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

NCT02479555 | Unknown Phase 2

• 1 other identifier: CIP0169
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 3

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).

Conditions

Chronic Limb Ischemia

Outcome Measures

Primary Outcomes (4)

• Freedom from MALE

  Freedom from major adverse limb event (MALE) within 6 months.

  Up to 6 months following the procedure

• Freedom from CD-TLR

  Freedom from clinically driven target lesion revascularization (CD-TLR) within 6 months.

  Up to 6 months following the procedure

• Composite clinical safety by freedom from adverse events including death, MALE, major unplanned amputation, or CD-TLR.

  Freedom from composite of death within 30 days from the index procedure, MALE, major unplanned amputation or CD-TLR within 6 months.

  Up to 6 months following the procedure

• TVAL% change from post-procedure

  Transverse-view vessel area loss percentage (TVAL%) of the target lesion at 6 months by quantitative vascular angiography (QVA) or prior to any CD-TLR of the target lesion before 6 months.

  6 months following the procedure

Secondary Outcomes (19)

• Composite clinical safety by freedom from adverse events including death, unplanned amputation, CD-TLR, SAE or MALE.

  Up to 12 months following the procedure

• Event-free survival

  12 months following the procedure

• QVA change from post-procedure

  6 months following the procedure

• IVUS change from post-procedure

  6 months following the procedure

• Amputation-free survival

  30 days, 6 and 12 months post-procedure

Study Arms (2)

Treatment Group: Dexamethasone Delivery

ACTIVE COMPARATOR

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.

Drug: Dexamethasone sodium phosphate injection, USP, 4 mg/mL

Control Group

NO INTERVENTION

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.

Interventions

Dexamethasone sodium phosphate injection, USP, 4 mg/mL 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.

Treatment Group: Dexamethasone Delivery

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• Screening Criteria:
• Patient unwilling or unlikely to comply with visit schedule
• Planned major index limb amputation
• 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

Sponsors & Collaborators

• Mercator MedSystems, Inc.: lead

Study Sites (3)

Universitäts-Herzzentrum Freiburg Bad Krozingen GmbH

Bad Krozingen, 79189, Germany

RECRUITING

Universitätsklinikum Leipzig AöR

Leipzig, 04103, Germany

RECRUITING

Medinos Kliniken des Landkreiss Sonneberg GmbH

Sonneberg, 96515, Germany

RECRUITING

MeSH Terms

Interventions

dexamethasone 21-phosphate

Study Officials

• Dierk Scheinert, MD

  University Hospital of Leipzig

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kristen L. Poole, PhD

CONTACT

510-564-7761; kpoole@mercatormed.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 15, 2015
• First Posted: June 24, 2015
• Study Start: January 1, 2016
• Primary Completion: August 1, 2020
• Study Completion: August 1, 2020
• Last Updated: February 20, 2020

Record last verified: 2020-02

Data Sharing

• IPD Sharing: Will not share

Locations

DE (3)