arthroplasty.

Trial registration: ClinicalTrials.gov identifier: NCT02687399. Registered the 9th of February 2016.

Keywords: Hemostatic agent; Randomized controlled trial; TT-173; Topical; Total knee arthroplasty.