Greater Risks With Post-TAVR Rivaroxaban Halt GALILEO Trial

Patrice Wendling

October 10, 2018

The phase 3 GALILEO trial has been terminated early after a preliminary analysis showed that rivaroxaban (Xarelto; Bayer/Janssen) was associated with an increase in all-cause death, thromboembolic events, and bleeding when given following successful transcatheter aortic valve replacement (TAVR).

The trial's data safety monitoring board recommended stopping the trial in August after the analysis showed that patients treated with rivaroxaban vs an antiplatelet therapy had higher rates of the primary efficacy outcome of death or first adjudicated thromboembolic event (11.4% vs 8.8%), as well as the primary safety outcome of primary bleeding (4.2% vs 2.4%). All-cause death rates were also higher with rivaroxaban (6.8% vs 3.3%).

The results were disclosed in an October 3 "Dear Healthcare Professional" letter from Bayer, sent "in agreement with European Medicines Agency and the Health Products Regulatory Authority (HPRA)."

"These results are preliminary and based on incomplete data collection," the letter notes. "The final study data will be assessed by regulatory authorities as soon as they are available, including an assessment of any implications for approved indications."

Rivaroxaban is not approved for thromboprophylaxis in patients with prosthetic heart valves, including patients who have undergone TAVR, the letter adds, "and should not be used in such patients. Rivaroxaban treatment should be stopped in patients who undergo TAVR and switched to standard of care."

The blockbuster clot-prevention drug has been the subject of more than 20,000 lawsuits in federal and state courts alleging injuries with rivaroxaban. As reported earlier this year, a Pennsylvania state court overturned a $28 million verdict against Bayer AG and Johnson & Johnson's Janssen Pharmaceuticals unit, which jointly developed the drug.

The global GALILEO trial started in December 2015 and sought to compare a rivaroxaban-based antithrombotic strategy (rivaroxaban 10 mg once daily plus aspirin 75-100 mg once daily for the first 90 days followed by rivaroxaban alone) to an antiplatelet-based strategy (aspirin 75-100 mg once daily plus clopidogrel 75 mg once daily for the first 90 days followed by aspirin alone) after successful native or valve-in-valve TAVR.

The open-label trial had enrolled 1644 participants at 139 sites and was estimated to be completed October 22, 2018. Patients with atrial fibrillation at randomization were excluded from this trial.

Analyses are ongoing, the company adds. Healthcare professionals are asked to report any suspected adverse reactions to HPRA Pharmacovigilance ( or to Bayer.

The decision to prematurely halt GALILEO will likely affect the ongoing GALILEO-4D trial, a substudy that uses the same randomization as the main trial with the addition of a 4D CT scan and echocardiography 90 days post randomization to evaluate which strategy is superior at preventing valve leaflet thickening and reduced leaflet motion.

As previously reported, results of the MAUDE trial suggest that leaflet thrombosis after TAVR is associated with cardiogenic shock and death.

Currently approved indications for rivaroxaban outlined in the letter include the following:

  • rivaroxaban 2.5 mg, coadministered with acetylsalicylic acid (ASA) alone or with ASA plus clopidogrel or ticlopidine, for the prevention of atherothrombotic events in adult patients after an acute coronary syndrome with elevated cardiac biomarkers; and coadministered with ASA, for the prevention of atherothrombotic events in adult patients with coronary artery disease or symptomatic peripheral artery disease at high risk of ischemic events;

  • rivaroxaban 10 mg for prevention of venous thromboembolism in adult patients undergoing elective hip or knee replacement surgery;

  • the 15-mg and 20-mg doses for prevention of stroke and systemic embolism in adult patients with nonvalvular atrial fibrillation with one or more risk factors, such as congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, or prior stroke or transient ischemic attack;

  • the 10-mg, 15-mg and 20-mg doses for treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE) and for prevention of recurrent DVT and PE in adults.

GALILEO is sponsored by Bayer. GALILEO-4D is sponsored by the European Cardiovascular Research Institute.

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