The Effect of Rivaroxaban in Sickle Cell Disease

NCT02072668 | Completed Phase 2 Results DMC

• 2 other identifiers: 12-2607U01HL117659-01
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Sickle Cell Anemia; Sickle Cell-Beta0-Thalassemia

Keywords

sickle cell anemia; sickle cell disease; rivaroxaban; direct Xa inhibition; coagulation; anticoagulation

Outcome Measures

Primary Outcomes (2)

• Change From Baseline to 4 Weeks in Soluble Vascular Cell Adhesion Molecule-1 (VCAM-1)

  Assay performed for soluble VCAM-1 using a commercially available enzyme-linked immunosorbent assay (ELISA).

  Baseline, 4 weeks

• Change From Baseline to 4 Weeks in Interleukin-6 (IL-6)

  Assay performed for IL-6 using a commercially available enzyme-linked immunosorbent assay (ELISA).

  Baseline, 4 weeks

Secondary Outcomes (15)

• Change From Baseline to Week 4 in the Plasma Marker of Inflammation IL-2

  Baseline, 4 weeks

• Change From Baseline to Week 4 in the Plasma Marker of Inflammation IL-8

  Baseline, 4 weeks

• Change From Baseline to Week 4 in Plasma Marker of Inflammation hsCRP

  Baseline, 4 weeks

• Change From Baseline to Week 4 in Plasma Marker of Inflammation MPO

  Baseline, 4 weeks

• Change From Baseline to Week 4 in Plasma Marker of Inflammation TNF-a

  Baseline, 4 weeks

Study Arms (2)

Rivaroxaban for 4 wks, Placebo for 4 wks

OTHER

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.

Drug: rivaroxaban; Drug: placebo

Placebo for 4 wks, rivaroxaban for 4 wks

OTHER

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.

Drug: rivaroxaban; Drug: placebo

Interventions

rivaroxaban DRUG

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.

Also known as: Xarelto

Placebo for 4 wks, rivaroxaban for 4 wks; Rivaroxaban for 4 wks, Placebo for 4 wks

placebo DRUG

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.

Placebo for 4 wks, rivaroxaban for 4 wks; Rivaroxaban for 4 wks, Placebo for 4 wks

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

University of North Carolina - Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Related Publications (1)

• Ataga KI, Elsherif L, Wichlan D, Wogu AF, Matsui N, Pawlinski R, Cai J, Key NS. A pilot study of the effect of rivaroxaban in sickle cell anemia. Transfusion. 2021 Jun;61(6):1694-1698. doi: 10.1111/trf.16343. Epub 2021 Mar 4.

  PMID: 33660875 DERIVED

MeSH Terms

Conditions

Anemia, Sickle Cell; Thrombosis

Interventions

Rivaroxaban

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Thiophenes; Sulfur Compounds; Organic Chemicals; Morpholines; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Dr. Kenneth Ataga
• Organization: University of Tennessee Center for the Heath Sciences

kataga@uthsc.edu

901.448.3181

Study Officials

• Kenneth I Ataga, MBBS

  University of North Carolina, Chapel Hill

  PRINCIPAL INVESTIGATOR

• Nigel Key, MD

  University of North Carolina, Chapel Hill

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 24, 2014
• First Posted: February 26, 2014
• Study Start: February 1, 2014
• Primary Completion: October 4, 2018
• Study Completion: October 4, 2018
• Last Updated: April 13, 2020
• Results First Posted: April 13, 2020

Record last verified: 2020-03

Locations

US (1)