Critical Limb IschemiaNCT04255004
Autologous Peripheral Blood Mononuclear Cells in Diabetic Foot Patients With No-option Critical Limb Ischemia
A study testing Pall Celeris System, point of care device for human cell therapy in people with Critical Limb Ischemia and Diabetic Foot, run by Ospedale San Donato.
Trial summary
The objective of this trial is to determine whether PBMNCs in diabetic patients with critical, non revascularizable limb ischemia can prevent major amputation and affect mortality and healing. Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Critical Limb Ischemia, Diabetic Foot
- What is being tested?
- Pall Celeris System, point of care device for human cell therapy
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 76 participants
- Where
- No sites listed yet
- Study dates
- Jan 2014to Dec 2019
- Phase
- Interventional
- 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 18 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- ulcers with inadequate perfusion, as indicated by a transcutaneous oxygen pressure value (TcpO2) <30 mmHg;
- ulcers with grade I or II or III and stage C as defined by the Texas University Classification System or W1,2,3 - I 3 - FI 0,1 as defined by the WiFI Classification System
- not eligible for angioplasty or vascular surgery or following failed revascularization;
- possibility to save foot support.
Who cannot join
- lesion site above the tibial-tarsal joint;
- moderate or severe infection according by the WiFI classification system;
- NYHA class IV; d) Anemia (Hb<8g/dl);
- coagulation disorder/thrombocytopenia (PLT< 50,000 per microliter);
- active cancer/leukemia or lymphoma hematological disease.
About this study
Official title: Autologous Peripheral Blood Mononuclear Cells for Limb Salvage in Diabetic Foot Patients With No-option Critical Limb Ischemia
The objective of this trial is to determine whether PBMNCs in diabetic patients with critical, non revascularizable limb ischemia can prevent major amputation and affect mortality and healing.
Read the detailed description
This is an interventional study with historical control group carried out to assess as primary outcome major amputations, overall mortality, number of healed patients in group of patients who received repetitive intra-muscular implant of PBMNCs (3 times; 4-week interval) in comparison to a historical internal control group with a 1:1 case-control ratio. Secondary outcomes are TCPO2, healing time and rest pain.
No-option critical limb ischaemia is defined by evidence of no run-off pedal vessels, failure after several percutaneous intervention and no longer possible re-intervention, failure after infra-genicular bypass grafting, no-walking capacity with severe comorbidities unfit for surgical or endovascular procedures.
Inclusion criteria are: a) ulcers with inadequate perfusion, as indicated by a transcutaneous oxygen pressure value (TcpO2) <30 mmHg; b) ulcers with grade I or II or III and stage C as defined by the Texas University Classification System or W1,2,3 - I 3 - FI 0,1 as defined by the WiFI Classification System c) not eligible for angioplasty or vascular surgery or following failed revascularization; d) possibility to save foot support.
Exclusion criteria are: a) lesion site above the tibial-tarsal joint; b) moderate or severe infection according by the WiFI classification system; c) NYHA class IV; d) Anemia (Hb<8g/dl); e) coagulation disorder/thrombocytopenia (PLT< 50,000 per microliter); f) active cancer/leukemia or lymphoma hematological disease.
Standard of care in both groups includes: diabetes control maximization by the diabetologist, comprehensive foot assessment by the nurse together with the diabetologist, including determination of vibration perception threshold, 10-g monofilament test and TcpO2 measurement, dressings, off-loading and systemic therapy according to the IWGDF guidelines .
Informed consent for participation in the study during the progress of the clinical trial is obtained from all subjects.
