Apixaban in Patients With Sickle Cell Disease

NCT ID: NCT02179177

Last Updated: 2020-03-11

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-01-31
• Study Completion Date: 2017-09-03

Brief 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.

Detailed 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.

Conditions

Vaso-occlusive Crisis; Reduction in Hospitalizations; Sickle Cell Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Study Groups

Apixaban

Active drug Apixaban 2.5mg taken by mouth twice a day

Group Type: ACTIVE_COMPARATOR

Apixaban

Intervention Type: DRUG

Drug is taken by mouth twice a day for 6 months

Placebo

Sugar pills that look like Apixaban that will be taken by mouth twice a day

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Interventions

Apixaban

Drug is taken by mouth twice a day for 6 months

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: collaborator

Nirmish Shah

OTHER

Sponsor Role: lead

Responsible Party

Nirmish Shah

Assistant Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Nirmish Shah, MD

Role: PRINCIPAL_INVESTIGATOR

Duke University

Locations

Duke University Medical Center

Durham, North Carolina, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

Pro00048953

Identifier Type: -

Identifier Source: org_study_id