Lower-Limb Adventitial Infusion of DexaMethasone Via Bullfrog to Reduce Occurrence of Restenosis After Percutaneous Transluminal Angioplasty Revascularization

NCT ID: NCT02479555

Last Updated: 2020-02-20

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-01-31
• Study Completion Date: 2020-08-31

Brief Summary

This is a prospective, multi-center, randomized pilot study to document the effects of adventitial delivery of dexamethasone after balloon angioplasty of lesions below the knee in symptomatic patients with critical limb ischemia (CLI).

Detailed Description

This is a prospective, multi-center, randomized pilot study to document the effects of adventitial delivery of dexamethasone sodium phosphate injection (4 mg/mL) after balloon angioplasty of lesions below the knee in symptomatic patients with critical limb ischemia (CLI). Up to 120 patients (60 treatment and 60 control), including up to 20 Rutherford 6 patients (10 treatment and 10 control) at up to 30 sites in Europe and the United States. This study will assess the safety and effectiveness of Bullfrog Micro-Infusion Device adventitial deposition of dexamethasone in reducing inflammation and restenosis in patients with clinical evidence of chronic critical limb ischemia with an angiographically significant lesion in the infrapopliteal crural vessels.

Conditions

Chronic Limb Ischemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Treatment Group: Dexamethasone Delivery

Up to 60 angioplasty procedures at up to 30 sites in Europe and in the United States.

Patients will be randomized 1:1 to receive either the active treatment or control therapy.

Treatment Group: Standard endovascular revascularization therapy consisting of angioplasty followed by Dexamethasondihydrogenphosphat-dinatrium (Ph.Eur.) 4 mg/mL Injektionslösung and with or without stent placement. The drug is diluted to 3.2 mg/mL and administered to the adventitia per Bullfrog Instructions for Use in a dose of 0.8 mg dexamethasone (0.25 mL) per cm of desired vessel treatment length, up to 30 cm.

Group Type: ACTIVE_COMPARATOR

Dexamethasone sodium phosphate injection, USP, 4 mg/mL

Intervention Type: DRUG

Post-balloon angioplasty revascularization, the unblinded Pharmacist will prepare a sterile 20 mL syringe (Luer locking) with 16 mL of investigational drug or placebo per assignment. The unblinded Pharmacist provides syringe to investigator. Syringe shall only be labeled with the study number, patient number, randomization number and "Investigational Drug".

"Investigational Drug" will be administered via Bullfrog Micro-Infusion Device.

Control Group

Up to 60 angioplasty procedures at up to 30 sites in Europe and in the United States.

Patients will be randomized 1:1 to receive either the active treatment or control therapy. Control Group: Standard endovascular revascularization therapy consisting of angioplasty with or without stent placement. No specific distribution of gender regarding enrollment or randomization is intended. There will also be a separate randomization of patients with Rutherford 6 score to a maximum of 20 enrolled patients.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Dexamethasone sodium phosphate injection, USP, 4 mg/mL

Post-balloon angioplasty revascularization, the unblinded Pharmacist will prepare a sterile 20 mL syringe (Luer locking) with 16 mL of investigational drug or placebo per assignment. The unblinded Pharmacist provides syringe to investigator. Syringe shall only be labeled with the study number, patient number, randomization number and "Investigational Drug".

"Investigational Drug" will be administered via Bullfrog Micro-Infusion Device.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

Screening Criteria:

• Age ≥18 years
• Patient or patient's legal representative have been informed of the nature of the study, agrees to participate and has signed an IRB/EC approved consent form
• Female patients of childbearing potential have a negative pregnancy test ≤7 days before the procedure and are willing to use a reliable method of birth control for the duration of study participation
• Patient has documented chronic Critical Limb Ischemia (CLI) in the target limb from the popliteal artery to the ankle joint prior to the study procedure with Rutherford Category 4, 5 or 6
• Life expectancy >1 year in the Investigator's opinion

Angiographic Criteria:

• Successful revascularization of the TL with less than 30% residual stenosis, run-off down to the foot and direct in-line flow to any foot wound
• Reference vessel(s) diameter ≥2 mm
• Single or multiple atherosclerotic lesion ≥70% in at least one infrapopliteal crural target vessel including the tibioperoneal trunk that totals up to 30 cm in length (with no greater than 5 cm length of contiguous intervening normal artery), with possible extension into the popliteal artery distal to the center of the knee joint space (the P3 segment)

Exclusion Criteria

Screening Criteria:

• Patient unwilling or unlikely to comply with visit schedule
• Planned major index limb amputation
• Active foot infection; however, osteomyelitis in the toes or mild cellulitis around the perimeter of gangrene or small ulcers are not exclusions, but osteomyelitis of the metatarsal or more proximal region would be exclusionary
• Inability to receive study medications
• Estimated glomerular filtration rate (eGFR) less than 30 mL/min, except for patients with end stage renal disease on chronic hemodialysis
• Stage 3 (per SVS WIfI classification) or worse heel ulcers or heel ulcers that are determined to be primarily neuropathic in nature

Angiographic/Procedural Criteria:

• Hemodynamically significant inflow lesion (≥50% DS) or occlusion in the ipsilateral iliac, SFA, or popliteal arteries in which there is a failure to successfully treat and obtain a <30% residual stenosis
• Index lesion length is >30 cm as measured from proximal normal vessel to distal normal vessel
• Total length of lesions treated during the case (including target lesion, inflow lesions, and other non-index lesions) >50 cm
• Lesions revascularized during the index case but untreated by Bullfrog
• Use of alternative therapy, e.g. atherectomy, laser, or radiation therapy, as part of the index lesion treatment, or use of any drug eluting stents (DES) or drug-eluting balloon/drug-coated balloons (DEB/DCB) for treatment of any infra-inguinal lesions during the study procedure or during the initial six-month follow up period
• Previously implanted stent in the TL(s)
• Aneurysm in the target vessel
• Acute thrombus in the target limb
• Failure to cross the TL with a guide wire; however, subintimal wire crossing is allowed
• Heavy eccentric or concentric calcification at index lesion, which in the judgment of the investigator would prevent penetration of the Micro-Infusion Device needle through the vessel wall

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Mercator MedSystems, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Dierk Scheinert, MD

Role: PRINCIPAL_INVESTIGATOR

University Hospital of Leipzig

Locations

Universitäts-Herzzentrum Freiburg Bad Krozingen GmbH

Bad Krozingen, , Germany

Site Status: RECRUITING

Universitätsklinikum Leipzig AöR

Leipzig, , Germany

Site Status: RECRUITING

Medinos Kliniken des Landkreiss Sonneberg GmbH

Sonneberg, , Germany

Site Status: RECRUITING

Countries

Germany

Central Contacts

Kristen L. Poole, PhD

Role: CONTACT

kpoole@mercatormed.com

510-564-7761 ext. 818

Other Identifiers

CIP0169

Identifier Type: -

Identifier Source: org_study_id