Perivascular Dexamethasone for Iliofemoral Thrombosis

(DEXTERITY-SCI Trial)

Recruiting at 14 trial locations

Overseen By Kirk Seward, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Mercator MedSystems, Inc.

Must be taking: Anticoagulants, Antiplatelets

Must not be taking: Heparin, rtPA, Dexamethasone

Disqualifiers: Obesity, Non-ambulatory, PE, 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 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 1 day

60 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a study of a medical procedure that utilizes a commercially available catheter (the Bullfrog® Micro-Infusion Device) to locally deliver a commercially available anti-inflammatory drug (dexamethasone sodium phosphate injection) around the deep veins after DVT recanalization, where DVT symptoms were present for at least 14 days and no more than 60 days prior to recanalization. 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 the initial DVT recanalization procedure.

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 must be able to take oral medication and follow a prescribed anticoagulant regimen, including low molecular weight heparin and an antiplatelet agent like aspirin.

What data supports the effectiveness of the drug Perivascular Dexamethasone for Iliofemoral Thrombosis?

The research shows that dexamethasone, particularly in the form of an intravitreal implant (Ozurdex), is effective in treating conditions like diabetic macular edema and retinal vein occlusion by reducing swelling and improving vision. This suggests that dexamethasone has anti-inflammatory properties that could potentially be beneficial in treating other conditions involving inflammation, such as iliofemoral thrombosis. ^{1 2 3 4 5}

Is dexamethasone generally safe for use in humans?

Dexamethasone, particularly in the form of an implant called Ozurdex, is considered relatively safe with few adverse events reported, although rare side effects can occur. ^{3 4 6 7 8}

What makes perivascular dexamethasone unique for treating iliofemoral thrombosis?

Perivascular dexamethasone is unique because it is delivered directly around blood vessels, allowing high local concentrations of the drug to reduce inflammation and prevent complications like restenosis (re-narrowing of blood vessels) after vascular injury, which is not typically achieved with standard systemic treatments. ^{5 9 10 11 12}

Eligibility Criteria

Adults aged 18-89 with recent (14-60 days) iliofemoral DVT needing stenting, able to take oral meds and adhere to anticoagulant regimen. Must not have active cancer, severe health issues, or be pregnant/breastfeeding. BMI must be under 40, and they should agree to contraception if applicable.

Inclusion Criteria

My targeted vein was successfully reopened and has at least one working inflow vein.

I have been on aspirin or a P2Y12 inhibitor for at least 30 days.

I have a significant blood clot in my leg that blocks more than half of the blood flow.

Exclusion Criteria

You have had a condition called heparin-induced thrombocytopenia in the past or are currently experiencing it.

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

I do not have active bleeding, recent severe GI issues, or serious liver problems.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo DVT recanalization and receive local delivery of dexamethasone using the Bullfrog® Micro-Infusion Device

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness, including primary patency and freedom from major adverse events

6 months

Multiple visits (in-person and virtual)

Long-term follow-up

Participants are monitored for improvement in symptoms and prevention of re-thrombosis

24 months

Treatment Details

Interventions

• Perivascular dexamethasone
• Perivascular sham

Trial Overview The trial tests whether injecting dexamethasone around deep veins after DVT recanalization reduces re-thrombosis risk and improves symptoms over two years compared to a sham procedure using the Bullfrog® Micro-Infusion Device.

Participant Groups

Group I: Treatment Experimental Treatment 1 Intervention

Group II: Control Placebo Group 1 Intervention

Perivascular dexamethasone is already approved in United States, European Union for the following indications:

Approved in United States as Dexamethasone for:

• Allergic reactions
• Arthritis
• Blood/hormone disorders
• Skin diseases
• Eye problems
• Breathing problems
• Bowel disorders
• Cancer
• Immune system disorders
• Adrenal insufficiency
• Cerebral edema
• Shock

Approved in European Union as Dexamethasone for:

• Acute adrenocortical insufficiency
• Relative adrenocortical insufficiency
• Cerebral oedema
• Eye disorders
• Neoplastic states
• Endocrine disorders
• Preoperative and postoperative support
• Shock

Who Is Running the Clinical Trial?

Mercator MedSystems, Inc.

