Perivascular Dexamethasone for Deep Vein Thrombosis

(DEXTERITY-AFP Trial)

Recruiting at 19 trial locations

Overseen By Kirk Seward, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Mercator MedSystems, Inc.

Must be taking: Anticoagulants, Antiplatelets

Disqualifiers: Pulmonary embolism, Severe renal impairment, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 1 day

80 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether delivering the anti-inflammatory drug dexamethasone around deep veins can prevent blood clots from reforming after a procedure to clear them. It targets individuals who have experienced symptoms of deep vein thrombosis (DVT) for 14 days or less before their procedure. Participants must be able to take medication orally and adhere to a specific medication routine. The trial compares the effects of drug delivery with a control group undergoing a similar procedure without the drug. The goal is to determine if this approach can improve symptoms and prevent further clots for up to two years. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant medical advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you will need to take certain medications like low molecular weight heparin and possibly an antiplatelet agent as part of the study.

What prior data suggests that this procedure is safe?

Research has shown that dexamethasone, the treatment under study, has been safely used in many patients. In a study with 70,000 high-risk patients, dexamethasone lowered the risk of blood clots, such as pulmonary embolism (a blockage in the lung) and deep vein thrombosis (a clot in a deep vein), in individuals with a history of clotting issues. Another study with 20 patients found very few problems over six months, and these patients experienced no major issues for at least a year.

Dexamethasone is already a well-known drug that reduces swelling and pain. Its safety in other conditions supports its use in clinical trials like this one. Although this study is still in the early stages, these findings suggest that dexamethasone is generally well-tolerated with minimal side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using perivascular dexamethasone for deep vein thrombosis (DVT) because it offers a unique approach compared to standard anticoagulant treatments like warfarin or heparin. Unlike these traditional options that primarily aim to prevent clot growth or formation, dexamethasone is a steroid that can reduce inflammation around the blood vessels. This anti-inflammatory effect may help to alleviate pain and swelling more effectively and could potentially enhance the healing process of the affected veins. The perivascular delivery method also means that the drug is applied directly where it’s needed, potentially increasing its effectiveness and minimizing systemic side effects.

What evidence suggests that this procedure is effective for preventing re-thrombosis after DVT recanalization?

Research has shown that using dexamethasone, a drug that reduces swelling, around the veins after a deep vein thrombosis (DVT) procedure may lower the risk of recurring blood clots. In this trial, participants in the treatment arm will receive dexamethasone, while those in the control arm will receive a sham comparator. One study found that only 5% of patients experienced post-thrombotic syndrome (long-term symptoms after a blood clot) after six months, with no moderate cases reported up to 12 months. This suggests that dexamethasone could help keep veins open and improve symptoms. The treatment aims to reduce swelling in the area, which may help prevent veins from closing again. ^{1 4 5 6 7}

Are You a Good Fit for This Trial?

Adults aged 18-89 with recent deep vein thrombosis (DVT) in the leg, who can take oral medication and agree to long-term anticoagulant therapy. They must not be enrolled in other drug/device trials, have a BMI over 45, severe health conditions that affect study participation or outcomes, known allergies to drugs used in the trial, or be pregnant/breastfeeding.

Inclusion Criteria

I can take pills and will follow the blood thinner plan.

For females of reproductive potential: use of highly effective contraception (abstinence is acceptable) for at least 1 month prior to study treatment (unless they had given birth within the 1 month prior to study treatment), and agreement to use such a method for at least 30 days after study treatment

I will be on a blood thinner for at least 13 months after my procedure.

Exclusion Criteria

You have had a stent placed in a vein on the same side of your body.

I have not had a bleeding stroke in the past year.

I have not had eye surgery or a bleeding eye condition in the last 3 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive local delivery of dexamethasone sodium phosphate injection around the deep veins after DVT recanalization using the Bullfrog® Micro-Infusion Device

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of PTS rate and primary patency

6 months

Multiple visits (in-person and virtual)

Long-term follow-up

Participants are monitored for long-term outcomes and symptom improvement

24 months

What Are the Treatments Tested in This Trial?

Interventions

• Dexamethasone

Trial Overview The trial is testing if injecting dexamethasone directly around veins after DVT removal reduces re-thrombosis and improves symptoms for up to two years. Participants will receive either this treatment or a sham procedure using the Bullfrog® Micro-Infusion Device.

How Is the Trial Designed?

Group I: Treatment Experimental Treatment 1 Intervention

Group II: Control Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

Mercator MedSystems, Inc.

