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Temsirolimus Adventitial Delivery to Improve ANGioplasty and/or Atherectomy Revascularization Outcomes Below the Knee (TANGO-3)

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: NCT04433572
Recruitment Status : Not yet recruiting
First Posted : June 16, 2020
Last Update Posted : June 16, 2020
Sponsor:
Information provided by (Responsible Party):
Mercator MedSystems, Inc.

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.

Condition or disease Intervention/treatment Phase
Peripheral Artery Disease Critical Limb Ischemia Drug: Temsirolimus Drug: Saline placebo Phase 3

Detailed Description:
After completion of revascularization therapy and any decision to place stents, participants will be qualified for final enrollment in the study and will be randomized 1:1 and treated with the investigational drug or placebo. 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 400 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Block randomization will be stratified for Rutherford 3 and for Rutherford 4/5 participants such that each strata will be randomized 1:1. Block randomization will also be stratified by site such that each site will be assigned a 1:1 randomization.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:

The active vials and placebo vials will be identical in size, color and appearance on reconstitution. 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.

Primary Purpose: Treatment
Official Title: Temsirolimus Adventitial Delivery to Improve ANGioplasty and/or Atherectomy Revascularization Outcomes Below the Knee: 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
Estimated Study Start Date : December 1, 2020
Estimated Primary Completion Date : December 1, 2025
Estimated Study Completion Date : December 1, 2025


Arm Intervention/treatment
Active Comparator: Temsirolimus
Temsirolimus delivered to adventitia and perivascular tissue after primary revascularization
Drug: Temsirolimus
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.

Placebo Comparator: Placebo
Saline placebo delivered to adventitia and perivascular tissue after primary revascularization
Drug: Saline placebo
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.




Primary Outcome Measures :
  1. Freedom from Cinical Relevant Target Lesion Failure [ Time Frame: 6 Months ]

    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

  2. MALE + POD [ Time Frame: 30 Days ]
    Noninferiority of treatment vs. control groups in the composite freedom from Major Adverse Limb Event (MALE) in the target limb or Perioperative Death (POD)


Secondary Outcome Measures :
  1. Freedom from Target Lesion Failure [ Time Frame: 6 Months ]

    Superiority of treatment vs. control group in the composite freedom from the following:

    • Target Lesion Occlusion
    • Clinically Driven Target Lesion Revascularization
    • Ischemia-Driven Major Amputation of the target limb

  2. To determine non-inferiority in long-term mortality rate [ Time Frame: 12, 24, 36, 48, 60 months ]
    Death at the following time points

  3. To determine non-inferiority in freedom from all-cause death or major adverse limb event. [ Time Frame: 30 days, 6, 12 months ]
    Composite of all-cause death or MALE of the target limb

  4. To determine non-inferiority in amputation-free survival. [ Time Frame: 30 days, 6, 12, 24 months ]
    Freedom from death and ischemia-driven major amputation of the target limb

  5. 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). [ Time Frame: 30 days, 6, 12, 24 months ]

    AEs/ARs will be categorized into one of the following:

    • MALE of the target limb
    • Non-MALE target limb SAE/SAR
    • Other SAE/SAR
    • Non-serious AE/AR

    AEs/ARs will further be classified as:

    • Expected
    • UADE
    • SUSAR

    AEs/ARs will also be classified for relatedness (definitely, probably, possibly or not) to the following:

    • Revascularization procedure
    • Use of the Bullfrog device
    • The study drug

  6. Change of the individual components of the primary and secondary endpoints (ischemia-driven major amputation, clinically driven target lesion revascularization, clinically relevant target lesion occlusion or all target lesion occlusion) [ Time Frame: 6, 12, 24 months ]

    Taken individually:

    • Ischemia-driven major amputation of the target limb
    • CD-TLR
    • Clinically relevant target lesion occlusion
    • Any target lesion occlusion

  7. Freedom from major adverse limb events [ Time Frame: 30 days, 6, 12, 24 months ]
    MALE of the target limb

  8. Composite of the following wound healing measures [ Time Frame: 30 days, 6, 12 months ]
    • Total size of foot wounds on the target limb, percent and absolute change from baseline
    • Status of foot wounds on the target limb
    • Unassisted wound healing

  9. Reduction in unplanned minor amputations [ Time Frame: 30 days, 6, 12 months ]
    Unplanned minor amputation rate, overall and by level (forefoot, midfoot, hindfoot)

  10. Rutherford score improvement [ Time Frame: 30 days, 6, 12, 24 months ]
    Rutherford category and change from baseline

