The RECORD Programme: RECORD1, 2, 3 and 4 Trials

The RECORD (REgulation of Coagulation in ORthopaedic Surgery to Prevent Deep Vein Thrombosis and Pulmonary Embolism) programme comprised four randomized clinical trials of rivaroxaban for the prevention of venous thromboembolism in adult patients after total hip replacement (THR) or total knee replacement (TKR)2, 3, 4, 69
  • RECORD1: oral rivaroxaban (10 mg once daily [od]) started 6–8 hours after surgery versus subcutaneous enoxaparin (40 mg od) started 12–24 hours after surgery for 31–39 days in patients undergoing THR2
  • RECORD2: oral rivaroxaban (10 mg od) started 6–8 hours after surgery for 31–39 days versus subcutaneous enoxaparin (40 mg od) started 12–24 hours after surgery for 10–14 days (followed by placebo) in patients undergoing THR3
  • RECORD3: oral rivaroxaban (10 mg od) started 6–8 hours after surgery versus subcutaneous enoxaparin (40 mg od) started 12 hours before surgery for 10–14 days in patients undergoing TKR4
  • RECORD4: oral rivaroxaban (10 mg od) started 6–8 hours after surgery versus subcutaneous enoxaparin (30 mg od) started 12–24 hours after surgery for 10–14 days in patients undergoing TKR69

Background

  • Venous thromboembolism (VTE), which encompasses both deep vein thrombosis (DVT) and pulmonary embolism (PE), is one of the most frequently occurring serious complications after elective hip or knee replacement surgery59
  • Approximately 40–85% of orthopaedic surgery patients are thought to be at risk of VTE if appropriate thromboprophylaxis is not administered59, 6
  • Guidelines recommend VTE prophylaxis after major orthopaedic surgery with low molecular weight heparins (LMWH), fondaparinux or vitamin K antagonists (VKA), but these traditional anticoagulants have limitations:
    • Parenteral administration: LMWH, fondaparinux
    • Routine coagulation monitoring: LMWH, VKAs
    • Multiple food and drug interactions: VKAs
  • With a trend towards shorter hospital stays and thromboprophylaxis recommended for up to 35 days after THR and at least 10 days after TKR, a simple, effective, oral anticoagulant would be beneficial, especially in the outpatient setting

Objective of the RECORD programme

The RECORD programme compared the efficacy and safety of oral rivaroxaban with subcutaneous enoxaparin for the prevention of VTE after THR or TKR surgery in adult patients.2, 3, 4, 69

Study design

The RECORD programme comprised four randomized, double-blinded, active comparator-controlled, multinational phase III clinical trials in patients scheduled to undergo elective THR or TKR surgery. More than 12,500 patients from 39 countries were randomly assigned to one of regimens detailed below in Table 1.


Number of patients in RECORD 1,2,3 and 4 trials
 

Endpoints

The endpoints were the same for all four RECORD studies:
  • The primary efficacy endpoint was total VTE defined as the composite of deep vein thrombosis, non-fatal pulmonary embolism and death from any cause
  • The primary safety outcome was the incidence of major bleeding

Study Results >
  • 2 - Eriksson BI, Borris LC, Friedman RJ, et al; RECORD1 Study Group. Rivaroxaban versus enoxaparin for thromboprophylaxis after hip arthroplasty. N Engl J Med. 2008;358(26):2765-2775.
  • 3 - Kakkar AK, Brenner B, Dahl OE, et al; RECORD2 Investigators. Extended duration rivaroxaban versus short-term enoxaparin for the prevention of venous thromboembolism after total hip arthroplasty: a double-blind, randomised controlled trial. Lancet. 2008;372(9632):31-39.
  • 4 - Lassen MR, Ageno W, Borris LC, et al; RECORD3 Investigators. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty. N Engl J Med. 2008;358(26):2776-2786.
  • 69 - Turpie AGG, Lassen MR, Davidson BL, et al; RECORD4 Investigators. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty (RECORD4): a randomised trial. Lancet. 2009;373(9676):1673-1680
  • 59 - House of Commons Health Committee. The prevention of venous thromboembolism in hospitalised patients. Available at http://www.publications.parliament.uk/pa/cm200405/cmselect/cmhealth/99/99.pdf
  • 6 - Geerts WH, Bergqvist D, Pineo GF, et al. Prevention of venous thromboembolism: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008;133(6 suppl):381S-453S.
Thrombosis
Formation of a clot inside a blood vessel.
Venous thromboembolism
A disease process beginning with a blood clot occurring within the venous system, including deep vein thrombosis and pulmonary embolism.
Subcutaneous
Introduced beneath the skin.
Major orthopaedic surgery
Major operations on the bones or joints including total hip or knee replacement surgery.
Thromboprophylaxis
Preventative treatment for blood clotting.
Low molecular weight heparin
An anticoagulant used to prevent new clots forming and existing clots from getting larger. It is injected subcutaneously (under the skin).
Efficacy
The ability of a drug to produce the desired effect.

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