Lead Sponsor

Trials

10

Recruited

1,100+

Sentara Norfolk General Hospital

Collaborator

Trials

12

Recruited

890+

Guy's and St Thomas' NHS Foundation Trust

Collaborator

Trials

399

Recruited

1,004,000+

Memorial Hermann Hospital

Collaborator

Trials

17

Recruited

56,300+

St. John Health System, Oklahoma

Collaborator

Trials

3

Recruited

240+

Stony Brook University

Collaborator

Trials

225

Recruited

41,700+

Charlotte-Mecklenburg Hospital

Collaborator

Trials

2

Recruited

140+

Northwestern University

Collaborator

Trials

1,674

Recruited

989,000+

Medstar Health Research Institute

Collaborator

Trials

202

Recruited

187,000+

Vascular Care Connecticut

Collaborator

Trials

2

Recruited

140+

Published Research Related to This Trial

In a study involving 73 patients undergoing percutaneous epidural adhesiolysis, dexamethasone sodium phosphate (DSP) demonstrated non-inferiority to triamcinolone acetate (TA) in reducing pain and improving function at the 6-month follow-up, with success rates of 62.5% for DSP compared to 45.2% for TA.

At 3 months, while DSP showed a higher mean percent decrease in pain scores (46.1%) compared to TA (42.4%), non-inferiority was not established until the 6-month mark, indicating that DSP may provide longer-lasting benefits in pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Percutaneous Epidural Adhesiolysis with Epidural Steroid Injection: A Non-inferiority Test of Non-particulate Steroids Versus Particulate Steroids. Cho, S., Park, HS.[2018]

Both perineural and intravenous dexamethasone effectively prolong the duration of analgesia in supraclavicular blocks, with no significant difference in duration (817.2 min vs. 858.0 min).

Perineural dexamethasone leads to a faster onset of both sensory (10.20 min vs. 11.60 min) and motor block (13.92 min vs. 14.96 min) compared to intravenous dexamethasone, making it a potentially more effective option for quicker pain relief.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Perineural and Intravenous Dexamethasone on Duration of Analgesia in Supraclavicular Brachial Plexus Block with Bupivacaine: A Comparative Study. Mathew, R., Radha, KR., Hema, VR.[2022]

In a study of 108 patients undergoing total knee arthroplasty, administering two doses of low-dose dexamethasone significantly reduced inflammatory markers (CRP and IL-6) and provided better pain relief compared to a placebo, particularly at 24 hours post-surgery.

Dexamethasone also decreased the incidence of postoperative nausea and vomiting (PONV) and postoperative fatigue, while showing no increase in the risk of surgical complications, indicating it is both effective and safe for enhancing recovery after knee surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two doses of low-dose perioperative dexamethasone improve the clinical outcome after total knee arthroplasty: a randomized controlled study. Xu, B., Ma, J., Huang, Q., et al.[2018]

In a study involving four patients with high intraocular pressure (IOP) responses to dexamethasone implants, the use of a XEN gel stent effectively normalized IOP, allowing continued treatment with dexamethasone, which was crucial for these patients.

After the XEN surgery, no further increases in IOP were observed following subsequent dexamethasone injections, suggesting that the XEN gel stent is a safe and effective option for managing steroid-induced ocular hypertension.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

XEN Gel Stent to Treat Intraocular Hypertension After Dexamethasone-Implant Intravitreal Injections: 5 Cases. Rezkallah, A., Mathis, T., Denis, P., et al.[2020]

In a study of 68 patients undergoing infraclavicular brachial plexus block, perineural dexamethasone significantly prolonged the duration of both motor block and analgesia compared to intravenous dexamethasone, with durations of 1768.13 minutes and 1743.59 minutes respectively versus 1245.94 minutes and 1310.16 minutes for the IV group (P < 0.001).

Patients receiving perineural dexamethasone experienced lower pain intensity and reduced need for rescue analgesia postoperatively, with only 9% reporting a Visual Analog Scale score of ≥3 compared to 37% in the intravenous group (P = 0.008).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of Perineural and Intravenous Dexamethasone as an Adjuvant to Levobupivacaine in Ultrasound-Guided Infraclavicular Brachial Plexus Block: A prospective Randomized Trial. Veena, G., Pangotra, A., Kumar, S., et al.[2022]

In a study of 35 eyes with retinal vein occlusion treated with an intravitreal dexamethasone implant, the ischaemic index remained stable over 6 months, indicating that dexamethasone treatment did not significantly change peripheral nonperfusion status.

