Lower-Limb Adventitial Infusion of DexaMethasone Via Bullfrog to Reduce Occurrence of Restenosis After Atherectomy (ATX)-Based Revascularization (LIMBO-ATX)
![]() |
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
ClinicalTrials.gov Identifier: NCT02479620 |
Recruitment Status : Unknown
Verified February 2020 by Mercator MedSystems, Inc..
Recruitment status was: Active, not recruiting
First Posted : June 24, 2015
Last Update Posted : February 19, 2020
|
- Study Details
- Tabular View
- No Results Posted
- Disclaimer
- How to Read a Study Record
Condition or disease | Intervention/treatment | Phase |
---|---|---|
Chronic Limb Ischemia | Drug: Dexamethasone Sodium Phosphate Injection, USP, 4 mg/mL | Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 120 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | Single (Participant) |
Primary Purpose: | Treatment |
Official Title: | LIMBO-ATX: Lower-Limb Adventitial Infusion of DexaMethasone Via Bullfrog to Reduce Occurrence of Restenosis After Atherectomy (ATX)-Based Revascularization |
Actual Study Start Date : | June 2016 |
Actual Primary Completion Date : | November 2019 |
Estimated Study Completion Date : | March 2020 |

Arm | Intervention/treatment |
---|---|
Active Comparator: Dexamethasone Delivery
Up to 60 atherectomy-based revascularization procedures at up to 30 sites in the United States and Europe. For Subjects randomized into the Dexamethasone Delivery arm, this protocol will utilize a 4 mg/mL preparation of Dexamethasone Sodium Phosphate Injection, USP. Each milliliter of the solution contains 4.37 mg of dexamethasone sodium phosphate equivalent to 4 mg of dexamethasone phosphate or 3.33 mg of dexamethasone. The total dose of Dexamethasone Sodium Phosphate Injection, USP will be diluted by 20% prior to infusion. This will result in a final concentration of 3.2 mg dexamethasone phosphate (3.5 mg dexamethasone sodium phosphate, or 2.67 mg dexamethasone) in each milliliter of solution. |
Drug: Dexamethasone Sodium Phosphate Injection, USP, 4 mg/mL
Following atherecomy-based revascularization, Investigators will be unblinded to assignment and will treat only patients assigned to the treatment arm with the Bullfrog delivery of dexamethasone. |
No Intervention: Control
Up to 60 atherectomy-based revascularization procedures at up to 30 sites in the United States and Europe. Standard endovascular revascularization therapy consisting of atherectomy with or without angioplasty and with or without stent placement. No additional drug will be given to Subjects randomized to Control. |
- Freedom from MALE [ Time Frame: Up to 6 Months following the procedure ]Freedom from major adverse limb event (MALE) within 6 months.
- Freedom from CD-TLR [ Time Frame: Up to 6 Months following the procedure ]Freedom from clinically driven target lesion revascularization (CD-TLR) within 6 months.
- Composite clinical safety by freedom from adverse events including death, MALE, major unplanned amputation, or CD-TLR. [ Time Frame: Up to 6 Months following the procedure ]Freedom from composite of death within 30 days from the index procedure, MALE, major unplanned amputation or CD-TLR within 6 months.
- TVAL% change from post-procedure [ Time Frame: 6 Months following the 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
- Composite clinical safety by freedom from adverse events including death, unplanned amputation, CD-TLR, SAE or MALE. [ Time Frame: Up to 12 months following the procedure ]Freedom from composite of death, unplanned amputation and CD-TLR, serious adverse events (SAE) and MALE.
- Event-free survival [ Time Frame: 12 months following the procedure ]Proportion of patients reaching 12-month endpoint without a composite clinical safety event.
- QVA change from post-procedure [ Time Frame: 6 months following the procedure ]Improvement in % diameter stenosis (%DSS) of the target lesion (TL) and the maximum late lumen loss for the lesion (LLL) will be assessed by quantitative vascular angiography (QVA).
- IVUS change from post-procedure [ Time Frame: 6 months following the procedure ]Improvement in intravascular ultrasound (IVUS) result with in the TL (subgroup analysis).
- Amputation-free survival [ Time Frame: 30 days, 6 and 12 months following the procedure ]Percentage of patients reaching the endpoints without major or minor amputation.
- Major and minor amputations and amputation level [ Time Frame: 30 days, 6 and 12 months following the procedure ]Percentage of patients requiring amputation (major: above ankle, minor: below ankle), categorized by level on the foot, ankle, or leg.
- Change in foot wounds versus baseline [ Time Frame: 30 days, 6 and 12 Months following the procedure ]The number and total size of foot wounds, reduction in number and size of baseline wounds, and occurrence of new wounds (number and size) will be measured against baseline.
- Resolved CLI death [ Time Frame: 30 days, 6 and 12 months following the procedure ]The rate of deaths in patients who had a resolution of their critical limb ischemia (CLI).
- CD-TLR [ Time Frame: 30 days, 6 and 12 months following the procedure ]
- Primary sustained clinical improvement versus baseline [ Time Frame: 30 days, 6 and 12 months following the procedure ]Sustained upward shift of at least 1 category on Rutherford classification as compared to baseline without the need for repeated TLR or surgical revascularization in amputation-free surviving subjects.
- Secondary sustained clinical improvement versus baseline [ Time Frame: 30 days, 6 and 12 months following the procedure ]Sustained upward shift of at least 1 category on Rutherford classification as compared to baseline including the need for repeated TLR or surgical revascularization in amputation-free surviving subjects.
- SVS WIfI score versus baseline [ Time Frame: 30 days, 6 and 12 months following the procedure ]
- EQ5D versus baseline [ Time Frame: 30 days, 6 and 12 months following the procedure ]
- Walking capacity assessment versus baseline [ Time Frame: 30 days, 6 and 12 months following the procedure ]
- SAE/MALE assessment [ Time Frame: 30 days, 6 and 12 months following the procedure ]
- Inflammatory biomarker changes from baseline [ Time Frame: 24 hours and 30 days ]
- Healthcare economic analysis [ Time Frame: From baseline to 24 months ]An analysis of the economics associated with the care of patients, including number of hospital days throughout the study, return visits and hospitalizations, time from index procedure to required revascularization and number of index-lesion-related readmissions.
- Infustion technical success [ Time Frame: Intra-procedural ]The grade of distribution (A-F) around infusion sites will be used as a qualitative measure of technical success of adventitial delivery of the drug.
- Revascularization success [ Time Frame: Intra-procedural ]Establishment of antegrade flow with residual stenosis <30% by angiogram.

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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 failure to successfully treat and obtain a <30% residual stenosis
- Target lesion length is >25 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-target lesions) >25 cm
- Lesions revascularized during the index case but untreated by Bullfrog
- Use of alternative therapy, e.g. 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

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02479620
United States, Arkansas | |
Arkansas Heart Hospital | |
Little Rock, Arkansas, United States, 72211 | |
United States, Colorado | |
Denver Veterans Administration Hospital | |
Denver, Colorado, United States, 80220 | |
United States, Michigan | |
Mid-Michigan Heart & Vascular | |
Saginaw, Michigan, United States, 48604 | |
United States, Mississippi | |
Hattiesburg Clinic | |
Hattiesburg, Mississippi, United States, 39401 | |
United States, Missouri | |
St.Louis University Hospital | |
Saint Louis, Missouri, United States, 63110 | |
United States, New Jersey | |
Holy Name Medical Center | |
Teaneck, New Jersey, United States, 07666 | |
United States, North Carolina | |
UNC Health Care - Rex Hospital | |
Raleigh, North Carolina, United States, 27607 | |
United States, South Dakota | |
Sanford Research | |
Sioux Falls, South Dakota, United States, 57101 | |
United States, Tennessee | |
Tennova - Turkey Creek Medical Center | |
Knoxville, Tennessee, United States, 37934 | |
United States, Texas | |
Mission Research Institute (New Braunfels Cardiology - GRMC) | |
New Braunfels, Texas, United States, 78130 |
Principal Investigator: | George Adams, MD | REX Hospital, University of North Carolina Healthcare | |
Principal Investigator: | Donald Jacobs, MD | Saint Louis University Hospital |
Responsible Party: | Mercator MedSystems, Inc. |
ClinicalTrials.gov Identifier: | NCT02479620 |
Other Study ID Numbers: |
CIP0173 |
First Posted: | June 24, 2015 Key Record Dates |
Last Update Posted: | February 19, 2020 |
Last Verified: | February 2020 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | Yes |
Ischemia Pathologic Processes Dexamethasone Dexamethasone acetate Dexamethasone 21-phosphate BB 1101 Anti-Inflammatory Agents Antiemetics Autonomic Agents Peripheral Nervous System Agents |
Physiological Effects of Drugs Gastrointestinal Agents Glucocorticoids Hormones Hormones, Hormone Substitutes, and Hormone Antagonists Antineoplastic Agents, Hormonal Antineoplastic Agents Protease Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |