Semuloparin for prevention of venous thromboembolism after major orthopedic surgery: results from three randomized clinical trials, SAVE-HIP1, SAVE-HIP2 and SAVE-KNEE

J Thromb Haemost. 2012 May;10(5):822-32. doi: 10.1111/j.1538-7836.2012.04701.x.

Abstract

Background: Semuloparin is a novel ultra-low-molecular-weight heparin under development for venous thromboembolism (VTE) prevention in patients at increased risk, such as surgical and cancer patients.

Objectives: Three Phase III studies compared semuloparin and enoxaparin after major orthopedic surgery: elective knee replacement (SAVE-KNEE), elective hip replacement (SAVE-HIP1) and hip fracture surgery (SAVE-HIP2).

Patients/methods: All studies were multinational, randomized and double-blind. Semuloparin and enoxaparin were administered for 7-10 days after surgery. Mandatory bilateral venography was to be performed between days 7 and 11. The primary efficacy endpoint was a composite of any deep vein thrombosis, non-fatal pulmonary embolism or all-cause death. Safety outcomes included major bleeding, clinically relevant non-major (CRNM) bleeding, and any clinically relevant bleeding (major bleeding plus CRNM).

Results: In total, 1150, 2326 and 1003 patients were randomized in SAVE-KNEE, SAVE-HIP1 and SAVE-HIP2, respectively. In all studies, the incidences of the primary efficacy endpoint were numerically lower in the semuloparin group vs. the enoxaparin group, but the difference was statistically significant only in SAVE-HIP1. In SAVE-HIP1, clinically relevant bleeding and major bleeding were significantly lower in the semuloparin vs. the enoxaparin group. In SAVE-KNEE and SAVE-HIP2, clinically relevant bleeding tended to be higher in the semuloparin group, but rates of major bleeding were similar in the two groups. Other safety parameters were generally similar between treatment groups.

Conclusions: Semuloparin was superior to enoxaparin for VTE prevention after hip replacement surgery, but failed to demonstrate superiority after knee replacement surgery and hip fracture surgery. Semuloparin and enoxaparin exhibited generally similar safety profiles.

Trial registration: ClinicalTrials.gov NCT00697099 NCT00718224 NCT00721760.

Publication types

  • Clinical Trial, Phase III
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Arthroplasty, Replacement, Hip / adverse effects
  • Arthroplasty, Replacement, Knee / adverse effects
  • Double-Blind Method
  • Drug Administration Schedule
  • Enoxaparin / administration & dosage*
  • Enoxaparin / adverse effects
  • Female
  • Fibrinolytic Agents / administration & dosage*
  • Fibrinolytic Agents / adverse effects
  • Fracture Fixation / adverse effects
  • Hemorrhage / chemically induced
  • Heparin, Low-Molecular-Weight / administration & dosage*
  • Heparin, Low-Molecular-Weight / adverse effects
  • Hip Fractures / surgery
  • Humans
  • Male
  • Middle Aged
  • Odds Ratio
  • Orthopedic Procedures / adverse effects*
  • Orthopedic Procedures / mortality
  • Phlebography
  • Risk Assessment
  • Risk Factors
  • Time Factors
  • Treatment Outcome
  • Venous Thromboembolism / diagnostic imaging
  • Venous Thromboembolism / etiology
  • Venous Thromboembolism / mortality
  • Venous Thromboembolism / prevention & control*
  • Young Adult

Substances

  • Enoxaparin
  • Fibrinolytic Agents
  • Heparin, Low-Molecular-Weight
  • semuloparin

Associated data

  • ClinicalTrials.gov/NCT00697099
  • ClinicalTrials.gov/NCT00718224
  • ClinicalTrials.gov/NCT00721760