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

Phase 2

Completed

• Conditions: Inflammation; Coagulation; HIV Infection
• Interventions: Drug: Matching placebo; Drug: Edoxaban 30mg daily

• Registration Number: NCT02339415
• Lead Sponsor: 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.

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.

Study Timeline

• Study First Submitted: 2015-01-12
• Study First Submitted QC: 2015-01-14
• Study First Posted: 2015-01-15
• Study Start: 2015-07
• Primary Completion: 2018-09
• Study Completion: 2018-09
• Results First Submitted: 2019-02-17
• Status Verified: 2019-08
• Results First Submitted QC: 2019-08-15
• Last Update Submitted: 2019-08-15
• Results First Posted: 2019-09-06
• Last Update Posted: 2019-09-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 44

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Placebo	Matching placebo	Matching Placebo
Treatment	Edoxaban 30mg daily	Edoxaban 30mg daily

Primary Outcome Measures

Name	Time	Method
Change in Interleukin 6 (IL-6) Plasma Levels From Baseline to 4 Months.	Through study completion, an average of 4 months on each treatment.	Difference between treatment and control ln-transformed IL-6 plasma levels in change from pre-treatment to on-treatment values

Secondary Outcome Measures

Name	Time	Method
Change in D-Dimer Levels From Baseline to 4 Months	Through study completion, an average of 4 months on each treatment.	Difference between treatment and control ln-transformed D-Dimer levels in change from pre-treatment to on-treatment values

Trial Locations

Locations (1)

Hennepin County Medical Center; 🇺🇸 Minneapolis, Minnesota, United States