Targeted Anticoagulation Therapy to Reduce Inflammation and Cellular Activation in Long-term HIV Disease
Condition: Inflammation; Coagulation; HIV Infection
MeSH terms: Inflammation
Intervention: Edoxaban 30mg daily; Matching placebo
Intervention MeSH terms: Edoxaban
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 44.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to evaluate the effects of pharmacologic FXa inhibition (via
      edoxaban 30 mg daily) on inflammation, as reflected in plasma Interleukin-6 levels.
    

Eligibility criteria:

        Inclusion Criteria

          -  HIV infection (verified by previous positive antibody or detectable HIV RNA level)

          -  Age ≥18 years

          -  Receiving continuous ART for ≥2 years (regimen changes >3 months prior to enrollment
             are acceptable)

          -  HIV RNA level ≤200 copies/mL for ≥1 year (1 measure ≥200 allowed if also <500 and
             preceded and followed by one or more values ≤200 copies/mL)

          -  D-dimer level ≥100 mg/L (or ng/mL) at screening (or within the prior month)

          -  Estimated creatinine clearance ≥50 mL/min

          -  Body weight ≥60kg

          -  Do not anticipate starting (or stopping) statin or aspirin therapy during the study

          -  For women of child bearing potential, agrees to use a reliable form of birth control

        Exclusion Criteria

          -  Pregnancy or breast feeding

          -  A contra-indication to taking edoxaban

          -  A clinical indication for anticoagulation therapy (e.g., atrial fibrillation or Deep
             Vein Thrombosis/PE)

          -  Treatment with anti-platelet, anti-coagulation, or immune-modulatory drugs currently
             or within the past 6 months; prior self-limited treatment with aspirin (i.e., not
             daily use) is not itself an exclusion.

          -  Grade ≥1 hematology lab abnormality for INR (>1.1 x ULN), hemoglobin (<10.0 g/L),
             platelets (<100,000 cells/μL), and WBC (2,500 cells/mm3)

          -  Grade ≥2 lab abnormality for chemistries (BMP) or liver panel

          -  Alcohol or illicit drug abuse/dependency within the prior year

          -  History of prior myocardial infarction or unstable atherosclerotic disease

          -  History of prior stroke or transient ischemic attack (TIA)

          -  History of active gastrointestinal ulcer or bleeding disorder within the prior year

          -  Intent to have surgery during the study period (12 months)

          -  Hepatitis C treatments (e.g., interferon, ribavirin, protease inhibitors) within the
             past 6 months

          -  Cirrhosis or hepatic impairment (e.g., Child-Pugh class B or C).

          -  Seizure disorder

          -  Previous/current CNS space occupying lesion (e.g., Toxoplasmosis, mTB) with persistent
             abnormalities on CNS imaging after completion of treatment.

          -  Surgical or invasive procedure anticipated during study period.

          -  Invasive cancer in the prior year or receiving cancer treatment (not including
             carcinoma-in-situ or basal cell cancer of the skin)

          -  Rheumatologic or inflammatory disease, systemic in nature (e.g., systemic lupus
             erythematosus, rheumatoid arthritis, vasculitis, sarcoidosis, Crohn's disease)

          -  Assessment by the clinical investigator that enrollment into the study could entail
             excess risk to the participant, beyond what is intended or expected.