Lead Sponsor

Trials

10

Recruited

1,100+

Vascular Care Connecticut

Collaborator

Trials

2

Recruited

140+

University of South Florida

Collaborator

Trials

433

Recruited

198,000+

OhioHealth Research Institute

Collaborator

Trials

3

Recruited

160+

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+

Sentara Norfolk General Hospital

Collaborator

Trials

12

Recruited

890+

Medstar Health Research Institute

Collaborator

Trials

202

Recruited

187,000+

Guy's and St Thomas' NHS Foundation Trust

Collaborator

Trials

399

Recruited

1,004,000+

Findings from Research

In a study of 31 patients receiving 1-3 dexamethasone (DEX) implants for retinal vein occlusion with macular edema, there was a moderate increase in intraocular pressure (IOP) observed, particularly at one month after injection.

Despite the increase in IOP, the DEX implants did not show significant negative effects on corneal endothelial health, as measured by endothelial cell density, cell size variation, and corneal thickness over a follow-up period of nearly 10 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of intravitreal injection of dexamethasone implant on corneal endothelium in macular edema due to retinal vein occlusion. Ilhan, N., Coskun, M., Ilhan, O., et al.[2015]

Dexamethasone, particularly in the form of the intravitreal implant (DEX implant), has been recognized as an effective treatment for diabetic macular oedema (DMO), which is a major cause of vision loss in working-age individuals.

The DEX implant has been approved by the FDA and EU for treating macular oedema related to retinal vein occlusion and non-infectious uveitis, highlighting its safety and efficacy in managing these eye conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of the Dexamethasone Intravitreal Implant for Treatment of Patients with Diabetic Macular Oedema. Dutra Medeiros, M., Alkabes, M., Nucci, P.[2020]

In a study of 9 patients with retinal vein occlusion and macular edema, treatment with a sustained-release dexamethasone implant led to a significant reduction in central retinal thickness and improved visual acuity, with 40% of patients gaining at least 10 letters in best-corrected visual acuity after 3 months.

The safety profile of the dexamethasone implant was favorable, showing no serious adverse events, and the treatment effectively resolved macular edema, although visual outcomes were better in patients with intact photoreceptor layers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SD-OCT pattern of retinal venous occlusion with cystoid macular edema treated with Ozurdex®. Coscas, G., Coscas, F., Zucchiatti, I., et al.[2022]

The 0.7 mg dexamethasone implant (Ozurdex) is primarily used to treat diabetic macular edema and retinal vein occlusion-related edema.

This case report highlights a previously unreported side effect of the dexamethasone implant, indicating the need for further investigation into its safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A New Side Effect of Intravitreal Dexamethasone Implant (Ozurdex®). Eris, E., Erdogan, G., Perente, I., et al.[2020]

The dexamethasone intravitreal implant (Ozurdex) effectively promotes the resolution of macular edema and improves visual acuity in patients with retinal vein occlusions.

The improvement in visual acuity may vary based on factors like the duration of the disease and the location of the occlusion, highlighting the importance of individualized treatment approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical efficacy of dexamethasone intravitreal implant (Ozurdex) in patients with retinal vein occlusions]. Kulagina, AV., Gusarevich, OG., Gusarevich, AA., et al.[2014]

Dexamethasone implant (Ozurdex™) is generally considered a safe treatment with minimal adverse events, highlighting its favorable safety profile.

The study presents a rare case of a fractured Ozurdex™ implant occurring immediately after injection, providing insights into potential complications and their outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fractured dexamethasone implant (OZURDEX®) following intravitreal injection. Aljohani, SM., Al-Shehri, AM., Al-Rubaie, KR.[2021]

In a study of 10 patients with persistent Macular Edema due to Retinal Vein Occlusion, 9 out of 10 experienced improvement in visual acuity and reduction in retinal thickness after receiving repeated Ozurdex implants, indicating its efficacy as a treatment option when previous anti-VEGF therapies failed.

While Ozurdex was generally safe, with no serious adverse events reported, the study noted a relatively high incidence of cataract progression (10%) and intraocular pressure elevation (20%), suggesting the need for careful monitoring and further research to assess long-term safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of dexamethasone intravitreal implant (Ozurdex) for the treatment of persistent macular edema secondary to retinal vein occlusion in eyes previously treated with anti-vascular endothelial growth factors. Tservakis, I., Koutsandrea, C., Papaconstantinou, D., et al.[2019]

The dexamethasone intravitreal implant (0.7 mg) significantly improved visual acuity and reduced central retinal thickness in patients with macular edema due to retinal vein occlusion, showing a faster response compared to the sham treatment over a six-month period.