Concentration of PB-MNCs autologous cell therapy is produced by a filtration-based point-of-care device with the intended for use intra-operatively, from 120 mL of anticoagulated blood. All the procedures are performed in operatory room with anaesthesiologic support (propofol and/or peripheral block). Blood withdrawal (120 ml) is collected through a peripheral venous access, than loaded and gravity filtration is allowed in about 10 minutes. During filtration, MNCs are captured in the filter while plasma, platelets (PLTs) and red blood cells (RBCs) are not retained. After appropriate surgical debridement of the wound bed multiple perilesional and intramuscular injections of PBMNC cells suspension (0.2-0.3cc in boluses) are injected along the relevant axis below the knee, at intervals of 1-2 cm and to a mean depth of 1.5-2 cm, using a 21G needle. This procedure is repeated on each patient for three times, at intervals of 30-45 days from each other.
Foot-sparing surgery, the removal of all the unviable tissue and the reconstruction of the foot to allow a functional deambulation,is performed at the same time of the last implant in the patients with increased TcpO2 value above 30 mmHg. Between the implants, diabetologists together with nurses evaluated changing in pain, infection signs, wound size, demarcation of the necrosis, granulation tissue formation, perilesional tissue trophism and TcpO2 value to optimize standard of care. After the first treatment, a two years follow-up is registered, with evaluation at 1-3-6-12-18-24 months.
A baseline assessment is carried out, in order to estimate any differences among cases and controls before the treatment. Statistical evaluation includes non-parametric tests (Mann-Whitney U test for independent samples for continuous variables and Cochrane chi-square test for discrete variables), evaluation of Relative Risk (RR), Absolute Risk Reduction (ARR), Relative Risk Reduction (RRR) and Number Needed to Treat (NNT), multivariate survival analysis (Kaplan-Meier's survival analysis model).
- Conditions
- Critical Limb Ischemia, Diabetic Foot
- Being tested
- Pall Celeris System, point of care device for human cell therapy
- Keywords
- autologous peripheral blood mononuclear cell, diabetic foot
- Medical subject headings
- Chronic Limb-Threatening Ischemia, Diabetic Foot
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pall Celeris System, point of care device for human cell therapyDevice
Concentration of PB-MNCs autologous cell therapy was produced by a filtration-based point-of-care device. All the procedures were performed in operatory room with anaesthesiologic support (propofol and/or peripheral block). Blood withdrawal (120 ml) was collected through a peripheral venous access. Blood was loaded, and gravity filtration was allowed to proceed until the upstream side of the filter had no remaining blood; filtration last about 10 minutes. During filtration, MNCs were captured in the filter while plasma, platelets (PLTs) and red blood cells (RBCs) were not retained. Immediately concentrate solution is injected in the perilesional area and intramuscular in the foot and the leg (0.2-0.3cc in boluses) below the knee, at intervals of 1-2 cm and to a mean depth of 1.5-2 cm, using a 21G needle. This procedure is repeated on each patient for three times, at intervals of 30-45 days from each other.
| Study group | Role | What they receive |
|---|---|---|
| A-PBMNC therapy | Active comparator | Patients in A-PBMNC therapy are treated with wound bed multiple perilesional and intramuscular injections of PBMNC cells suspension (0.2-0.3cc in boluses). This procedure is repeated on each patient for three times, at intervals of 30-45 days from each other. Receives: Device: Pall Celeris System, point of care device for human cell therapy |
| No A-PBMNC therapy | No intervention | Patients in No A-PBMNC therapy receive only supportive treatment including wound care and pain killer drug. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Amputation-free survival at 1 month
rate of non amputated limb 1 month after the intervention
Measured: 1 month
Amputation-free survival at 3 months
rate of non amputated limb 3 months after the intervention
Measured: 3 months
Amputation-free survival at 6 months
rate of non amputated limb 6 months after the intervention
Measured: 6 months
Amputation-free survival at 12 months
rate of non amputated limb 12 months after the intervention
Measured: 12 months
Amputation-free survival at 18 months
rate of non amputated limb 18 months after the intervention
Measured: 18 months
Amputation-free survival at 24 months
rate of non amputated limb 24 months after the intervention
Measured: 24 months
risk of death at 1 month
rate of dead subjects 1 month after the intervention
Measured: 1 month
risk of death at 3 months
rate of dead subjects 3 months after the intervention
Measured: 3 months
risk of death at 6 months
rate of dead subjects 6 months after the intervention
Measured: 6 months
risk of death at 12 months
rate of dead subjects 12 months after the intervention
Measured: 12 months
risk of death at 18 months
rate of dead subjects 18 months after the intervention
Measured: 18 months
risk of death at 24 months
rate of dead subjects 24 months after the intervention
Measured: 24 months
probability of healing at 1 month
rate of healed subjects 1 month after the intervention
Measured: 1 month
probability of healing at 3 months
rate of healed subjects 3 months after the intervention
Measured: 3 months
probability of healing at 6 months
rate of healed subjects 6 months after the intervention
Measured: 6 months
probability of healing at 12 months
rate of healed subjects 12 months after the intervention
Measured: 12 months
probability of healing at 18 months
rate of healed subjects 18 months after the intervention
Measured: 18 months
probability of healing at 24 months
rate of healed subjects 24 months after the intervention
Measured: 24 months
Secondary outcomes (3)
transcutaneous oxygen measurement (TcPO2) variation
comparison of TcPO2 at the second follow up (3 months after intervention) with the baseline measure
Measured: 0-3 months
Healing time
time to reach complete epithelialization
Measured: within 24 months
rest pain
comparison of rest pain measured by a numeric rating scale (NRS) min 0 - max 10, where 10 is the worst pain the patient has felt
Measured: 0-1-3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Feb 2020
- Study startJan 2014
- Primary completionFeb 2019
- Study completionDec 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (42)Papers the sponsor has linked to this study.
- Other trials for Critical Limb IschemiaStudies 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 N/A
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- We would enroll a cohort of 38 consecutive diabetic patients with CLI in charge at the Diabetic Foot Unit of the San Donato Hospital in Arezzo or referred from other Italian hospitals, who have no option for revascularization or are not further eligible for revascularization according to ESVS ESC 2017 criteria to undergo PB-MNC implantation. Furthermore, an historical control group, with a 1:1 case-control ratio, will be collected backwards from our records, when PBMNCs cellular therapy was not available in our center, with same no-option CLI diagnosis.
- Masking
- None (open label)
- Enrolment
- 76 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ospedale San Donato
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Alessia Scatena, Ospedale San Donato
- Investigators
- Leonardo Ercolini, MD, Study chair, Vascular Surgery Unit San Donato Hospital Arezzo
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04255004
- Sponsor's protocol ID
- MONODIAB-19-01
- Status last verified
- Jan 2020
- First submitted
- 25 Jan 2020
- Last updated
- 5 Feb 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: data should not be shared before study completion and approvation by all the collaborators. Sharing data before this time would jeopardize the integrity of the clinical trial process and risk the scientific validity of the results.
Publications
Abu Dabrh AM, Steffen MW, Undavalli C, Asi N, Wang Z, Elamin MB, Conte MS, Murad MH. The natural history of untreated severe or critical limb ischemia. J Vasc Surg. 2015 Dec;62(6):1642-51.e3. doi: 10.1016/j.jvs.2015.07.065. Epub 2015 Sep 26.
PubMed 26391460Golomb BA, Dang TT, Criqui MH. Peripheral arterial disease: morbidity and mortality implications. Circulation. 2006 Aug 15;114(7):688-99. doi: 10.1161/CIRCULATIONAHA.105.593442. No abstract available.
PubMed 16908785Rigato M, Monami M, Fadini GP. Autologous Cell Therapy for Peripheral Arterial Disease: Systematic Review and Meta-Analysis of Randomized, Nonrandomized, and Noncontrolled Studies. Circ Res. 2017 Apr 14;120(8):1326-1340. doi: 10.1161/CIRCRESAHA.116.309045. Epub 2017 Jan 17.
PubMed 28096194Fantin A, Vieira JM, Gestri G, Denti L, Schwarz Q, Prykhozhij S, Peri F, Wilson SW, Ruhrberg C. Tissue macrophages act as cellular chaperones for vascular anastomosis downstream of VEGF-mediated endothelial tip cell induction. Blood. 2010 Aug 5;116(5):829-40. doi: 10.1182/blood-2009-12-257832. Epub 2010 Apr 19.
PubMed 20404134Baer C, Squadrito ML, Iruela-Arispe ML, De Palma M. Reciprocal interactions between endothelial cells and macrophages in angiogenic vascular niches. Exp Cell Res. 2013 Jul 1;319(11):1626-34. doi: 10.1016/j.yexcr.2013.03.026. Epub 2013 Mar 28.
PubMed 23542777Wynn TA, Vannella KM. Macrophages in Tissue Repair, Regeneration, and Fibrosis. Immunity. 2016 Mar 15;44(3):450-462. doi: 10.1016/j.immuni.2016.02.015.
PubMed 26982353Krzyszczyk P, Schloss R, Palmer A, Berthiaume F. The Role of Macrophages in Acute and Chronic Wound Healing and Interventions to Promote Pro-wound Healing Phenotypes. Front Physiol. 2018 May 1;9:419. doi: 10.3389/fphys.2018.00419. eCollection 2018.
PubMed 29765329Awad O, Dedkov EI, Jiao C, Bloomer S, Tomanek RJ, Schatteman GC. Differential healing activities of CD34+ and CD14+ endothelial cell progenitors. Arterioscler Thromb Vasc Biol. 2006 Apr;26(4):758-64. doi: 10.1161/01.ATV.0000203513.29227.6f. Epub 2006 Jan 12.
PubMed 16410458Jarajapu YP, Hazra S, Segal M, Li Calzi S, Jadhao C, Qian K, Mitter SK, Raizada MK, Boulton ME, Grant MB. Vasoreparative dysfunction of CD34+ cells in diabetic individuals involves hypoxic desensitization and impaired autocrine/paracrine mechanisms. PLoS One. 2014 Apr 8;9(4):e93965. doi: 10.1371/journal.pone.0093965. eCollection 2014.
PubMed 24713821Spaltro G, Straino S, Gambini E, Bassetti B, Persico L, Zoli S, Zanobini M, Capogrossi MC, Spirito R, Quarti C, Pompilio G. Characterization of the Pall Celeris system as a point-of-care device for therapeutic angiogenesis. Cytotherapy. 2015 Sep;17(9):1302-13. doi: 10.1016/j.jcyt.2015.04.006. Epub 2015 May 30.
PubMed 26038175Moriya J, Minamino T, Tateno K, Shimizu N, Kuwabara Y, Sato Y, Saito Y, Komuro I. Long-term outcome of therapeutic neovascularization using peripheral blood mononuclear cells for limb ischemia. Circ Cardiovasc Interv. 2009 Jun;2(3):245-54. doi: 10.1161/CIRCINTERVENTIONS.108.799361. Epub 2009 Mar 30.
PubMed 20031722Persiani F, Paolini A, Camilli D, Mascellari L, Platone A, Magenta A, Furgiuele S. Peripheral Blood Mononuclear Cells Therapy for Treatment of Lower Limb Ischemia in Diabetic Patients: A Single-Center Experience. Ann Vasc Surg. 2018 Nov;53:190-196. doi: 10.1016/j.avsg.2018.05.036. Epub 2018 Jul 25.
PubMed 30053546Armstrong DG, Lavery LA, Harkless LB. Validation of a diabetic wound classification system. The contribution of depth, infection, and ischemia to risk of amputation. Diabetes Care. 1998 May;21(5):855-9. doi: 10.2337/diacare.21.5.855.
PubMed 9589255Wagner FW Jr. The dysvascular foot: a system for diagnosis and treatment. Foot Ankle. 1981 Sep;2(2):64-122. doi: 10.1177/107110078100200202. No abstract available.
