The Effect of Rivaroxaban in Sickle Cell Disease
Condition: Sickle Cell Anemia; Sickle Cell-Beta0-Thalassemia
MeSH terms: Anemia, Sickle Cell; Thalassemia
Intervention: rivaroxaban; placebo
Intervention description: 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.
Intervention MeSH terms: Rivaroxaban
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 14.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: sickle cell anemia; sickle cell disease; rivaroxaban; direct Xa inhibition; coagulation; anticoagulation

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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  18 to 65 years of age; sickle cell anemia (HbSS) or sickle-beta0 (HbSβ0) thalassemia;

          -  serum creatinine ≤ 1.0 mg/dL men) or 1.2 mg/dL (women);

          -  ALT </= 2 times upper limits of normal;

          -  platelet count ≥ 50,000 cu/mm;

          -  normal baseline PT/international normalized ratio (INR) and aPTT;

          -  be in the non-crisis, "steady state" with no severe pain episodes during the preceding
             4 weeks;

          -  ability to understand the requirements of the study and be willing to give informed
             consent;

          -  women of childbearing age must be practicing an adequate method of contraception;

          -  and if on hydroxyurea, be on a stable dose for at least 3 months prior to enrollment.

        Exclusion Criteria:

          -  hypersensitivity to any component of rivaroxaban;

          -  history of major GI bleeding or bleeding diathesis;

          -  baseline Hb < 5.5 gm/dL;

          -  history of clinically overt stroke;

          -  brain magnetic resonance imaging with angiography (MRI/MRA) scan with evidence of Moya
             Moya;

          -  pregnant or breastfeeding;

          -  active liver disease or ALT > 3 times upper limit of normal;

          -  on chronic anticoagulant, non-steroidal anti-inflammatory (NSAID) or statin therapy;

          -  history of metastatic cancer;

          -  current alcohol abuse;

          -  on a chronic transfusion program or any blood transfusion in the 3 months prior to
             enrollment;

          -  ingested any investigational drugs within the past 4 weeks;

          -  use of CYP3A4/P-glycoprotein inducers such as carbamazepine, phenytoin, rifampin, and
             St John's wort;

          -  use of CYP3A4/P- glycoprotein inhibitors such as ketoconazole, indinavir/ritonavir,
             itraconazole, lopinavir/ritonavir, ritonavir, and conivaptan.