Temsirolimus Alone or Paired With Dexamethasone Delivered to the Adventitia to eNhance Clinical Efficacy After Femoropopliteal Revascularization

NCT03942601 | Terminated Phase 2 DMC FDA Drug

• 1 other identifier: CIP0215
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 11

Brief Summary

This is a prospective, multi-center, pilot feasibility study to document the effects of adventitial delivery of temsirolimus or temsirolimus with dexamethasone sodium phosphate injection, USP, after revascularization of femoropopliteal lesions in symptomatic patients with moderate to severe claudication (Rutherford 2-3) or critical limb ischemia (CLI) with rest pain (Rutherford 4). Subjects will be followed for up to 60 months post index procedure.

Conditions

Peripheral Arterial Disease

Outcome Measures

Primary Outcomes (3)

• Safety - Freedom from MALE-POD at 30 days

  Freedom from MALE-POD at 30 days

  30 days post intervention

• Effectiveness - Primary patency

  Primary patency (adjudicate by angio core lab)

  12 months post intervention

• Effectiveness - Freedom from CD-TLR

  Freedom from clinically driven target lesion revascularization (CD-TLR)) at 12 months.

  12 months post intervention

Study Arms (2)

Group 1 - temsirolimus injection

ACTIVE COMPARATOR

Temsirolimus Injection (0.4 mg/mL) and 20% contrast in Group 1

Drug: Temsirolimus

Group 2 - temsirolimus and dexamethasone injection

ACTIVE COMPARATOR

Temsirolimus Injection (0.4 mg/mL), Dexamethasone Sodium Phosphate Injection, USP (3.2 mg/mL) and 20% contrast in Group 2

Drug: Temsirolimus and dexamethasone sodium phosphate

Interventions

Temsirolimus DRUG

Temsirolimus Injection (0.4 mg/mL) and 20% contrast in Group 1

Group 1 - temsirolimus injection

Temsirolimus and dexamethasone sodium phosphate DRUG

Temsirolimus Injection (0.4 mg/mL), Dexamethasone Sodium Phosphate Injection, USP (3.2 mg/mL) and 20% contrast in Group 2

Group 2 - temsirolimus and dexamethasone injection

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

Inclusion Screening Criteria: * Age ≥18 years and ≤85 years at study enrollment * Subject has been informed of the nature of the study, agrees to participate and has signed an IRB-approved consent form * Subject is ambulatory * Female subjects of childbearing potential have a negative pregnancy test ≤7 days before the procedure and are willing to use a highly effective method of birth control (See Section 12.2) for one month preceding and 12 months following study treatment * Subject has documented moderate to severe claudication (Rutherford 2-3) or Critical Limb Ischemia (CLI) with rest pain (Rutherford 4) in the target limb due to arterial stenosis within the superficial femoral and/or popliteal artery * Life expectancy \>2 years in the Investigator's opinion Angiographic Criteria (Target Lesion Definition) * Target vessel reference diameter ≥3 mm and ≤8 mm * Single or multiple de novo atherosclerotic or restenotic lesion(s) with ≥70% narrowing in the superficial femoral or popliteal artery meeting the following criteria: * The target lesion must be ≤20 cm in total length * The target lesion does not have more than 5 cm of contiguous length of intervening normal artery * The target lesion does not cross into the common femoral artery or tibeoperoneal trunk * The target lesion is located at least 10 mm away from any previously placed stent or graft * Successful wire crossing (sub-intimal is allowed) and revascularization by balloon angioplasty of the target lesion with less than 30% residual stenosis and run-off in at least one patent vessel into the foot Exclusion Screening Criteria: * Subject is already enrolled in another clinical study of systemic drug therapy or another device study that has not completed its primary endpoint * Subject unwilling or unlikely to comply with visit schedule * Subjects who are incapable of providing consent and/or incapable of understanding the nature, significance and implications of the clinical trial * Subject is already receiving, has received in prior 2 months, or is planned in the 6 months after index procedure to receive systemic immunotherapy, chemotherapy, or systemic steroids (however, steroid pre-treatment for contrast allergy, inhaled steroids for asthma treatment or topical steroid uses are allowed) * Subject is receiving chronic anticoagulation therapy e.g. warfarin (note: chronic antiplatelet therapy, e.g. aspirin and clopidigrel, and procedural anticoagulation therapy, e.g. heparin or bivalirudin, are allowed) * Subject has a bilirubin level of \>1.5xULN * Recent (\<30 days prior to study procedure) myocardial infarction * Cerebrovascular accident \<60 days prior to the study procedure or any history of intracerebral hemorrhage * Any surgical or endovascular procedure (not including staged revascularization in the target limb, e.g. inflow revascularization prior to index procedure or below-knee revascularization after the index procedure) performed within 14 days prior to the index procedure or planned within 30 days post index procedure * Planned amputation in the target limb * Active foot infection or ischemic foot wound * Inability to receive temsirolimus, dexamethasone or iodinated contrast medium due to labeled contra-indications or known sensitivity reactions * Estimated glomerular filtration rate (eGFR, calculated from serum creatinine using an isotope dilution mass spectrometry (IDMS)-traceable equation) less than 30 mL/min Angiographic/Procedural Criteria * Hemodynamically significant inflow lesion (≥50% DS) or occlusion in the ipsilateral iliac artery in which there is failure to successfully treat and obtain a \<30% residual stenosis post-revascularization, with bailout stenting as needed (in-flow lesions should be treated prior to treating the target lesion) * Prior stent placement in target lesion (i.e., in-stent restenosis) * Target lesion restenosis of any kind within 6 months of a prior intervention * Use of alternative therapy, e.g. radiation therapy, drug-eluting stents (DES) or drug-eluting balloon/drug-coated balloons (DEB/DCB) as part of the target lesion treatment during the index procedure or during the previous 12 months * Use of atherectomy devices in the target lesion during the index procedure * Aneurysm in the target vessel * Acute thrombus in the target limb * Heavy eccentric or concentric calcification at target lesion, which in the judgment of the investigator would prevent penetration of the Micro-Infusion Device needle through the vessel wall

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Mercator MedSystems, Inc.: lead

Study Sites (11)

Arkansas Heart Hospital

Little Rock, Arkansas, 72211, United States

Location

St. Joseph Hospital of Orange Heart and Vascular Center

Orange, California, 92868, United States

Location

San Francisco VA Medical Center

San Francisco, California, 94121, United States

Location

University of Colorado

Denver, Colorado, 80045, United States

Location

Rocky Mountain Veterans Administration Hospital

Denver, Colorado, 80220, United States

Location

Advocate Christ Medical Center

Oak Lawn, Illinois, 60453, United States

Location

Columbia University Medical Center/NYPH

New York, New York, 10032, United States

Location

North Carolina Heart and Vascular

Raleigh, North Carolina, 27607, United States

Location

University Hospital

Cleveland, Ohio, 44106, United States

Location

Einstein Medical Center

Philadelphia, Pennsylvania, 19141, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Peripheral Arterial Disease

Interventions

temsirolimus; dexamethasone 21-phosphate

Condition Hierarchy (Ancestors)

Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Peripheral Vascular Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is an open-label study without randomization. Cohorts will be enrolled sequentially, with Group 1 followed by Group 2. Study Drug: Temsirolimus Injection (0.4 mg/mL) and 20% contrast in Group 1 or Temsirolimus Injection (0.4 mg/mL), Dexamethasone Sodium Phosphate Injection, USP (3.2 mg/mL) and 20% contrast in Group 2 Route of Administration: Bullfrog Micro-Infusion Device adventitial delivery Dosage Volume:0.5 mL per cm of target vessel length Up to 30 subjects in Group 1 and up to 30 subjects in Group 2. The study shall enroll subjects from up to 20 sites in the United States.

Study Record Dates

• First Submitted: May 6, 2019
• First Posted: May 8, 2019
• Study Start: October 1, 2019
• Primary Completion: April 30, 2021
• Study Completion: April 30, 2021
• Last Updated: July 10, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (11)