Perivenous Dexamethasone to Reduce Venous Inflammation in Lower Extremity DVT: A Promising Approach in the Fight Against Post-Thrombotic Syndrome

Objective: The open-vein hypothesis, positing that thorough restoration of blood flow in lower-
extremity deep vein thrombosis (DVT) will stave off negative long-term post thrombotic syndrome (PTS),
has not proven sufficient. Residual inflammation of the vein wall even after thrombus is removed leads
to scar-like tissue, thickening and stiffening the vein wall and local valvular structures, and reducing the
vein’s capacitance. The DEXTERITY-AFP study aims to improve the outcomes of acute lower-extremity
deep vein thrombosis (DVT) treatment by investigating the effects of localized dexamethasone injection
alongside successful thrombus removal, addressing the persistent challenges of PTS and venous
inflammation-related complications.

Methods: Participants with acute iliofemoral or femoropopliteal DVT up to 50 cm in length including at
least the common femoral, femoral, and/or popliteal vein were screened for additional eligibility
criteria. Thrombus removal, including thrombolysis and/or thrombectomy, with possible venoplasty
and/or stenting, was performed at the discretion of the investigator. In the initial open-label phase
involving 20 patients, perivenous injections of dexamethasone sodium phosphate (4 mg/mL), diluted
20% with contrast medium, were then administered using the Bullfrog Micro-Infusion Device. Evaluation
endpoints encompassed major adverse events and ultrasound compressibility at 30 days, circulating
biomarker levels through 3 months, clinically relevant loss of primary patency at 6 months, and post-
thrombotic syndrome scores at 6-month intervals over 2 years. The trial has subsequently transitioned
to a dual-blinded, randomized, controlled phase with 60 participants to be enrolled.

Results: Preliminary data from 15 participants in the open-label cohort has demonstrated promising
results at 6-months, with 6.7% incidence of PTS and no occurrences of moderate-severe PTS. Average
Villalta score at 6 months was 1.73±0.53. In contrast, the ATTRACT trial reported 6-month Villalta scores
of 4.33±0.24 with anticoagulant therapy alone (n=285) and 3.11±0.24 for patients undergoing catheter-
directed thrombus removal (n=291). Average interleukin-6 level, a prominent marker expressed in the
inflammatory cascade, was found to drop 59% from baseline to one month after perivenous
dexamethasone administration (n=12). This is distinct from published results of the SOX study, in which
average IL-6 dropped from baseline to one-month follow-up by 48% in participants who did not go on to
develop PTS (n=347), and 43% in participants who developed PTS (n=327).

Conclusions: Addressing the challenge of venous inflammation in acute DVT, the open-label cohort of the
DEXTERITY-AFP trial showcases the potential of localized dexamethasone injection alongside thrombus
removal. Future endeavors include the dual-blinded randomized controlled arm of this study and the
DEXTERITY-SCI trial, targeting subacute and chronic DVT phases. This approach offers a promising
avenue to reduce symptoms and mitigate the burden of post-thrombotic complications.