PubMed 7319435Lipsky BA, Aragon-Sanchez J, Diggle M, Embil J, Kono S, Lavery L, Senneville E, Urbancic-Rovan V, Van Asten S; International Working Group on the Diabetic Foot; Peters EJ. IWGDF guidance on the diagnosis and management of foot infections in persons with diabetes. Diabetes Metab Res Rev. 2016 Jan;32 Suppl 1:45-74. doi: 10.1002/dmrr.2699. No abstract available.
PubMed 26386266
Study at a glance
From the registry record, last updated by the sponsor on 5 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Autologous Peripheral Blood Mononuclear Cells for Limb Salvage in Diabetic Foot Patients With No-option Critical Limb Ischemia
- ClinicalTrials.gov ID
- NCT04255004
- Acronym / sponsor ID
- MONODIAB-19-01
- Conditions
- Critical Limb Ischemia, Diabetic Foot
- Keywords
- autologous peripheral blood mononuclear cell, diabetic foot
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 76 participants (actual)
- Lead sponsor
- Ospedale San DonatoUniversity, hospital or other
- Study start
- Jan 2014 (actual)
- Primary completion
- Feb 2019 (actual)
- Study completion
- Dec 2019 (actual)
- First posted
- 5 Feb 2020 (actual)
- 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.
The objective of this trial is to determine whether PBMNCs in diabetic patients with critical, non revascularizable limb ischemia can prevent major amputation and affect mortality and healing.
Detailed description
This is an interventional study with historical control group carried out to assess as primary outcome major amputations, overall mortality, number of healed patients in group of patients who received repetitive intra-muscular implant of PBMNCs (3 times; 4-week interval) in comparison to a historical internal control group with a 1:1 case-control ratio. Secondary outcomes are TCPO2, healing time and rest pain.
No-option critical limb ischaemia is defined by evidence of no run-off pedal vessels, failure after several percutaneous intervention and no longer possible re-intervention, failure after infra-genicular bypass grafting, no-walking capacity with severe comorbidities unfit for surgical or endovascular procedures.
Inclusion criteria are: a) ulcers with inadequate perfusion, as indicated by a transcutaneous oxygen pressure value (TcpO2) <30 mmHg; b) ulcers with grade I or II or III and stage C as defined by the Texas University Classification System or W1,2,3 - I 3 - FI 0,1 as defined by the WiFI Classification System c) not eligible for angioplasty or vascular surgery or following failed revascularization; d) possibility to save foot support.
Exclusion criteria are: a) lesion site above the tibial-tarsal joint; b) moderate or severe infection according by the WiFI classification system; c) NYHA class IV; d) Anemia (Hb<8g/dl); e) coagulation disorder/thrombocytopenia (PLT< 50,000 per microliter); f) active cancer/leukemia or lymphoma hematological disease.
Standard of care in both groups includes: diabetes control maximization by the diabetologist, comprehensive foot assessment by the nurse together with the diabetologist, including determination of vibration perception threshold, 10-g monofilament test and TcpO2 measurement, dressings, off-loading and systemic therapy according to the IWGDF guidelines .
Informed consent for participation in the study during the progress of the clinical trial is obtained from all subjects.
Concentration of PB-MNCs autologous cell therapy is produced by a filtration-based point-of-care device with the intended for use intra-operatively, from 120 mL of anticoagulated blood. All the procedures are performed in operatory room with anaesthesiologic support (propofol and/or peripheral block). Blood withdrawal (120 ml) is collected through a peripheral venous access, than loaded and gravity filtration is allowed in about 10 minutes. During filtration, MNCs are captured in the filter while plasma, platelets (PLTs) and red blood cells (RBCs) are not retained. After appropriate surgical debridement of the wound bed multiple perilesional and intramuscular injections of PBMNC cells suspension (0.2-0.3cc in boluses) are injected along the relevant axis below the knee, at intervals of 1-2 cm and to a mean depth of 1.5-2 cm, using a 21G needle. This procedure is repeated on each patient for three times, at intervals of 30-45 days from each other.
Foot-sparing surgery, the removal of all the unviable tissue and the reconstruction of the foot to allow a functional deambulation,is performed at the same time of the last implant in the patients with increased TcpO2 value above 30 mmHg. Between the implants, diabetologists together with nurses evaluated changing in pain, infection signs, wound size, demarcation of the necrosis, granulation tissue formation, perilesional tissue trophism and TcpO2 value to optimize standard of care. After the first treatment, a two years follow-up is registered, with evaluation at 1-3-6-12-18-24 months.
A baseline assessment is carried out, in order to estimate any differences among cases and controls before the treatment. Statistical evaluation includes non-parametric tests (Mann-Whitney U test for independent samples for continuous variables and Cochrane chi-square test for discrete variables), evaluation of Relative Risk (RR), Absolute Risk Reduction (ARR), Relative Risk Reduction (RRR) and Number Needed to Treat (NNT), multivariate survival analysis (Kaplan-Meier's survival analysis model).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- We would enroll a cohort of 38 consecutive diabetic patients with CLI in charge at the Diabetic Foot Unit of the San Donato Hospital in Arezzo or referred from other Italian hospitals, who have no option for revascularization or are not further eligible for revascularization according to ESVS ESC 2017 criteria to undergo PB-MNC implantation. Furthermore, an historical control group, with a 1:1 case-control ratio, will be collected backwards from our records, when PBMNCs cellular therapy was not available in our center, with same no-option CLI diagnosis.
| Arm | Type | Receives |
|---|---|---|
| A-PBMNC therapy | Active comparator | Device: Pall Celeris System, point of care device for human cell therapyPatients in A-PBMNC therapy are treated with wound bed multiple perilesional and intramuscular injections of PBMNC cells suspension (0.2-0.3cc in boluses). This procedure is repeated on each patient for three times, at intervals of 30-45 days from each other. |
| No A-PBMNC therapy | No intervention | –Patients in No A-PBMNC therapy receive only supportive treatment including wound care and pain killer drug. |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- ulcers with inadequate perfusion, as indicated by a transcutaneous oxygen pressure value (TcpO2) <30 mmHg;
- ulcers with grade I or II or III and stage C as defined by the Texas University Classification System or W1,2,3 - I 3 - FI 0,1 as defined by the WiFI Classification System
- not eligible for angioplasty or vascular surgery or following failed revascularization;
- possibility to save foot support.
Key exclusion criteria (5 listed)
- lesion site above the tibial-tarsal joint;
- moderate or severe infection according by the WiFI classification system;
- NYHA class IV; d) Anemia (Hb<8g/dl);
- coagulation disorder/thrombocytopenia (PLT< 50,000 per microliter);
- active cancer/leukemia or lymphoma hematological disease.