While the most common side effect was increased intraocular pressure, it was manageable with topical medication, and mean pressure levels returned to normal by month 4, indicating a favorable safety profile for DEX in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of dexamethasone intravitreal implant for treatment of macular edema secondary to retinal vein occlusion in Chinese patients: randomized, sham-controlled, multicenter study. Li, X., Wang, N., Liang, X., et al.[2023]

In a study of 90 patients undergoing total knee arthroplasty, the combination of intravenous and topical dexamethasone significantly reduced postoperative pain and swelling compared to a control group receiving saline.

Patients receiving dexamethasone also experienced improved functional recovery, with greater range of motion and ambulation distance, as well as a lower incidence of postoperative nausea and vomiting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of combining intravenous and topical dexamethasone against postoperative pain and function recovery after total knee arthroplasty: A prospective, double-blind, randomized controlled trial. Wu, C., Luo, D., Zhu, Y., et al.[2023]

A 71-year-old man experienced worsening vitreomacular traction (VMT) after receiving the dexamethasone intravitreal implant (Ozurdex) for macular edema caused by central retinal vein occlusion (CRVO).

The case highlights that VMT can become more noticeable and may worsen after the resolution of macular edema following treatment with Ozurdex, indicating a potential complication of this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evolution of vitreomacular traction following the use of the dexamethasone intravitreal implant (Ozurdex) in the treatment of macular edema secondary to central retinal vein occlusion. Bakri, SJ., Omar, AF.[2013]

Local delivery of dexamethasone using a drug-eluting polymer cuff effectively inhibits neointima formation in a mouse model of restenosis without causing systemic side effects, unlike systemic dexamethasone treatment which resulted in weight loss.

However, the local delivery of dexamethasone is associated with dose-dependent adverse effects on vascular morphology, including medial atrophy and increased apoptosis, indicating potential risks to vascular integrity despite its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Histopathologic alterations following local delivery of dexamethasone to inhibit restenosis in murine arteries. Pires, NM., Schepers, A., van der Hoeven, BL., et al.[2013]

Local delivery of dexamethasone using periadventitial polymer systems significantly reduces neointimal proliferation after balloon vascular injury in a rat model, with a 76% reduction observed with 5% dexamethasone and 75% with 0.5% dexamethasone compared to placebo.

The study indicates that the silicone polymers did not cause neointimal proliferation without balloon injury, suggesting that the drug delivery system is effective and site-specific for preventing vascular complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Local delivery of dexamethasone for prevention of neointimal proliferation in a rat model of balloon angioplasty. Villa, AE., Guzman, LA., Chen, W., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Effect of intravitreal injection of dexamethasone implant on corneal endothelium in macular edema due to retinal vein occlusion. [2015]

2. England pubmed.ncbi.nlm.nih.gov

Effectiveness of the Dexamethasone Intravitreal Implant for Treatment of Patients with Diabetic Macular Oedema. [2020]

3. United States pubmed.ncbi.nlm.nih.gov

SD-OCT pattern of retinal venous occlusion with cystoid macular edema treated with Ozurdex®. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

A New Side Effect of Intravitreal Dexamethasone Implant (Ozurdex®). [2020]

5. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Clinical efficacy of dexamethasone intravitreal implant (Ozurdex) in patients with retinal vein occlusions]. [2014]

6. India pubmed.ncbi.nlm.nih.gov

Fractured dexamethasone implant (OZURDEX®) following intravitreal injection. [2021]

7. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Safety and efficacy of dexamethasone intravitreal implant (Ozurdex) for the treatment of persistent macular edema secondary to retinal vein occlusion in eyes previously treated with anti-vascular endothelial growth factors. [2019]

8. Germany pubmed.ncbi.nlm.nih.gov

Safety and efficacy of dexamethasone intravitreal implant for treatment of macular edema secondary to retinal vein occlusion in Chinese patients: randomized, sham-controlled, multicenter study. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Efficacy of combining intravenous and topical dexamethasone against postoperative pain and function recovery after total knee arthroplasty: A prospective, double-blind, randomized controlled trial. [2023]

10. United States pubmed.ncbi.nlm.nih.gov

Evolution of vitreomacular traction following the use of the dexamethasone intravitreal implant (Ozurdex) in the treatment of macular edema secondary to central retinal vein occlusion. [2013]

11. England pubmed.ncbi.nlm.nih.gov

Histopathologic alterations following local delivery of dexamethasone to inhibit restenosis in murine arteries. [2013]

12. United States pubmed.ncbi.nlm.nih.gov

Local delivery of dexamethasone for prevention of neointimal proliferation in a rat model of balloon angioplasty. [2022]