What should I keep in mind if my patient is enrolled in SAFE-SSPE?

  • The following medications are not compatible with the study medication: oral or parenteral anticoagulants, GP IIb/IIIa inhibitors, strong CYP3A4 inhibitors (HIV-protease inhibitors, systemic azole-antifungals), strong CYP3A4 inducers (rifampicin, rifabutin, phenytoin, phenobarbital, primidone, carbamazepine, St. John’s wort) or dual anti-platelet use. If these drugs are temporarily indicated, the trial medication should be paused and then restarted after discontinuation of the respective drug as soon as possible. In the event of a long-term indication for one of these drugs (e.g. anticoagulation in newly diagnosed atrial fibrillation), the study medication should be completely discontinued.
  • The use of non-steroidal anti-inflammatory drugs (NSAIDs) or monotherapy with aspirin or clopidogrel is permitted if strongly indicated. Mechanical thromboprophylaxis (e.g. compression stockings) is also permitted.
  • If a medical procedure is needed that requires the discontinuation of anticoagulation, the study medication should be paused for at least 24 hours before the procedure and restarted as soon as possible after the procedure. If medically indicated, bridging therapy with unfractionated or low molecular weight heparin can be used for the duration of the paused study medication.
  • In the event of an emergency intervention, the study medication should be paused immediately. If emergency reversal of the anticoagulation effect is necessary, unblinding should be considered. After the intervention, the trial drug should be restarted as soon as clinically possible. If necessary from a medical point of view, the pausation of the study medication can also be bridged with low molecular weight heparin or unfractionated heparin.
  • If a recurrent venous thromboembolism is diagnosed, the study medication should be stopped and the necessary clinical treatment initiated. After definitive confirmation of the diagnosis, unblinding of treatment group allocation should be performed, since a recurrent venous thromboembolism under therapeutic anticoagulation may require a different treatment approach (e.g. with low molecular weight heparin) compared to a thromboembolism recurrence under placebo.
  • If severe bleeding occurs, the trial medication should be stopped and the necessary treatment initiated. If an emergency reversal of the anticoagulant effect is necessary, unblinding should be considered.
  • If a pregnancy should occur, the study medication should be stopped and any further treatment initiated in accordance with the treating physician’s advice/prescription. Unblinding is necessary, since rivaroxaban is contraindicated during pregnancy.
  • To maintain blinding, we ask you to please refrain if possible from performing clotting tests or determining INR levels or anti-factor Xa activity.