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Apixaban in Patients With Sickle Cell Disease

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ClinicalTrials.gov Identifier: NCT02179177
Recruitment Status : Terminated (funding has been exhausted)
First Posted : July 1, 2014
Results First Posted : March 11, 2020
Last Update Posted : March 11, 2020
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
Nirmish Shah, Duke University

Tracking Information
First Submitted Date  ICMJE June 27, 2014
First Posted Date  ICMJE July 1, 2014
Results First Submitted Date  ICMJE February 24, 2020
Results First Posted Date  ICMJE March 11, 2020
Last Update Posted Date March 11, 2020
Study Start Date  ICMJE January 2015
Actual Primary Completion Date September 3, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 27, 2020)
Change in Pain as Measured by Visual Analog Scale (VAS) [ Time Frame: Month 1 to Month 8 ]
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.
Original Primary Outcome Measures  ICMJE
 (submitted: June 27, 2014)
Mean daily pain score in outpatients with SCD [ Time Frame: 6 months ]
After randomization and initial blood draw,patients will be given a daily pain log. Patients record daily pain scores and return in 1 month (+/- 5 days) at which time patients will be given a 1 month supply of study drug. Patients will return monthly (+/- 5 days) to return daily pain logs, verify compliance to medication, review completion of daily pain logs, and give additional study drug for the next month. Patients must adhere to daily administration of study drug and miss no more than 2 doses per week. Clinical pain scores will also be performed with each visit. 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. The daily pain log will include the VAS and if the patient classifies their pain as 'crisis' or not. Patients will be called monthly between in person visits to assess for AE/SAE and to reinforce the importance of medication compliance.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 27, 2020)
  • Change in Thrombin Generation Using D-dimer Measurement as a Surrogate [ Time Frame: Enrollment to 2 months ]
  • Daily Pain Scores While Hospitalized as Measured by VAS [ Time Frame: up to 8 months ]
    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.
  • Number of Hospitalizations During Treatment [ Time Frame: up to 8 months ]
Original Secondary Outcome Measures  ICMJE
 (submitted: June 27, 2014)
  • Change in thrombin generation from enrollment to 2 months following initiation of study drug. [ Time Frame: Enrollment to 2 months ]
    The investigator will analyze the change in thrombin generation from enrollment to 2 months following initiation of study drug. The investigator hypothesizes that the anticoagulation drug will cause a decrease in thrombin generation from baseline to two months. From the literature the standard deviation of the D-dimer measure per patient is 500. With a total of 60 patients randomized equally to each drug sequence, and conservatively assuming no correlation between D-dimer values from baseline to 2 months on the same patient, we achieve a power of 0.863 to detect a mean D-dimer difference in the change from baseline to 2 months between the placebo and the daily prophylactic anticoagulation dose groups of 250 mg/l {= [(1000-750) - (1000-1000)] mg/l} for a one-sided 0.05 test.
  • Comparison of daily pain scores while hospitalized between treatment arms [ Time Frame: 6 months ]
    Secondary analysis will be performed to evaluate differences when patients are hospitalized and on study drug versus placebo, as well as healthcare utilization for patients treated with Apixaban.
  • Number of hospitalizations during each treatment period. [ Time Frame: 6 months ]
    Secondary analysis will be performed to evaluate differences when patients are hospitalized and on study drug versus placebo, as well as healthcare utilization for patients treated with Apixaban.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Apixaban in Patients With Sickle Cell Disease
Official Title  ICMJE Impact of Daily Prophylaxis Dose Anticoagulation With a Factor Xa Inhibitor (Apixaban) in Patients With Sickle Cell Disease
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Prevention
Condition  ICMJE
  • Vaso-occlusive Crisis
  • Reduction in Hospitalizations
  • Sickle Cell Disease
Intervention  ICMJE
  • Drug: Apixaban
    Drug is taken by mouth twice a day for 6 months
  • Drug: Placebo
Study Arms  ICMJE
  • Active Comparator: Apixaban
    Active drug Apixaban 2.5mg taken by mouth twice a day
    Intervention: Drug: Apixaban
  • Placebo Comparator: Placebo
    Sugar pills that look like Apixaban that will be taken by mouth twice a day
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: April 15, 2019)
16
Original Estimated Enrollment  ICMJE
 (submitted: June 27, 2014)
60
Actual Study Completion Date  ICMJE September 3, 2017
Actual Primary Completion Date September 3, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02179177
Other Study ID Numbers  ICMJE Pro00048953
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Nirmish Shah, Duke University
Study Sponsor  ICMJE Nirmish Shah
Collaborators  ICMJE Bristol-Myers Squibb
Investigators  ICMJE
Principal Investigator: Nirmish Shah, MD Duke University
PRS Account Duke University
Verification Date February 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP