Clinical trial NCT02179177: Apixaban in Patients With Sickle Cell Disease
Official title: Impact of Daily Prophylaxis Dose Anticoagulation With a Factor Xa Inhibitor (Apixaban) in Patients With Sickle Cell Disease
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Vaso-occlusive Crisis
Reduction in Hospitalizations
Sickle Cell Disease
Keywords: Vaso-occlusive crisis
Reduction in hospitalizations
Sickle Cell Disease
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: Bristol-Myers Squibb
First posted: 2014-07-01
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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

Primary outcomes:
measure: Change in Pain as Measured by Visual Analog Scale (VAS)
timeFrame: Month 1 to Month 8
Secondary outcomes:
measure: Change in Thrombin Generation Using D-dimer Measurement as a Surrogate
timeFrame: Enrollment to 2 months
measure: Daily Pain Scores While Hospitalized as Measured by VAS
timeFrame: up to 8 months
measure: Number of Hospitalizations During Treatment
timeFrame: up to 8 months
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
Study officials:
affiliation: Duke University
name: Nirmish Shah, MD
role: PRINCIPAL_INVESTIGATOR
References: