Temsirolimus Adventitial Delivery to Improve ANGioplasty and/or Atherectomy Revascularization Outcomes Below the Knee

NCT04433572 | Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: CIP0216
• Study Type: interventional
• Target: 250
• Locations: 1 country
• Sites: 2

Brief Summary

A multicenter, randomized, double-blind, placebo-controlled trial to evaluate the effect of Temsirolimus Perivascular Injection 0.1 mg/mL on the incidence of ischemia-driven major amputation, clinically driven target lesion revascularization, and clinically relevant target lesion occlusion after revascularization of lesions below the knee in patients with symptomatic Rutherford 3-5 peripheral artery disease. The primary safety endpoint will be gathered at 1-month post-index procedure. The primary efficacy endpoint will be gathered at 6 months post-index procedure. Participants will be followed for up to 5 years post-index procedure.

Conditions

Peripheral Artery Disease; Critical Limb Ischemia

Outcome Measures

Primary Outcomes (2)

• Freedom from Cinical Relevant Target Lesion Failure

  Superiority of treatment vs. control group in the composite freedom from the following: * Clinically Relevant Target Lesion Occlusion * Clinically Driven Target Lesion Revascularization * Ischemia-Driven Major Amputation of the Target Limb

  6 Months

• MALE + POD

  Noninferiority of treatment vs. control groups in the composite freedom from Major Adverse Limb Event (MALE) in the target limb or Perioperative Death (POD)

  30 Days

Secondary Outcomes (4)

• Rate of clinically relevant restenosis (CRR)

  6 months

• Freedom from target lesion failure (TLF)

  6 Months

• Freedom from clinically relevant target lesion failure (CR-TLF)

  12 Months

• Rate of clinically relevant restenosis (CRR)

  12 months

Other Outcomes (15)

• Safety and tolerability will be assessed from overall rate of adverse events (subclassified as major, serious, non-serious, unanticipated, revascularization procedure-related, device-related and drug-related).

  1, 6, 12, 24 months

• Freedom from target lesion failure metrics

  1, 6, 12 and 24 months

• Freedom from MALE of the index limb and all-cause death

  1, 6, 12, 24 months

Study Arms (2)

Temsirolimus

ACTIVE COMPARATOR

Temsirolimus delivered to adventitia and perivascular tissue after primary revascularization

Drug: Temsirolimus

Placebo

PLACEBO COMPARATOR

Saline placebo delivered to adventitia and perivascular tissue after primary revascularization

Drug: Saline placebo

Interventions

Temsirolimus DRUG

0.1 mg/mL temsirolimus, including contrast medium with approximately 75 mg iodine per mL. The dosage will be delivered in a volume of 0.50 mL per cm of target lesion length, up to 30 cm, with +50% allowance for anatomical considerations; for a total volume of up to 22.5 mL and a total dose of up to 2.25 mg in participants assigned to treatment. The same volumes of comparator agent will be delivered in control participants.

Temsirolimus

Saline placebo DRUG

Saline placebo, including contrast medium with approximately 75 mg iodine per mL. The dosage will be delivered in a volume of 0.50 mL per cm of target lesion length, up to 30 cm, with +50% allowance for anatomical considerations; for a total volume of up to 22.5 mL and a total dose of up to 2.25 mg in participants assigned to treatment. The same volumes of comparator agent will be delivered in control participants.

Placebo

Eligibility Criteria

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

You may qualify if:

• Pre-procedural:
• Participant has signed and dated informed consent, is capable of understanding the nature, significance and implications of the clinical trial, and is willing to comply with all study procedures and follow-up visits for the duration of the study.
• Participant is male or female, aged 18 years or older.
• If participant is female and of reproductive potential: agreement to use a highly effective contraception (abstinence is acceptable) for at least 90 days after study treatment.
• Participant has severe claudication (Rutherford 3) or chronic limb-threatening ischemia (CLTI) (Rutherford 4-5) in the Target Limb.
• Angiographic/Procedural:
• Participant has up to two de novo or restenotic Qualified Target Lesions meeting the following criteria, each based on the Investigator's visual assessment. Target Lesions should be considered separate if they are located in separate vessels (not in the same blood path) or have more than 10 cm intervening normal artery.
• Diameter
• ≥70% diameter stenosis anywhere within the Target Lesion or ≥50% diameter stenosis spanning at least 10 cm of length.
• Reference (normal) vessel diameter ≥2 mm and ≤8 mm. Location
• Any lesion chosen as a Target Lesion is in or spans at least one below-knee popliteal (P3 segment), tibial, or peroneal artery and is a culprit for dominant disease symptoms based on Investigator's assessment.
• ≥50% of the Target Lesion length is below the knee joint space (\<50% of Target Lesion length may extend above the midline of the knee joint space).
• ≥10 mm away from any previously placed stent or graft.
• A Target Lesion may cross an ostium of another artery (i.e. pass a bifurcation) but may only include one of the two branches. (Notes: Investigator should choose the dominant lesion for Target Lesion. Bifurcated lesions should be excluded, but if a lesion in a bifurcating vessel is separate from a Target Lesion based on intervening normal artery from which a proximal reference diameter can be measured, it may be treated as a second Target Lesion.) Length
• ≤30 cm in cumulative length from most proximal to most distal normal segment bounding the Target Lesion(s).

You may not qualify if:

• Pre-procedural:
• Participant is already enrolled in another clinical study of systemic or local vascular drug therapy or a vascular device study that has not completed its primary endpoint, including prior enrollment in this study.
• Participant is pregnant, nursing, or planning to become pregnant during the first 12 months after their enrollment in the study.
• Participant has presence of another anatomic or comorbid condition, or other medical, social, or psychological condition that, in the investigator's opinion, could limit the participant's ability to complete the clinical investigation or comply with follow-up requirements.
• Incapacitated individuals, defined as persons who are mentally ill, mentally handicapped, or individuals without legal authority, are excluded from the study population.
• Participant has a life expectancy of ≤1 year.
• Participant received in the prior 2 months, is currently receiving, or is planned to receive systemic immunosuppressive therapy, immunotherapy or chemotherapy.
• Participant has platelet count \< 100,000 cells per microliter or \> 700,000 cells per microliter, or hemoglobin \< 7.5 g/dL.
• Participant is unable to receive H1 antihistamine, temsirolimus or iodinated contrast medium due to labeled contra-indications or known sensitivity reactions except for contrast allergies for which adequate prophylaxis may be used.
• Participant has a CNS tumor.
• Participant has had a myocardial infarction within the 30 days prior to study procedure.
• Participant has had a cerebrovascular accident within the 90 days prior to the study procedure.
• Participant has had an intracerebral hemorrhage within the 1 year prior to the study procedure.
• Procedures performed during the same setting as the Index Procedure.
• Prior staged revascularization in the Target Limb but not the Target Lesion (e.g. for inflow revascularization) within the 30 days prior to the Index Procedure.

Sponsors & Collaborators

• Mercator MedSystems, Inc.: lead

Study Sites (2)

Cardiovascular Institute of the South

Houma, Louisiana, 70360, United States

RECRUITING

UT Southwestern

Dallas, Texas, 75235, United States

RECRUITING

MeSH Terms

Conditions

Peripheral Arterial Disease; Chronic Limb-Threatening Ischemia

Interventions

temsirolimus

Condition Hierarchy (Ancestors)

Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Peripheral Vascular Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Ischemia

Central Study Contacts

Kirk Seward, PhD

CONTACT

(510) 614-4555; kseward@mercatormed.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The active and placebo material provided to the operator in a blinded syringe or vial will be identical in size, color and appearance. Investigators and participants will be blinded to assignment. Any stents will be placed only after randomization, assignment, and adventitial drug therapy, although any stenting decisions (other than for treatment of AEs) must be made prior to randomization and adventitial drug delivery in order to avoid bias toward or against stenting. Participants will not be told of their treatment assignment until after they complete the trial.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Block randomization will be stratified for Rutherford 3 and for Rutherford 4/5 participants such that each strata will be randomized 2:1. Block randomization will also be stratified by site such that each site will be assigned a 2:1 randomization.

Study Record Dates

• First Submitted: June 9, 2020
• First Posted: June 16, 2020
• Study Start: July 30, 2025
• Primary Completion (Estimated): February 1, 2028
• Study Completion (Estimated): August 1, 2032
• Last Updated: August 5, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)