ClinicalTrials.gov
ClinicalTrials.gov Menu

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

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02479555
Recruitment Status : Recruiting
First Posted : June 24, 2015
Last Update Posted : March 22, 2017
Sponsor:
Information provided by (Responsible Party):
Mercator MedSystems, Inc.

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).

Condition or disease Intervention/treatment Phase
Chronic Limb Ischemia Drug: Dexamethasone sodium phosphate injection, USP, 4 mg/mL Phase 2

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.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
Official Title: LIMBO-PTA: Lower-Limb Adventitial Infusion of DexaMethasone Via Bullfrog to Reduce Occurrence of Restenosis After Percutaneous Transluminal Angioplasty Revascularization
Study Start Date : January 2016
Estimated Primary Completion Date : August 2018
Estimated Study Completion Date : February 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Angioplasty

Arm Intervention/treatment
Active Comparator: 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.

Drug: 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.


No Intervention: 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.




Primary Outcome Measures :
  1. Freedom from MALE [ Time Frame: Up to 6 months following the procedure ]
    Freedom from major adverse limb event (MALE) within 6 months.

  2. 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.

  3. 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.

  4. 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.


Secondary Outcome Measures :
  1. 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.

  2. Event-free survival [ Time Frame: 12 months following the procedure ]
    Proportion of patients reaching 12-month endpoint without a composite clinical safety event.

  3. 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).

  4. IVUS change from post-procedure [ Time Frame: 6 months following the procedure ]
    Improvement in intravascular ultrasound (IVUS) result with in the TL (subgroup analysis).

  5. Amputation-free survival [ Time Frame: 30 days, 6 and 12 months post-procedure ]
    Percentage of patients reaching the endpoints without major or minor amputation.

  6. Major and minor amputations and amputation level [ Time Frame: 30 days, 6 and 12 months post-procedure ]
    Percentage of patients requiring amputation (major: above ankle, minor: below ankle), categorized by level on the foot, ankle, or leg.

  7. Change in foot wounds versus baseline [ Time Frame: 30 days, 6 and 12 months post-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.

  8. Resolved CLI death [ Time Frame: 30 days, 6 and 12 months post-procedure ]
    The rate of deaths in patients who had a resolution of their critical limb ischemia (CLI).

  9. CD-TLR [ Time Frame: 30 days, 6 and 12 months post-procedure ]
  10. Primary sustained clinical improvement versus baseline [ Time Frame: 30 days, 6 and 12 months post-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.

  11. Secondary sustained clinical improvement versus baseline [ Time Frame: 30 days, 6 and 12 months post-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.

  12. SVS WIfI score versus baseline [ Time Frame: 30 days, 6 and 12 months post-procedure ]
  13. EQ5D versus baseline [ Time Frame: 30 days, 6 and 12 months post-procedure ]
    Quality of life assessment.

  14. Walking capacity assessment versus baseline [ Time Frame: 30 days, 6 and 12 months post-procedure ]
  15. SAE/MALE assessment [ Time Frame: 30 days, 6 and 12 months post-procedure ]
  16. Inflammatory biomarker changes from baseline [ Time Frame: 24 hours and 30 days ]
  17. 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.

  18. Infusion 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.

  19. Revascularization success [ Time Frame: Intra-procedural ]
    Establishment of antegrade flow with residual stenosis <30% by angiogram.



Information from the National Library of Medicine

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
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

Information from the National Library of Medicine

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): NCT02479555


Contacts
Contact: Kristen L. Poole, PhD 510-564-7761 ext 818 kpoole@mercatormed.com

Locations
Germany
Universitäts-Herzzentrum Freiburg Bad Krozingen GmbH Recruiting
Bad Krozingen, Germany, 79189
Contact: Janine Liechke       janine.lieschke@vascuscience.com   
Principal Investigator: Thomas Zeller, MD         
Universitätsklinikum Leipzig AöR Recruiting
Leipzig, Germany, 04103
Contact: Janine Lieschke       janine.lieschke@vascuscience.com   
Principal Investigator: Dierk Schiert, MD         
Medinos Kliniken des Landkreiss Sonneberg GmbH Recruiting
Sonneberg, Germany, 96515
Contact: Janine Lieschke       janine.lieschke@vascuscience.com   
Principal Investigator: Marcus Thieme, MD         
Sponsors and Collaborators
Mercator MedSystems, Inc.
Investigators
Principal Investigator: Dierk Scheinert, MD University Hospital of Leipzig

Responsible Party: Mercator MedSystems, Inc.
ClinicalTrials.gov Identifier: NCT02479555     History of Changes
Other Study ID Numbers: CIP0169
First Posted: June 24, 2015    Key Record Dates
Last Update Posted: March 22, 2017
Last Verified: March 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
Ischemia
Pathologic Processes
Dexamethasone acetate
Dexamethasone
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