Despite the stable ischaemic index, patients experienced improvements in best-corrected visual acuity and reductions in central retinal thickness, suggesting that dexamethasone is effective in improving visual outcomes even when peripheral perfusion status does not change.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extension of peripheral nonperfusion in eyes with retinal vein occlusion during intravitreal dexamethasone treatment. Rezar-Dreindl, S., Eibenberger, K., Buehl, W., et al.[2018]

A study involving 10,482 patients (137 receiving intravitreal dexamethasone and 10,345 receiving anti-VEGF) found that both treatments had similar risks for major systemic adverse events, indicating comparable safety profiles.

Both intravitreal dexamethasone and anti-VEGF medications were effective for treating ocular diseases, with no significant differences in systemic health markers or the need for glaucoma surgery between the two groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systemic Outcomes of Intravitreal Injections of Dexamethasone and Anti-Vascular Endothelial Growth Factor. Lin, TY., Hsieh, YT., Garg, SJ., et al.[2023]

In a study of 102 patients undergoing total knee arthroplasty, triamcinolone acetonide provided significantly better pain relief compared to dexamethasone, with lower pain scores at rest and during walking postoperatively.

Triamcinolone also resulted in lower C-reactive protein levels, indicating reduced inflammation, while both corticosteroids similarly increased fasting blood glucose levels without significant differences in postoperative nausea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The comparison of dexamethasone and triamcinolone periarticular administration in total knee arthroplasty: retrospective cohort study. Oshima, A., Hatayama, K., Terauchi, M., et al.[2022]

In a study of 18,872 hip and knee arthroplasties, a single low dose of dexamethasone (5-10 mg) did not increase the risk of post-operative prosthetic joint infections (PJIs), indicating its safety for use in these surgeries.

Dexamethasone effectively prevents post-operative nausea and vomiting (PONV) and may help reduce post-operative pain without raising infection rates, making it a beneficial option in multimodal pain management for arthroplasty patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Infection safety of dexamethasone in total hip and total knee arthroplasty: a study of eighteen thousand, eight hundred and seventy two operations. Vuorinen, MA., Palanne, RA., Mäkinen, TJ., et al.[2020]

In a study of 61 eyes treated with intravitreal dexamethasone implants for macular edema, 12% experienced elevated intraocular pressure (IOP) above 25 mmHg, particularly in patients with central retinal vein occlusion and glaucoma, indicating a need for careful monitoring in these subgroups.

The incidence of cataract surgery was notably high at 24% among treated phakic eyes, with the likelihood increasing with the number of implants, suggesting that repeated treatments may lead to a higher risk of cataract formation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

OBSERVED COMPLICATIONS FROM DEXAMETHASONE INTRAVITREAL IMPLANT FOR THE TREATMENT OF MACULAR EDEMA IN RETINAL VEIN OCCLUSION OVER 3 TREATMENT ROUNDS. Reid, GA., Sahota, DS., Sarhan, M.[2015]

Citations

1. clinicaltrial.be clinicaltrial.be/en/details/44624?per_page=100&recruiting=1&enrolling_by_invitation=1&active_not_recruiting=1&not_yet_recruiting=0&completed=0&only_recruiting=0&only_eligible=0

Perivenous Dexamethasone Therapy The goal of the study is to see if local anti-inflammation helps prevent re-thrombosis of the blood vessel and improvement in symptoms for up to ...

2. mercatormed.com mercatormed.com/six-month-outcomes-from-phase-one-trial-of-anti-inflammatory-drug-to-assess-benefit-in-acute-dvt-patients-demonstrate-promise/

Six-month outcomes from phase-one trial of anti- ... The 20-patient cohort, fully enrolled with six months of follow-up, showed a 5% rate of any PTS and currently no patients through 12 months with moderate-to- ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04858776

NCT04858776 | Perivenous Dexamethasone Therapy ... The goal of the study is to see if local anti-inflammation helps prevent re-thrombosis of the blood vessel and improvement in symptoms for up to 24 months after ...

4. sbir.gov sbir.gov/awards/213248

Award | SBIR Within 2 years of deep vein thrombosis (DVT) treatment, 50-60% of patients with iliofemoral thrombosis and 30-50% of all DVT patients regardless of thrombosis ...

5. withpower.com withpower.com/trial/phase-3-inflammation-5-2021-fec22

Perivascular Dexamethasone for Iliofemoral Thrombosis Trial Overview The trial tests whether injecting dexamethasone around deep veins after DVT recanalization reduces re-thrombosis risk and improves symptoms ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04862468

NCT04862468 | Perivenous Dexamethasone Therapy ... The goal of the study is to see if local anti-inflammation helps prevent re-thrombosis of the blood vessel and improvement in symptoms for up to 24 months after ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38735549/

An Analysis of 70000 High-Risk Patients The administration of DEX was associated with a decreased risk of PE and DVT in patients who have a history of VTE who underwent TJA.