  11. WIfI score improvement [ Time Frame: 30 days, 6, 12, 24 months ]
    WIfI category and change from baseline

  12. Composite of hemodynamic improvement measures (ABI, TBI and toe pressure) [ Time Frame: 30 days, 6, 12, 24 months ]
    • Ankle-brachial index and change from baseline
    • Toe-brachial index and change from baseline
    • Toe pressure and change from baseline

  13. Patient reported quality of life benefits (VascuQoL) [ Time Frame: 30 days, 6, 12, 24 months ]
    VascuQoL results and change from baseline

  14. Patient reported outcomes (walking impairment questionnaire) benefits [ Time Frame: 30 days, 6, 12, 24 months ]
    WIQ results and change from baseline

  15. Primary and primary assisted patency rates [ Time Frame: 30 days, 6, 12, 24 months ]
    • Primary patency rate
    • Primary assisted patency rate

  16. Primary and secondary sustained clinical improvement rates [ Time Frame: 30 days, 6, 12, 24 months ]
    • Primary sustained clinical improvement rate
    • Secondary sustained clinical improvement rate



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.


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Ages Eligible for Study:   18 Years to 90 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  • Age ≥18 years and <90 years
  • Patient has documented severe claudication (Rutherford 3) or chronic Critical Limb Ischemia (CLI) (Rutherford 4-5) in the target limb due to arterial stenosis between the knee joint space and the ankle joint prior to the study procedure
  • Life expectancy >1 year in the Investigator's opinion
  • Patient has been informed of the nature of the study, agrees to participate, agrees to the follow-up schedule, and has signed an IRB approved consent form
  • Female patients 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 for one month preceding and 12 months following study treatment

Exclusion Criteria

  • Patient is already enrolled in another clinical study of systemic drug therapy or another device study that has not completed its primary endpoint, including prior enrollment in this study
  • Patient is unwilling or unlikely to comply with visit schedule
  • Patient is incapable of providing consent and/or incapable of understanding the nature, significance and implications of the clinical trial
  • Patient is already receiving or planned to receive systemic immunotherapy or chemotherapy
  • Patient is at high risk of thrombosis and taking systemic anticoagulant therapy that is unable to be withheld during the procedure
  • Patient has a CNS tumor or elevated risk for intracerebral bleeding and is receiving chronic anticoagulation therapy e.g. warfarin or oral anticoagulant (note: chronic antiplatelet therapy, e.g. aspirin and clopidogrel, and procedural anticoagulation therapy, e.g. heparin or bivalirudin, are allowed)
  • 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 performed within 14 days prior to the index procedure or planned within 30 days post index procedure is exclusionary; allowable exceptions to this exclusion include the following:

    1. concurrent procedures during the index procedure
    2. prior staged revascularization in the target limb, e.g. for inflow revascularization within 14 days of and prior to the index procedure
  • Planned major (above the ankle) target limb amputation
  • Active foot infection, including osteomyelitis of the metatarsal or more proximal region; allowable exceptions to this exclusion include the following:

    1. osteomyelitis in the toes
    2. mild cellulitis around the perimeter of gangrene
    3. small ulcers (<25mm largest diameter)
  • Inability to receive temsirolimus or iodinated contrast medium due to labeled contra-indications or known sensitivity reactions
  • Stage 3 (per SVS WIfI classification) or worse heel ulcers or heel ulcers that are determined to be primarily neuropathic in nature or non-ischemic in origin
  • Risk of amputation based on WIfI clinical staging = HIGH
  • Patient has active viral infection of SARS-CoV-2 or active disease diagnosis of COVID-19 (must be determined within 7 days of index procedure)
  • Patient has a bilirubin level of >1.5xULN
  • Estimated glomerular filtration rate (eGFR, calculated from serum creatinine using an isotope dilution mass spectrometry (IDMS)-traceable equation) less than 30 mL/min, except for patients with end stage renal disease on chronic hemodialysis

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): NCT04433572


Contacts
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Contact: Kirk Seward, PhD (510) 614-4555 kseward@mercatormed.com

Sponsors and Collaborators
Mercator MedSystems, Inc.
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Responsible Party: Mercator MedSystems, Inc.
ClinicalTrials.gov Identifier: NCT04433572    
Other Study ID Numbers: CIP0216
First Posted: June 16, 2020    Key Record Dates
Last Update Posted: June 16, 2020
Last Verified: June 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: No, there is not a plan to make individual participant data available to other researchers.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Peripheral Arterial Disease
Ischemia
Pathologic Processes
Atherosclerosis
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Cardiovascular Diseases
Peripheral Vascular Diseases
Sirolimus
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs