MAGELLAN: Acutely Ill Patients
Hospitalized acutely ill patients are a heterogeneous group representing a clinical challenge with respect to prevention of venous thromboembolism (VTE). The optimal duration of thromboprophylaxis remains a key question in this group.107, 7, 108, 109, 110, 111 Multiple factors, including the acute medical condition and immobilization, contribute to an increased, but moderate, risk of VTE in these patients.6, 114, 115, 116 Few data exist to show definitively which hospitalized acutely ill patients might benefit from extended thromboprophylaxis and what factors increase the risk of VTE and bleeding.111, 117
- The influence of co-morbid conditions on the efficacy of thromboprophylaxis remains unclear
- The risk of bleeding events, although known to be higher than in the general population, is not well characterized
- The acute medical condition is challenging to manage and it places patients at an increased risk of morbidity and mortality
MAGELLAN: oral rivaroxaban versus subcutaneous enoxaparin
MAGELLAN investigated the efficacy and safety of oral rivaroxaban compared with standard-duration subcutaneous enoxaparin and evaluated the role of extended-duration thromboprophylaxis in hospitalized acutely ill patients at risk of VTE and for whom guidelines typically recommend thromboprophylaxis.107
Objective
The objectives of MAGELLAN were two-fold:
- To determine whether oral rivaroxaban 10 mg once daily was non-inferior to subcutaneous enoxaparin 40 mg once daily (both drugs were administered for 10±4 days)
- To determine whether extended-duration oral rivaroxaban 10 mg once daily (administered for 35±4 days) was superior to subcutaneous enoxaparin 40 mg once daily (administered for 10±4 days followed by placebo)
Study design
MAGELLAN was a randomized, blinded, active comparator-controlled, multinational clinical trial in hospitalized and immobilized acutely ill medical patients. A total of 8101 patients, comprising a heterogeneous group with various acute medical conditions, were randomized to one of the following regimens:
- Rivaroxaban 10 mg once daily for 35±4 days plus subcutaneous placebo once daily for 10±4 days
- Subcutaneous enoxaparin 40 mg once daily for 10±4 days plus oral placebo once daily for 35±4 days
The patients returned for a follow-up visit at day 90.107
Endpoints
- There were two primary efficacy endpoints, at:
- Day 10 (test for non-inferiority)
- Day 35 (test for superiority)
- Both endpoints comprised the composite of:
- Asymptomatic proximal deep vein thrombosis detected by mandatory ultrasonography
- Symptomatic deep vein thrombosis (proximal or distal)
- Symptomatic non-fatal pulmonary embolism
- VTE-related death
- The principal safety outcome was a composite of major bleeding and non-major clinically relevant bleeding (observed not later than 2 days after the last intake of double-blind study medication)
- 107 - Cohen AT, Spiro TE, Büller HR et al. Extended-duration rivaroxaban thromboprophylaxis in acutely ill medical patients: MAGELLAN study protocol. J Thromb Thrombolysis 2011;31:407–416.
- 7 - Cohen AT, Tapson VF, Bergmann JF, et al; ENDORSE Investigators. Venous thromboembolism risk and prophylaxis in the acute hospital care setting (ENDORSE study): a multinational cross-sectional study. Lancet. 2008;371(9610):387-394.
- 108 - Samama MM, Cohen AT, Darmon JY et al. A comparison of enoxaparin with placebo for the prevention of venous thromboembolism in acutely ill medical patients. Prophylaxis in Medical Patients with Enoxaparin Study Group. N Engl J Med 1999;341:793–800.
- 109 - Cohen AT, Davidson BL, Gallus AS et al. Efficacy and safety of fondaparinux for the prevention of venous thromboembolism in older acute medical patients: randomised placebo controlled trial. BMJ 2006;332:325–329.
- 110 - Leizorovicz A, Cohen AT, Turpie AGG et al. Randomized, placebo-controlled trial of dalteparin for the prevention of venous thromboembolism in acutely ill medical patients. Circulation 2004;110:874–879.
- 111 - Hull RD, Schellong SM, Tapson VF et al. Extended-duration venous thromboembolism prophylaxis in acutely ill medical patients with recently reduced mobility: a randomized trial. Ann Intern Med 2010;153:8–18.
- 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.
- 114 - Heit JA, Silverstein MD, Mohr DN et al. Risk factors for deep vein thrombosis and pulmonary embolism: a population-based case-control study. Arch Intern Med 2000;160:809–815.
- 115 - Russell MW, Taylor DC, Cummins G, Huse DM. Use of managed care claims data in the risk assessment of venous thromboembolism in outpatients. Am J Manag Care 2002;8:S3–S9.
- 116 - Cohen AT, Alikhan R, Arcelus JI et al. Assessment of venous thromboembolism risk and the benefits of thromboprophylaxis in medical patients. Thromb Haemost 2005;94:750–759.
- 117 - Decousus H, Tapson VF, Bergmann JF et al. Factors at admission associated with bleeding risk in medical patients: findings from the IMPROVE investigators. Chest 2011;139:69–79.
- Thromboprophylaxis
- Preventative treatment for blood clotting.
- Venous thromboembolism
- A disease process beginning with a blood clot occurring within the venous system, including deep vein thrombosis and pulmonary embolism.
- Efficacy
- The ability of a drug to produce the desired effect.
- Subcutaneous
- Introduced beneath the skin.
- Thrombosis
- Formation of a clot inside a blood vessel.
