Clinical trial NCT02479555: Lower-Limb Adventitial Infusion of DexaMethasone Via Bullfrog to Reduce Occurrence of Restenosis After Percutaneous Transluminal Angioplasty Revascularization
Official title: LIMBO-PTA: Lower-Limb Adventitial Infusion of DexaMethasone Via Bullfrog to Reduce Occurrence of Restenosis After Percutaneous Transluminal Angioplasty Revascularization
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Chronic Limb Ischemia
Lead sponsor: Mercator MedSystems, Inc.
Sponsor class: INDUSTRY
First posted: 2015-06-24
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Freedom from MALE
timeFrame: Up to 6 months following the procedure
measure: Freedom from CD-TLR
timeFrame: Up to 6 months following the procedure
measure: Composite clinical safety by freedom from adverse events including death, MALE, major unplanned amputation, or CD-TLR.
timeFrame: Up to 6 months following the procedure
measure: TVAL% change from post-procedure
timeFrame: 6 months following the procedure
Secondary outcomes:
measure: Composite clinical safety by freedom from adverse events including death, unplanned amputation, CD-TLR, SAE or MALE.
timeFrame: Up to 12 months following the procedure
measure: Event-free survival
timeFrame: 12 months following the procedure
measure: QVA change from post-procedure
timeFrame: 6 months following the procedure
measure: IVUS change from post-procedure
timeFrame: 6 months following the procedure
measure: Amputation-free survival
timeFrame: 30 days, 6 and 12 months post-procedure
measure: Major and minor amputations and amputation level
timeFrame: 30 days, 6 and 12 months post-procedure
measure: Change in foot wounds versus baseline
timeFrame: 30 days, 6 and 12 months post-procedure
measure: Resolved CLI death
timeFrame: 30 days, 6 and 12 months post-procedure
measure: CD-TLR
timeFrame: 30 days, 6 and 12 months post-procedure
measure: Primary sustained clinical improvement versus baseline
timeFrame: 30 days, 6 and 12 months post-procedure
measure: Secondary sustained clinical improvement versus baseline
timeFrame: 30 days, 6 and 12 months post-procedure
measure: SVS WIfI score versus baseline
timeFrame: 30 days, 6 and 12 months post-procedure
measure: EQ5D versus baseline
timeFrame: 30 days, 6 and 12 months post-procedure
measure: Walking capacity assessment versus baseline
timeFrame: 30 days, 6 and 12 months post-procedure
measure: SAE/MALE assessment
timeFrame: 30 days, 6 and 12 months post-procedure
measure: Inflammatory biomarker changes from baseline
timeFrame: 24 hours and 30 days
measure: Healthcare economic analysis
timeFrame: From baseline to 24 months
measure: Infusion technical success
timeFrame: Intra-procedural
measure: Revascularization success
timeFrame: Intra-procedural
Other outcomes:
Locations:
city: Bad Krozingen
country: Germany
facility: Universitäts-Herzzentrum Freiburg Bad Krozingen GmbH
city: Leipzig
country: Germany
facility: Universitätsklinikum Leipzig AöR
city: Sonneberg
country: Germany
facility: Medinos Kliniken des Landkreiss Sonneberg GmbH
Study officials:
affiliation: University Hospital of Leipzig
name: Dierk Scheinert, MD
role: PRINCIPAL_INVESTIGATOR
References: