TORONTO, Dec. 7, 2016 -- St. Joseph's Research, Hamilton and LEO Pharma Inc. have announced positive findings from the TRIVET (Tinzaparin in Renal Insufficiency Venous Thromboembolism) Study. The study assessed tinzaparin accumulation, defined as trough anti-Xa levels >0.5 IU/mL, when administered at the full therapeutic dose in patients with VTE and varying degrees of renal impairment. Patients were stratified into four groups reflecting Cockcroft-Gault creatinine clearance (CrCl): >60 mL/min (normal renal function), 30–60 mL/min, ≤30 mL/min and dialysis dependent.
The mean trough anti-Xa levels remained well below the 0.5 IU/mL threshold in all four groups, including dialysis-dependent patients, indicating no clinically significant accumulation with tinzaparin when used at the full dose (175 IU/kg).
Additionally, although individual patients in all four groups experienced anti-Xa levels >0.5 IU/mL, these did not correlate with bleeding events. All bleeding events (18/148) occurred in patients with anti-Xa <0.5 IU/mL, with the exception of one patient with minor bleeding who had anti-Xa >0.5 IU/mL at the time of the event. Major bleeding occurred in 1/38, 1/29, and 1/25 patients in the CrCl 30–60 mL/min, CrCl ≤30 mL/min, and dialysis-dependent groups, respectively.
St. Joseph's research investigator, Dr. Mark Crowther who co-authored the study with fellow investigators, Dr. Wendy Lim and Dr. Christine Ribic said, "The TRIVET study provides the most robust data for tinzaparin in patients with severe renal impairment, without dose adjustment." Adding to this observation, Dr. Ribic commented, "These findings confirm our clinical experience with tinzaparin in this patient population."
The effect of renal impairment on bioaccumulation of LMWH has not been fully studied. The TRIVET study adds to the data available for tinzaparin in patients with severe renal impairment. The safety and efficacy of anticoagulation in patients with severe renal impairment is an area that remains under investigation.
About Venous Thromboembolism
Venous thromboembolism (VTE) is a disease that encompasses two serious conditions: deep vein thrombosis (DVT), in which a blood clot forms in a deep vein, often in the leg, and pulmonary embolism (PE), in which a blood clot breaks loose and travels to the lungs. Risk factors for VTE include lifestyle factors, cancer, pregnancy and surgery. Additionally, advancing age is a risk factor for both VTE and renal insufficiency. By age 70, renal function is decreased by approximately 40%. These facts underscore the importance of the TRIVET Study findings.
About the TRIVET Study
The TRIVET Study was a prospective multicentre cohort study in 148 patients with objectively confirmed VTE treated with tinzaparin at the full dose (175 IU/kg). Trough anti-Xa levels were measured twice: day 3–5 of treatment and again on day 5–7 of treatment. TRIVET is the first and largest LMWH study to address the question of bioaccumulation in patients with severe renal impairment and was entirely conducted in Canadian centres by Canadian investigators.
About innohep (tinzaparin)
innohep (tinzaparin) is a low molecular weight heparin (LMWH) used for the prevention and treatment of VTE, as well as the prevention of clotting in indwelling intravenous lines for hemodialysis. Tinzaparin has a greater mean molecular weight and negative charge compared to other LMWHs and may be less likely to accumulate in patients with impaired kidney function.1-3footnotes 1, 2 and 3
About LEO Pharma A/S
LEO Pharma is a global healthcare company that offers care solutions within dermatology and thrombosis to patients in more than 100 countries around the world. Founded in 1908 and owned by the LEO Foundation, LEO Pharma has devoted decades of research and development to delivering products and solutions to people with skin conditions and thrombosis. LEO Pharma is headquartered in Denmark and employs around 5,000 people worldwide.
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- Nagge J, Crowther M, Hirsh J., Is impaired renal function a contraindication to the use of low-molecular-weight heparin? Arch Intern Med. 2002;162(22):2605-9.
- Johansen KB, Balchen T. Tinzaparin and other low-molecular-weight heparins: what is the evidence for differential dependence on renal clearance? Experimental hematology & oncology. 2013;2(1):21.
- Crowther MA, Berry LR, Monagle PT, Chan AK. Mechanisms responsible for the failure of protamine to inactivate low-molecular-weight heparin. Br J Haematol. 2002;116(1):178-86.