The Effect of Rivaroxaban in Sickle Cell Disease

• Status: Completed
• Trial end date: 2018-10-04
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of North Carolina, Chapel Hill
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI)
• Treatments: Rivaroxaban

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
• 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.