Summary

• MAGELLAN was a phase 3 study comparing the efficacy and safety of inpatients and extended thromboprophylaxis with XARELTO  and enoxaparin along with placebo for the prevention of venous thromboembolism (VTE) in acutely ill medical patients requiring hospitalization.^1,2
  • In a subgroup analysis of the MAGELLAN study, VTE prophylaxis with XARELTO reduced the risk of VTE but increased the bleeding rate in patients with pulmonary infections compared to enoxaparin.³

CLINICAL DATA

MAGELLAN Study

MAGELLAN was a phase 3, international, randomized, double-blind study designed to evaluate the efficacy and safety of extended thromboprophylaxis with XARELTO compared with standard-duration enoxaparin for the prevention of VTE in hospitalized acutely ill medical patients during the inpatient and postdischarge periods. Patients (N=8101) were randomized to receive either subcutaneous (SC) placebo daily for 10±4 days plus XARELTO  10 mg daily for 35±4 days or SC enoxaparin 40 mg daily for 10±4 days plus oral placebo daily for 35±4 days.

The 2 coprimary efficacy outcomes included the composite of asymptomatic proximal deep vein thrombosis (DVT) (detected by mandatory compression ultrasonography), symptomatic proximal or distal DVT, symptomatic nonfatal pulmonary embolism, and VTE-related death at day 10±4 (tested for noninferiority) and at day 35±4 (tested for superiority).^1,2 Secondary outcomes included symptomatic VTE and VTE-related death.³

The principal safety outcome was clinically relevant bleeding, defined as the composite of major bleeding and clinically relevant nonmajor bleeding events observed no later than 2 days after the last study drug was administered.^1,2

Subgroup Analysis of MAGELLAN Study

Cohoon et al (2018)³ conducted a subgroup analysis to determine the incidence of VTE, specific infection locations as risk factors for VTE, and the efficacy and safety of prophylaxis with extended-duration XARELTO  vs standard-duration enoxaparin among the patients hospitalized due to acute infectious diseases in the MAGELLAN population.

• Pulmonary infections were the most common infection type in patients (58.6%; XARELTO, n=936; enoxaparin, n=923).
• Infections were allocated by location into one of the following categories: bacteremia/sepsis; head, eyes, ear, neck, and throat (HEENT); pulmonary; gastrointestinal; genitourinary; skin/soft tissue; and other sites.
  • Pulmonary infections that were screened in this analysis included: bronchiectasis, bronchiolitis, bronchitis (bacterial or viral), bronchopneumonia, bronchitis viral, coccidioidomycosis, empyema, H1N1 influenza, infective exacerbation of chronic obstructive airways disease, influenza, legionella infection, lobar pneumonia, lower respiratory tract infection, lower respiratory tract infection-bacterial, lung abscess, lung infection, lung infection-pseudomonal, parainfluenzae virus infection, pleural infection, pneumonia (bacterial, fungal, klebsiella, legionella, pneumococcal, primary atypical, or staphylococcal), pulmonary mycosis, pulmonary tuberculosis, pyopneumothorax, respiratory tract infection (bacterial or viral), tuberculosis, and viral infection.
  • Infections caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), or 2019 novel coronavirus disease (COVID-19), were not included as a subgroup of this analysis.
• Among patients with pulmonary infections, significantly fewer primary efficacy outcomes occurred with XARELTO vs enoxaparin at days 10 and 35. Secondary outcomes also had fewer occurrences with XARELTO at day 10. See Table: Efficacy Outcomes at Day 10 and Day 35 in Patients with Pulmonary infections.

• Among patients with pulmonary infections, both the primary safety outcome and the major bleeding outcome occurred more frequently with XARELTO vs enoxaparin. Four patients receiving XARELTO had pulmonary bleeding. See Table: Safety Outcomes at Day 35 in Patients with Pulmonary Infections.

• The limitations of this subgroup analysis were its retrospective design, low power, and post hoc nature.

LITERATURE SEARCH

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, DERWENT^® (and/or other resources, including internal/external databases) was conducted on 06 January 2024.