Targeted Anticoagulation Therapy to Reduce Inflammation and Cellular Activation in Long-term HIV Disease

NCT ID: NCT02339415

Last Updated: 2019-09-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 44 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-07-31
• Study Completion Date: 2018-09-30

Brief 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.

Detailed Description

We hypothesize that increased generation of activated factor X (FXa) contributes to a systemic elevation in pro-inflammatory cytokine levels (e.g. IL-6) among HIV positive patients. This occurs, in part, via FXa activation of protease activated receptor 2 (PAR-2) on monocytes and tissue macrophages, which perpetuates innate inflammation. We will test our hypothesis with an oral antagonist to FXa (edoxaban), and quantify the immunologic effects of PAR-2 inhibition on systemic inflammation and monocyte activation.

The potential benefits of pharmacologic inhibition of FXa will be studied among HIV positive participants receiving ART with suppressed HIV viral load and a D-dimer >100 ng/mL. The study design is a cross-over placebo controlled randomized trial of edoxaban 30mg daily versus matched placebo (n=40 total participants). After screening and baseline visits, participants will be randomized to the sequence of drug administration (i.e., edoxaban vs. placebo). After randomization, participants will start study medication #1 and follow-up for visits at months 1, 2, 3 and 4. They will then stop study medication for 3 months, return for visits at months 7 and 8 (analogous to screening and baseline, respectively), then start study medication #2 and follow-up for visits at months 9, 10, 11, and 12.

The treatment effect (i.e., changes from pre-treatment levels) over 4 months will be assessed in measures of inflammation, immune activation, and coagulation. For comparisons with placebo, each participant will then serve as his or her own control in this cross-over design.

Conditions

Inflammation; Coagulation; HIV Infection

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Treatment

Edoxaban 30mg daily

Group Type: ACTIVE_COMPARATOR

Edoxaban 30mg daily

Intervention Type: DRUG

Placebo

Matching Placebo

Group Type: PLACEBO_COMPARATOR

Matching placebo

Intervention Type: DRUG

Interventions

Edoxaban 30mg daily

Intervention Type: DRUG

Matching placebo

Intervention Type: DRUG

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.

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

Sponsors

Hennepin Healthcare Research Institute

OTHER

Sponsor Role: lead

Responsible Party

Jason Baker

Protocol Chair

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jason Baker, M.D.

Role: PRINCIPAL_INVESTIGATOR

Hennepin Healthcare Research Institute

Locations

Hennepin County Medical Center

Minneapolis, Minnesota, United States

Hennepin County Medical Center

Minneapolis, Minnesota, United States

Countries

United States

Provided Documents

Document Type: Study Protocol, Statistical Analysis Plan, and Informed Consent Form

View Document

Other Identifiers

PCC-008

Identifier Type: -

Identifier Source: org_study_id