RECORD Programme: 4 Completed Phase III Studies on Total Knee and Total Hip Replacement Surgery

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

The RECORD (REgulation of Coagulation in ORthopaedic Surgery to Prevent Deep Vein Thrombosis Thrombosis
Formation of a clot inside a blood vessel.
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)1,2,3,4

  • In the RECORD1 study, extended regimens of oral, once-daily rivaroxaban 10 mg and a once-daily injection of enoxaparin in a 40 mg dose were compared for the prevention of VTE VTE
    Venous thromboembolism (= VTE). A disease process beginning with a blood clot occurring within the venous system, including deep vein thrombosis and pulmonary embolism.
    in patients undergoing elective total hip replacement. Rivaroxaban was initiated 6–8 hours after wound closure and continued for 31–39 days. Enoxaparin was initiated 12 hours before surgery, restarted 6–8 hours after surgery and then continued for 31–39 days.
     
  • In the RECORD2 study, to investigate the benefits of an extended treatment regimen in the prevention of VTE in patients undergoing elective total hip replacement, oral, once-daily rivaroxaban 10 mg was initiated 6–8 hours after wound closure and continued for 31–39 days. This was compared with a short-term regimen of a once-daily injection of enoxaparin in a 40 mg dose. Enoxaparin was given 12 hours before surgery, restarted 6–8 hours after surgery, continued for 10–14 days, and followed by placebo up to 31–39 days.
     
  • In the RECORD3 study, oral, once-daily rivaroxaban 10 mg was compared with a once-daily injection of enoxaparin in a 40 mg dose for the prevention of VTE in patients undergoing elective total knee replacement. Rivaroxaban was initiated 6–8 hours after wound closure. Enoxaparin was initiated 12 hours before surgery and given again 6–8 hours after wound closure. Both study medications were continued at least to day 10 and up to day 14.
     
  • In the RECORD4 study, a short-term treatment regimen with oral, once-daily rivaroxaban 10 mg was compared with a twice-daily injection of enoxaparin 30 mg (approved US dosing) in the prevention of VTE in patients undergoing elective total knee replacement. Rivaroxaban was initiated 6–8 hours after wound closure and enoxaparin was initiated 12–24 hours after wound closure. Both study medications were continued at least to day 10 and up to day 14.

Background

  • Venous thromboembolism (VTE), which encompasses both deep vein thrombosis thrombosis
    Formation of a clot inside a blood vessel.
    (DVT DVT
    Deep vein thrombosis (= DVT). A blood clot in a deep vein, usually resulting from damage to the vein or blood flow slowing down or stopping. Usually DVTs are found in the leg, but can also be in the arm. Distal DVTs are found in deep veins of the calf, and are the most common type of DVT. Proximal DVTs are found in the legs above the calf muscle up to the waist.
    ) and pulmonary embolism (PE PE
    Pulmonary embolism (= PE). A potentially fatal condition caused by a blood clot blocking a vessel in the lung: usually the clot originates from a DVT in the legs. PE can result in permanent lung damage.
    ), is one of the most frequently occurring serious complications after elective hip or knee replacement surgery
     
  • Approximately 40–85% of orthopaedic surgery patients are thought to be at risk of VTE if appropriate thromboprophylaxis thromboprophylaxis
    Preventative treatment for blood clotting.
    is not administered,
     
  • Guidelines recommend VTE prophylaxis after major orthopaedic surgery major orthopaedic surgery
    Major operations on the bones or joints including total hip or knee replacement surgery.
    with low molecular weight heparins (LMWH LMWH
    Low molecular weight heparin (= LMWH). An anticoagulant used to prevent new clots forming and existing clots from getting larger. It is injected subcutaneously.
    ), fondaparinux or vitamin K antagonists (VKA VKA
    Vitamin K antagonist (= VKA). An anticoagulant that inhibits multiple steps in the blood clotting process. Administered orally, the dose varies by patient, and regular monitoring and dose adjustment are required. Vitamin K antagonists have interactions with food and other drugs. Due to the many limitations of this drug, many of those who are treated are outside of the required target INR range, which can be the cause for increased bleeding or a greater risk of stroke.
    ), 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 anticoagulant
    Anticoagulant drugs are used to treat and prevent blood clots. Sometimes referred to as ‘blood thinners’.
    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 subcutaneous
Introduced beneath the skin.
enoxaparin for the prevention of VTE after THR or TKR surgery in adult patients.1,2,3,4

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.

The RECORD Programme: RECORD1, 2, 3 and 4 Trials about Background, Study Design and Endpoints

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