Critical Limb Ischemia (CLI)Phase 3CLIRST IIINCT02538978
Critical Limb Ischemia Rapid Delivery by SurgWerks-CLI Kit and VXP System
A Phase 3 study testing Autologous Bone Marrow Concentrate (aBMC) in people with Critical Limb Ischemia (CLI), run by Cesca Therapeutics, Inc..
Trial 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). Read more about this study
- Who is it for?
- Ages 40 to 85 years
- Conditions the study is for
- Critical Limb Ischemia (CLI)
- What is being tested?
- Autologous Bone Marrow Concentrate (aBMC)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 224 participants
- Where
- No sites listed yet
- Study dates
- Jan 2017to Mar 2019
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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 3 Ulcer of the toe(s) and/or foot (below the ankle) having a total tissue loss (full thickness) of at least 0.5 cm2 but no greater than 20 cm2 (0.5 cm2 ≤ wound area ≤ 20 cm2) or greater than 10 cm2 on the heel. Note: exposed tendon or bone is an exclusion, see EC 7
- 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.
Show all 11Show fewer
- 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.
Who cannot join
- 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).
Show all 25Show fewer
- 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.
- EC16 Contraindicated to CT angiography.
- EC17 Medical risk that precludes anesthesia, or ASA Class 5
- EC18 Receiving anti-angiogenic treatment
- EC19 History of any coronary revascularization within the previous one (1) month.
- EC20 History of a stroke within the previous six (6) months.
- EC21 Anticipated need for any immunosuppressive drugs (including glucocorticoids).
- EC22 Subjects with severe non-proliferative or proliferative retinopathy.
- EC23 Patients with active known alcohol or illicit drug abuse.
- EC24 Severe comorbidity (i.e. cardiac or pulmonary) or poor general physical/mental health that, in the opinion of the Investigator, will not allow the subject to be a suitable study candidate (i.e. other advanced disease processes, diminished mental capacity, substance abuse, shortened life expectancy (≤1 year), etc.).
- EC25 The patient is currently involved in another clinical study.
Trial locations and contacts
No sites are listed yet.
About this study
Official title: Safety and Effectiveness of the SurgWerksTM-CLI Kit and VXPTM System for the Rapid Intra-operative Aspiration, Preparation and Intramuscular Injection of Concentrated Autologous Bone Marrow Cells Into the Ischemic Index Limb of Rutherford Category 5 Non-Reconstructable Critical Limb Ischemia Patients
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).
Read the detailed description
Device arm subjects will receive an intra-operative point of care aspiration, preparation and intramuscular injection of autologous bone marrow cell concentrate (aBMC) into the afflicted lower index limb.
Bone marrow will be collected bilaterally from the patient's iliac crests using the SurgWerks-CLI Kit aspiration trocar under local anesthesia with mild to moderate sedation or general anesthesia, processed through the VXP System device to yield a rich cell and plasma concentrate ("aBMC"). Additionally, 10 mL of autologous peripheral blood will be aspirated for the placebo preparation.
The Treatment Arm will receive the aBMC, which will be intramuscularly injected at multiple mapped sites/angiosomes into the ischemic index limb using the SurgWerks-CLI Kit supplied Therapeutic Infusion Needles and standard hypodermic needles. The procedure will be performed in a surgical suite and will take approximately 1.5-2.0 hours to complete. The subjects will be observed for 24 hours following the procedure for observation and control as necessary of post-operative pain, bleeding, and infection.
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.
At pre-specified follow-up intervals, all subjects in each arm will be evaluated for:
- Major limb amputation free survival
- Time to Treatment Failure (TTF)
- Wound healing: Quantitative evaluation of wound(s)
- Quality of life assessment (VascuQoL and SF-36)
- Skin Perfusion Pressure (SPP) - Quantitative evaluation of blood flow
- Rest pain assessment
- Brachial Index (ABI)
- Conditions
- Critical Limb Ischemia (CLI)
- Being tested
- Autologous Bone Marrow Concentrate (aBMC), Placebo Control (diluted autologous peripheral blood)
- Keywords
- CLI
- Medical subject headings
- Chronic Limb-Threatening Ischemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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
Placebo Control (diluted autologous peripheral blood)Biological
Also called Diluted autologous peripheral blood
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Biological: Placebo Control (diluted autologous peripheral blood) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 12 months
Secondary outcomes (12)
Major amputation
Above the ankle amputation
Measured: 12 months
All-Cause Mortality
Death from any cause
Measured: 12 months
Doubling of wound size
Proportion of wounds that have doubled in size (area)
Measured: 12 months
New full thickness lesion
New full thickness lesion (>1 cm2) on the index limb.
Measured: 12 months
Wound healing (photographic method of measuring area, depth, perimeter and volume of wounds)
Quantitative evaluation of wound area continuous metric data (sq.cm.)
Measured: 1, 3, 6 and 12 months
Wound healing (photographic method of measuring area, depth, perimeter and volume of wounds)
Quantitative evaluation of wound depth and perimeter in continuous metric data (cm)
Measured: 1, 3, 6 and 12 months
Wound healing (photographic method of measuring area, depth, perimeter and volume of wounds)
Quantitative evaluation of wound volume in continuous metric data (cu.cm.)
Measured: 1, 3, 6 and 12 months
Quality of Life Assessment (a PAD-specific health-related quality of life instrument)
VascuQoL Questionnaire (using subjective, ordinal data regarding patient life style on a scale of 1-7, where 1="all of the time", and 7= "none of the time").
Measured: 1, 3, 6, and 12 months
Quality of Life Assessment (a PAD-specific health-related quality of life instrument)
VascuQoL Questionnaire (using subjective, ordinal data regarding patient discomfort on a scale of 1-7, where 1="A very great deal of discomfort or distress", and 7= "no discomfort or distress").
Measured: 1, 3, 6, and 12 months
Quality of Life Assessment (a PAD-specific health-related quality of life instrument)
VascuQoL Questionnaire (using subjective, ordinal data regarding activity on a scale of 1-7, where 1="Totally limited, couldn't go shopping at all", and 7= "not at all limited").
Measured: 1, 3, 6, and 12 months
Quality of Life Assessment (a PAD-specific health-related quality of life instrument)
VascuQoL Questionnaire (using subjective, ordinal data regarding walking improvement on a scale of 1-7, where 1="Not at all", and 7= "a very great deal").
Measured: 1, 3, 6, and 12 months
Skin Perfusion Pressure (SPP)
Limb pressure measurement as a proxy for tissue perfusion
Measured: 1, 3, 6 and 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Sep 2015 (estimated)
- Study startJan 2017
- Primary completionDec 2018 (estimated)
- Study completionMar 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Critical Limb Ischemia (CLI)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 224 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Cesca Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Dalip Sethi, PhD, Study director, Cesca Therapeutics, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02538978
- Sponsor's protocol ID
- CST/CLI/143003
- Acronym
- CLIRST III
- Status last verified
- Jul 2016
- First submitted
- 18 Aug 2015
- Last updated
- 28 Jul 2016
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 28 Jul 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Effectiveness of the SurgWerksTM-CLI Kit and VXPTM System for the Rapid Intra-operative Aspiration, Preparation and Intramuscular Injection of Concentrated Autologous Bone Marrow Cells Into the Ischemic Index Limb of Rutherford Category 5 Non-Reconstructable Critical Limb Ischemia Patients
- ClinicalTrials.gov ID
- NCT02538978
- Acronym / sponsor ID
- CLIRST III / CST/CLI/143003
- Conditions
- Critical Limb Ischemia (CLI)
- Keywords
- CLI
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 224 participants (estimated)
- Lead sponsor
- Cesca Therapeutics, Inc.Industry (pharma, biotech, devices)
- Study start
- Jan 2017
- Primary completion
- Dec 2018 (estimated)
- Study completion
- Mar 2019 (estimated)
- First posted
- 2 Sep 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
Device arm subjects will receive an intra-operative point of care aspiration, preparation and intramuscular injection of autologous bone marrow cell concentrate (aBMC) into the afflicted lower index limb.
