PENTHIFRA Plus Study Details

ARIXTRA for extended prophylaxis of VTE in hip fracture surgery [11]

PENTHIFRA Plus was a double-blind multicenter trial in which 656 patients undergoing hip fracture surgery were randomly assigned to receive prophylaxis with once-daily SC injection of either 2.5 mg of ARIXTRA or placebo for 19 to 23 days. Prior to randomization, all patients had received ARIXTRA for 6 to 8 days.

The primary efficacy outcome was DVT detected by mandatory bilateral venography or documented symptomatic DVT or PE during the double-blind period. The main safety outcome was major bleeding.

The incidence of DVT for treatment with ARIXTRA was 1.4% (3/208) vs 35.0% (77/220) for placebo, with a relative risk reduction of 95.9% (95% CI, 87.2-99.7; P<0.001). The rate of symptomatic VTE was reduced to 0.3% (1/326) for ARIXTRA, vs 2.7% (9/330) for placebo (P=0.21). This was a relative risk reduction of 88.8% (P=0.02).

Major bleeding occurred in 2.4% (8/327) of patients in the group treated with ARIXTRA and 0.6% (2/329) of those receiving placebo. There was a trend toward major bleeding in the group treated with ARIXTRA vs the placebo group (P=0.06); there were no differences between the 2 groups in the incidence of clinically relevant bleeding (leading to death, reoperation, or critical organ bleeding).

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.