Apixaban in Patients With Sickle Cell Disease

Sickle Cell Disease Clinical Trial

Official title:

Impact of Daily Prophylaxis Dose Anticoagulation With a Factor Xa Inhibitor (Apixaban) in Patients With Sickle Cell Disease

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02179177
• Other study ID #: Pro00048953
• Status: Terminated
• Phase: Phase 3
• Start date: January 2015
• Est. completion date: September 3, 2017

Study information

• Verified date: February 2020
• Source: Duke University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

In patients with SCD, the use of low dose anticoagulation as an outpatient may lead to a significant decrease in morbidity and as a result, decrease healthcare utilization and costs. This study attempts to critically avoid admissions by reducing daily pain scores and pain crisis as an outpatient by use of a novel oral anticoagulant.

Description:

There is not only significant morbidity associated with patients with SCD, but also costs associated with the numerous hospitalizations. Small studies have been unable to show clear benefit of the use of low dose anticoagulation in SCD due to limited sample size or the inclusion of very specific populations. However, studies have shown a decrease in the level of elevated prothrombotic markers with anticoagulation, and one study using full dose anticoagulation in patients with a generally milder form of SCD (with high protective hemoglobin) showed more rapid decrease in clinical pain with use of anticoagulation, suggesting a possible benefit of such therapy. Due to the paucity of data to support therapeutic dose LMWH in the more severe forms of SCD seen in the United States, we have chosen prophylactic dose anticoagulation. This study proposal attempts to critically avoid admissions by reducing daily pain scores and pain crisis as an outpatient by use of a novel oral anticoagulant.

The development of novel anticoagulants such as oral direct factor Xa (FXa) inhibitors allows the realistic use of daily prophylactic dosing as an outpatient. Past studies as detailed earlier have been limited by attempts to use subcutaneous injections or frequent, close monitoring for acenocoumarol treatment, both which are not ideal for chronic daily use. Furthermore, the use of global assays such calibrated automated thrombography (CAT) have shown further details about thrombin generation in a population which is hypercoagulable at baseline.

This is a double blind, parallel group, placebo controlled feasibility study with an enrollment target of 25 patients (12 per arm). All subjects that meet inclusion criteria as an outpatient, following a 1 month observation, will be randomized to receive an oral prophylactic dose factor Xa inhibitor (Apixaban 2.5mg po bid) or placebo for 6 months. Subjects will return for a 30 day (+/- 5 days) follow-up visit after the End of Treatment (EOT) visit. Initial randomization will occur by computerized randomization technique by the investigational drug services (IDS) at Duke University Medical Center.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 16
• Est. completion date: September 3, 2017
• Est. primary completion date: September 3, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• documented HgbSS, SC or HgbS-beta0 thalassemia,

• age =18 years old and =80,

• seen in outpatient clinic =2 times in past year

• seen for an acute care visit (hospitalization, emergency department, or day hospital visit) for pain >2 times in the past year.

Exclusion Criteria:

• Hospitalization or day hospital visit for pain crisis within the past 2 weeks

• Patients with =10 acute care visits within the past year will be excluded

• Creatinine >3.0 mg/dL

• creatinine =1.5 mg/dL AND weight =60 kg

• chronic use of antiplatelet or anticoagulation medication

• Patients with known vasculopathy or Moya-Moya

• platelet count <100 X 109/L

• AST or ALT >3 times normal

• chronic red blood cell transfusions (scheduled transfusions)

• packed red blood cell transfusion within the past 2 months

• Use of CYP3A4 and P-gp inhibitor medications

Related Conditions & MeSH terms

• Anemia, Sickle Cell
• Reduction in Hospitalizations
• Sickle Cell Disease
• Vaso-occlusive Crisis

Intervention

Drug:
• Apixaban
Drug is taken by mouth twice a day for 6 months
• Placebo

Locations

Country	Name	City	State
United States	Duke University Medical Center	Durham	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Nirmish Shah	Bristol-Myers Squibb

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Pain as Measured by Visual Analog Scale (VAS)	The primary pain assessment tool will be a 10-cm horizontal visual analog scale (VAS), with "0" corresponding to no pain at one end and "10" indicating the worst pain at the other.	Month 1 to Month 8
Secondary	Change in Thrombin Generation Using D-dimer Measurement as a Surrogate		Enrollment to 2 months
Secondary	Daily Pain Scores While Hospitalized as Measured by VAS	The primary pain assessment tool will be a 10-cm horizontal visual analog scale (VAS), with "0" corresponding to no pain at one end and "10" indicating the worst pain at the other. Secondary analysis will be performed to evaluate differences when patients are hospitalized and on study drug versus placebo.	up to 8 months
Secondary	Number of Hospitalizations During Treatment		up to 8 months