Bone marrow will be collected bilaterally from the patient's iliac crests using the SurgWerks-CLI Kit aspiration trocar under local anesthesia with mild to moderate sedation or general anesthesia, processed through the VXP System device to yield a rich cell and plasma concentrate ("aBMC"). Additionally, 10 mL of autologous peripheral blood will be aspirated for the placebo preparation.
The Treatment Arm will receive the aBMC, which will be intramuscularly injected at multiple mapped sites/angiosomes into the ischemic index limb using the SurgWerks-CLI Kit supplied Therapeutic Infusion Needles and standard hypodermic needles. The procedure will be performed in a surgical suite and will take approximately 1.5-2.0 hours to complete. The subjects will be observed for 24 hours following the procedure for observation and control as necessary of post-operative pain, bleeding, and infection.
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.
At pre-specified follow-up intervals, all subjects in each arm will be evaluated for:
- Major limb amputation free survival
- Time to Treatment Failure (TTF)
- Wound healing: Quantitative evaluation of wound(s)
- Quality of life assessment (VascuQoL and SF-36)
- Skin Perfusion Pressure (SPP) - Quantitative evaluation of blood flow
- Rest pain assessment
- Brachial Index (ABI)
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Device Arm | Experimental | Biological: Autologous Bone Marrow Concentrate (aBMC)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. |
| Placebo Arm | Placebo comparator | Biological: Placebo Control (diluted autologous peripheral blood)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. |
Who may qualify
- Ages
- 40 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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 3 Ulcer of the toe(s) and/or foot (below the ankle) having a total tissue loss (full thickness) of at least 0.5 cm2 but no greater than 20 cm2 (0.5 cm2 ≤ wound area ≤ 20 cm2) or greater than 10 cm2 on the heel. Note: exposed tendon or bone is an exclusion, see EC 7
- 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.
Key exclusion criteria (25 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Autologous Bone Marrow Concentrate (aBMC)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 | Biological | Device Arm |
| Placebo Control (diluted autologous peripheral blood)Also: Diluted autologous peripheral bloodDiluted 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. | Biological | Placebo Arm |
Primary outcome
Major Limb Amputation Free Survival
Time frame: 12 months
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 secondary outcomes
Major amputation
Time frame: 12 months
All-Cause Mortality
Time frame: 12 months
Doubling of wound size
Time frame: 12 months
New full thickness lesion
Time frame: 12 months
Wound healing (photographic method of measuring area, depth, perimeter and volume of wounds)
Time frame: 1, 3, 6 and 12 months
Wound healing (photographic method of measuring area, depth, perimeter and volume of wounds)
Time frame: 1, 3, 6 and 12 months
Wound healing (photographic method of measuring area, depth, perimeter and volume of wounds)
Time frame: 1, 3, 6 and 12 months
Quality of Life Assessment (a PAD-specific health-related quality of life instrument)
Time frame: 1, 3, 6, and 12 months
Quality of Life Assessment (a PAD-specific health-related quality of life instrument)
Time frame: 1, 3, 6, and 12 months
Quality of Life Assessment (a PAD-specific health-related quality of life instrument)
Time frame: 1, 3, 6, and 12 months
Quality of Life Assessment (a PAD-specific health-related quality of life instrument)
Time frame: 1, 3, 6, and 12 months
Skin Perfusion Pressure (SPP)
Time frame: 1, 3, 6 and 12 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jul 2016.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dalip Sethi, PhD study director
Cesca Therapeutics, Inc.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Autologous Bone Marrow Concentrate (aBMC) in people with Critical Limb Ischemia (CLI), run by Cesca Therapeutics, Inc..
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 28 Jul 2016. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Kenneth Harris (510-844-7000, kharris@cescatherapeutics.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Major Limb Amputation Free Survival (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jul 2016.