The Effect of Rivaroxaban in Sickle Cell Disease
Condition: Sickle Cell Anemia; Sickle Cell-Beta0-Thalassemia
MeSH terms: Anemia, Sickle Cell; Thalassemia
Study type: Interventional
Phase: Phase 2

Summary: 
      The primary study hypothesis is that inhibition of factor Xa with rivaroxaban will reduce
      inflammation, coagulation and endothelial cell activation, and improve microvascular blood
      flow in patients with sickle cell disease (SCD) during the non-crisis, steady state. To test
      this hypothesis, this study will evaluate the effects of rivaroxaban on:

        -  plasma markers of inflammation;

        -  plasma markers of endothelial activation;

        -  plasma markers of thrombin generation; and

        -  microvascular blood flow assessed using laser Doppler velocimetry (LDV) of
           post-occlusive reactive hyperemia (PORH).

      In a cross-over design, subjects will receive rivaroxaban 20 mg/day and placebo for 4 weeks
      each, separated by a 2-week washout phase.
    

Detailed description: 
      The study will consist of a Screening Phase, two Treatment Phases, a Wash-Out Phase, and a
      Follow-up Phase. The Screening Phase will occur within 28 days of randomization and will
      include informed consent, a physical examination, and complete medical history to include
      determination of sickle cell genotype and current medications. Clinical laboratory tests to
      be performed include: a Complete Blood Count (CBC) with differential and reticulocyte count;
      Prothrombin time(PT) / activated partial thromboplastin time (aPTT); and serum chemistries
      (BUN, creatinine, total and direct bilirubin, alanine aminotransferase (ALT), aspartate
      aminotransferase (AST), alkaline phosphatase, and LDH). A chest x-ray and MRI/MRA of the
      brain will also be done at Screening to rule out underlying disease.

      If the patient is found through the screening process to be eligible, the 1st Treatment Phase
      begins. Baseline safety assessments and measurement of biomarkers are completed, then the
      subject is randomized to receive rivaroxaban or placebo. After 4 weeks of treatment, there is
      a 2-Week Wash-Out Phase. After the Wash-Out Phase, another set of baseline studies are
      performed and the 2nd Treatment Phase begins. For this Phase of the study, the subject
      "crosses over" to receive whatever treatment - rivaroxaban or placebo - that they did not
      receive in the 1st Treatment Phase. After taking the assigned study drug for 4 weeks, the 2nd
      Treatment Phase ends. The subject returns 2 weeks after the last dose of study treatment for
      the Follow-Up Phase, consisting of a single end-of-study visit during which safety
      assessments are repeated.
    

Intervention name(s): rivaroxaban; placebo
Intervention type(s): Drug; Drug
Intervention description(s): Subject will receive rivaroxaban 20mg PO daily for 4 weeks and then matching placebo 1 PO daily for 4 weeks, with a 2-week wash out period in between the two treatment phases. Both of the two treatments will be in capsule form OR Subject will receive placebo 1 PO daily for 4 weeks, then rivaroxaban 20mg PO daily for 4 weeks, with a 2-week wash out period in between the two treatment phases. Both of the two treatments will be in capsule form.; Subject will receive rivaroxaban 20mg PO daily for 4 weeks and then matching placebo 1 PO daily for 4 weeks, with a 2-week wash out period in between the two treatment phases. Both of the two treatments will be in capsule form OR Subject will receive placebo 1 PO daily for 4 weeks, then rivaroxaban 20mg PO daily for 4 weeks, with a 2-week wash out period in between the two treatment phases. Both of the two treatments will be in capsule form.
Other intervention name(s): Xarelto
Intervention MeSH terms: Rivaroxaban
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: sickle cell anemia; sickle cell disease; rivaroxaban; direct Xa inhibition; coagulation; anticoagulation