Critical Limb Ischemia Rapid Delivery by SurgWerks-CLI Kit and VXP System

NCT02538978 | Unknown Phase 3 DMC

• 1 other identifier: CST/CLI/143003
• Study Type: interventional
• Target: 224
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a prospective, double-blinded, randomized, placebo-controlled, multi-center, pivotal clinical study in which subjects are evaluated for prevention of major limb amputation in the treatment of non-reconstructable Rutherford Category 5 critical limb ischemia (CLI). Subjects will be randomized in 3:1 ratio (device treatment: placebo-control).

Conditions

Critical Limb Ischemia (CLI)

Keywords

CLI

Outcome Measures

Primary Outcomes (1)

• Major Limb Amputation Free Survival

  The measure of survival without a major (above the ankle) amputation within 12 months from the procedure and between group analyses at 12 months.

  12 months

Secondary Outcomes (12)

• Major amputation

  12 months

• All-Cause Mortality

  12 months

• Doubling of wound size

  12 months

• New full thickness lesion

  12 months

• Wound healing (photographic method of measuring area, depth, perimeter and volume of wounds)

  1, 3, 6 and 12 months

Other Outcomes (2)

• Ankle Brachial Index (ABI)

  1, 3, 6 and 12 months

• Rest Pain

  1, 3, 6 and 12 months

Study Arms (2)

Device Arm

EXPERIMENTAL

Device arm subjects will receive an intra-operative point of care aspiration, preparation and intramuscular injection of autologous bone marrow concentrate (aBMC) into the afflicted lower index limb.

Biological: Autologous Bone Marrow Concentrate (aBMC)

Placebo Arm

PLACEBO COMPARATOR

Placebo arm subjects will undergo an intra-operative point of care aspiration and preparation of bone marrow via the investigational device exactly as the Treatment Arm. However, instead of receiving the dosing with the aBMC device output, they will receive an intramuscular injection of diluted autologous peripheral blood into the afflicted lower index limb.

Biological: Placebo Control (diluted autologous peripheral blood)

Interventions

Autologous Bone Marrow Concentrate (aBMC) BIOLOGICAL

Aspirated bone marrow will be processed by centrifugation, separating out a concentrate (aBMC) comprising primarily white blood cells and platelets. These cells will be injected i.m. to loci determined by the operating physician using imaging and vascular flow criteria. Device: SurgWerks-CLI Kit Device: VXP System

Device Arm

Placebo Control (diluted autologous peripheral blood) BIOLOGICAL

Diluted peripheral blood prepared in a blinded fashion to resemble bone marrow will be injected intramuscularly per the same procedure used for the Experimental Device Arm.

Also known as: Diluted autologous peripheral blood

Placebo Arm

Eligibility Criteria

• Age: 40 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• IC 1 Male or Female of age ≥ 40 and ≤ 85 years.
• IC 2 Chronic CLI from atherosclerotic ischemic peripheral arterial disease (PAD) of a lower limb classified as Rutherford Category 5: (ischemic pain at rest and minor tissue loss with ulceration per IC 3).
• IC 4 A non-surgical candidate for revascularization as ruled by the investigator and confirmed by the BICR (single reader) and defined as: failure of all previous standard revascularization therapies /reconstruction attempts (at least two weeks prior to enrollment) no conduit suitable for bypass grafting, medical high risk that precludes bypass surgery, and diffuse multi-segment disease, or extensive infra-popliteal disease not amenable to endovascular therapy..
• IC 5 Ability to maintain compliance with tolerated medical management regimen for PAD that includes smoking cessation, and may include management of hyperlipidemia, diabetic management, antiplatelet therapy, statin therapy, ACE inhibitor therapy (or ARB therapy) and beta blocker therapy for control of blood pressure.
• IC 6 Willingness, ability and commitment to participate in baseline and follow-up evaluations for the full length of the study.
• IC 7 Poor lower extremity perfusion defined as an:
• ABI ≤ 0.6, or
• Foot/Ankle SPP ≤ 30 mmHg, or
• Ankle systolic pressure ≤ 60 mmHg or Toe pressure \<40 mmHg
• IC 8 Written informed consent.

You may not qualify if:

• EC1 Women who are pregnant, lactating or planning a pregnancy during the twelve (12) months of the follow-up period.
• EC2 Advanced CLI of the affected index limb classified in a category other than Rutherford 5.
• EC3 Advanced CLI in the opposing limb (non-index) with Rutherford category 6.
• EC4 Patients with aorta-iliac occlusive disease with \>50% stenosis
• EC5 Any prior amputation in the index limb beyond the toe(s) or digits or trans-metatarsal in the past four weeks.
• EC6 Ischemic wounds with systemic infectious symptoms (fever, hypotension, and/or positive blood cultures).
• EC7 Ischemic wounds having exposed tendon or bone.
• EC8 PT/INR \> 2.0 in the pre-admission baseline. If on warfarin, PT/INR which is not titrated to ≥ 2.0 prior to the treatment procedure.
• EC9 Ulcers above the ankle
• EC10 Subjects on renal dialysis or with end stage renal disease (Serum creatinine of ≥ 2.5 mg/dl or GFR ≤ 15 using CKD-EPI equation of National Kidney Foundation).
• EC11 Poorly controlled diabetes mellitus (HbA1c ≥ 10%)
• EC12 Anemia defined as a Hgb of ≤ 10mg/dl or a HCT ≤ 30%
• EC13 Any diagnosed immune-deficient status except well-controlled HIV infection (defined as HIV RNA qPCR ≤ 20 copies/mL).
• EC14 History of any neoplastic disease/cancer (other than basal cell carcinoma) in the previous three (3) years.
• EC15 Intolerance to heparin.

Sponsors & Collaborators

• Cesca Therapeutics, Inc.: lead

MeSH Terms

Conditions

Chronic Limb-Threatening Ischemia

Condition Hierarchy (Ancestors)

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

Study Officials

• Dalip Sethi, PhD

  Cesca Therapeutics, Inc.

  STUDY DIRECTOR

Central Study Contacts

Kenneth Harris

CONTACT

510-844-7000; kharris@cescatherapeutics.com

Jack P Douglas, PhD

CONTACT

510-844-7000; jdouglas@cescatherapeutics.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 18, 2015
• First Posted: September 2, 2015
• Study Start: January 1, 2017
• Primary Completion: December 1, 2018
• Study Completion: March 1, 2019
• Last Updated: July 28, 2016

Record last verified: 2016-07