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

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ClinicalTrials.gov Identifier: NCT02339415
Recruitment Status : Active, not recruiting
First Posted : January 15, 2015
Last Update Posted : March 26, 2018
Sponsor:
Information provided by (Responsible Party):
Jason Baker, Hennepin Healthcare Research Institute.

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.

Condition or disease Intervention/treatment Phase
Inflammation Coagulation HIV Infection Drug: Edoxaban 30mg daily Drug: Matching placebo Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 44 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Targeted Anticoagulation Therapy to Reduce Inflammation and Cellular Activation in Long-term HIV Disease
Actual Study Start Date : July 2015
Estimated Primary Completion Date : December 2018
Estimated Study Completion Date : January 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Edoxaban

Arm Intervention/treatment
Active Comparator: Treatment
Edoxaban 30mg daily
Drug: Edoxaban 30mg daily
Placebo Comparator: Placebo
Matching Placebo
Drug: Matching placebo



Primary Outcome Measures :
  1. Interleukin 6 (IL-6) plasma levels [ Time Frame: 4 months ]
    Difference between treatment and control IL-6 plasma levels in change from pre-treatment to on-treatment values


Secondary Outcome Measures :
  1. Coagulation activity [ Time Frame: 4 months ]
    Difference between treatment and control D-Dimer levels in change from pre-treatment to on-treatment values



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02339415


Locations
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United States, Minnesota
Hennepin County Medical Center
Minneapolis, Minnesota, United States, 55415
Hennepin County Medical Center
Minneapolis, Minnesota, United States, 55417
Sponsors and Collaborators
Hennepin Healthcare Research Institute.
Investigators
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Principal Investigator: Jason Baker, M.D. Hennepin Healthcare Research Institute.

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Responsible Party: Jason Baker, Protocol Chair, Hennepin Healthcare Research Institute.
ClinicalTrials.gov Identifier: NCT02339415     History of Changes
Other Study ID Numbers: PCC-008
First Posted: January 15, 2015    Key Record Dates
Last Update Posted: March 26, 2018
Last Verified: March 2018

Additional relevant MeSH terms:
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Inflammation
HIV Infections
Acquired Immunodeficiency Syndrome
Pathologic Processes
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Edoxaban
Anticoagulants
Factor Xa Inhibitors
Antithrombins
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action