PEGASUS Study Details

ARIXTRA for prophylaxis in abdominal surgery, including patients with cancer [12]

PEGASUS was a randomized, double-blind, double-dummy trial of abdominal surgery patients at risk for thromboembolic complications. Patients received either SC once-daily injections of ARIXTRA 2.5 mg or dalteparin sodium 5,000 IU once-daily, with one 2,500 IU SC preoperative injection and one 2,500 IU SC first postoperative injection. ARIXTRA was administered 6 hours after surgery.

Surgery was considered high risk if patients were >60 years, or >40 and <60 years with 1 or more additional risk factors for VTE, or were undergoing abdominal surgery with general anesthesia expected to last >45 minutes.

The primary efficacy outcome was DVT detected by mandatory bilateral venography, documented symptomatic DVT, or documented symptomatic PE up to Day 10. The main safety outcome measure was major bleeding during treatment.

The incidence of DVT/PE was 4.6% (47/1,027) for the group treated with ARIXTRA vs 6.1% (62/1,021) for the dalteparin group. The relative reduction in risk was 24.6% (95% CI, -9.0 to 47.9; P=0.144), which met the predetermined criterion for noninferiority of ARIXTRA. Major bleeding was observed in 3.4% (49/1,433) of patients who received ARIXTRA and 2.4% (34/1,425) of patients who received dalteparin (P=0.122). A separate analysis of major bleeding according to time of first postoperative dose of ARIXTRA after surgical closure was conducted. When ARIXTRA was dosed <6 hours after surgery, the rate of bleeding was 3.4% (9/263). However, when ARIXTRA was dosed at least 6 hours after surgery, the incidence of bleeding was 2.8% (32/1,139).

WARNING: SPINAL/EPIDURAL HEMATOMAS

Epidural or spinal hematomas may occur in patients who are anticoagulated with low molecular weight heparins (LMWH), heparinoids, or fondaparinux sodium and are receiving neuraxial anesthesia or undergoing spinal puncture.

These hematomas may result in long-term or permanent paralysis. Consider these risks when scheduling patients for spinal procedures. Factors that can increase the risk of developing epidural or spinal hematomas in these patients include:

• use of indwelling epidural catheters
• concomitant use of other drugs that affect hemostasis, such as nonsteroidal anti-inflammatory drugs (NSAIDs), platelet inhibitors, or other anticoagulants
• a history of traumatic or repeated epidural or spinal puncture
• a history of spinal deformity or spinal surgery

Monitor patients frequently for signs and symptoms of neurologic impairment. If neurologic compromise is noted, urgent treatment is necessary. Consider the benefit and risks before neuraxial intervention in patients anticoagulated or to be anticoagulated for thromboprophylaxis.

INDICATIONS AND USAGE
Prophylaxis of Deep Vein Thrombosis
ARIXTRA is indicated for the prophylaxis of deep vein thrombosis (DVT), which may lead to pulmonary embolism (PE) in patients undergoing:

• hip fracture surgery, including extended prophylaxis;
• hip replacement surgery;
• knee replacement surgery;
• abdominal surgery who are at risk for thromboembolic complications.

Treatment of Acute Deep Vein Thrombosis
ARIXTRA is indicated for the treatment of acute deep vein thrombosis when administered in conjunction with warfarin sodium.

Treatment of Acute Pulmonary Embolism
ARIXTRA is indicated for the treatment of acute pulmonary embolism when administered in conjunction with warfarin sodium when initial therapy is administered in the hospital.

CONTRAINDICATIONS
ARIXTRA is contraindicated in the following conditions:

• Severe renal impairment (creatinine clearance <30 mL/min) in prophylaxis or treatment of venous thromboembolism.
• Active major bleeding.
• Bacterial endocarditis.
• Thrombocytopenia associated with a positive in vitro test for anti-platelet antibody in the presence of fondaparinux sodium.
• Body weight <50 kg (venous thromboembolism prophylaxis only).

WARNINGS AND PRECAUTIONS

• Use with caution in patients who have conditions or who are taking concomitant medications that increase risk of hemorrhage.
• Bleeding risk is increased in renal impairment and in patients with low body weight <50 kg.
• Thrombocytopenia can occur with administration of ARIXTRA.
• Periodic routine complete blood counts (including platelet counts), serum creatinine level, and stool occult blood tests are recommended.
• The packaging (needle guard) contains dry natural rubber and may cause allergic reactions in latex sensitive individuals.