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 |
|---|---|---|
| Pall Celeris System, point of care device for human cell therapyConcentration of PB-MNCs autologous cell therapy was produced by a filtration-based point-of-care device. All the procedures were performed in operatory room with anaesthesiologic support (propofol and/or peripheral block). Blood withdrawal (120 ml) was collected through a peripheral venous access. Blood was loaded, and gravity filtration was allowed to proceed until the upstream side of the filter had no remaining blood; filtration last about 10 minutes. During filtration, MNCs were captured in the filter while plasma, platelets (PLTs) and red blood cells (RBCs) were not retained. Immediately concentrate solution is injected in the perilesional area and intramuscular in the foot and the leg (0.2-0.3cc in boluses) below the knee, at intervals of 1-2 cm and to a mean depth of 1.5-2 cm, using a 21G needle. This procedure is repeated on each patient for three times, at intervals of 30-45 days from each other. | Device | A-PBMNC therapy |
Primary outcome
Amputation-free survival at 1 month
Time frame: 1 month
rate of non amputated limb 1 month after the intervention
Amputation-free survival at 3 months
Time frame: 3 months
rate of non amputated limb 3 months after the intervention
Amputation-free survival at 6 months
Time frame: 6 months
rate of non amputated limb 6 months after the intervention
Amputation-free survival at 12 months
Time frame: 12 months
rate of non amputated limb 12 months after the intervention
Amputation-free survival at 18 months
Time frame: 18 months
rate of non amputated limb 18 months after the intervention
Amputation-free survival at 24 months
Time frame: 24 months
rate of non amputated limb 24 months after the intervention
risk of death at 1 month
Time frame: 1 month
rate of dead subjects 1 month after the intervention
risk of death at 3 months
Time frame: 3 months
rate of dead subjects 3 months after the intervention
risk of death at 6 months
Time frame: 6 months
rate of dead subjects 6 months after the intervention
risk of death at 12 months
Time frame: 12 months
rate of dead subjects 12 months after the intervention
risk of death at 18 months
Time frame: 18 months
rate of dead subjects 18 months after the intervention
risk of death at 24 months
Time frame: 24 months
rate of dead subjects 24 months after the intervention
probability of healing at 1 month
Time frame: 1 month
rate of healed subjects 1 month after the intervention
probability of healing at 3 months
Time frame: 3 months
rate of healed subjects 3 months after the intervention
probability of healing at 6 months
Time frame: 6 months
rate of healed subjects 6 months after the intervention
probability of healing at 12 months
Time frame: 12 months
rate of healed subjects 12 months after the intervention
probability of healing at 18 months
Time frame: 18 months
rate of healed subjects 18 months after the intervention
probability of healing at 24 months
Time frame: 24 months
rate of healed subjects 24 months after the intervention
3 secondary outcomes
transcutaneous oxygen measurement (TcPO2) variation
Time frame: 0-3 months
Healing time
Time frame: within 24 months
rest pain
Time frame: 0-1-3 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Feb 2020.
- Background: PubMed 26391460Abu Dabrh AM, Steffen MW, Undavalli C, Asi N, Wang Z, Elamin MB, Conte MS, Murad MH. The natural history of untreated severe or critical limb ischemia. J Vasc Surg. 2015 Dec;62(6):1642-51.e3. doi: 10.1016/j.jvs.2015.07.065. Epub 2015 Sep 26.
- Background: PubMed 16908785Golomb BA, Dang TT, Criqui MH. Peripheral arterial disease: morbidity and mortality implications. Circulation. 2006 Aug 15;114(7):688-99. doi: 10.1161/CIRCULATIONAHA.105.593442. No abstract available.
- Background: PubMed 28096194Rigato M, Monami M, Fadini GP. Autologous Cell Therapy for Peripheral Arterial Disease: Systematic Review and Meta-Analysis of Randomized, Nonrandomized, and Noncontrolled Studies. Circ Res. 2017 Apr 14;120(8):1326-1340. doi: 10.1161/CIRCRESAHA.116.309045. Epub 2017 Jan 17.
- Background: PubMed 20404134Fantin A, Vieira JM, Gestri G, Denti L, Schwarz Q, Prykhozhij S, Peri F, Wilson SW, Ruhrberg C. Tissue macrophages act as cellular chaperones for vascular anastomosis downstream of VEGF-mediated endothelial tip cell induction. Blood. 2010 Aug 5;116(5):829-40. doi: 10.1182/blood-2009-12-257832. Epub 2010 Apr 19.
- Background: PubMed 23542777Baer C, Squadrito ML, Iruela-Arispe ML, De Palma M. Reciprocal interactions between endothelial cells and macrophages in angiogenic vascular niches. Exp Cell Res. 2013 Jul 1;319(11):1626-34. doi: 10.1016/j.yexcr.2013.03.026. Epub 2013 Mar 28.
- Background: PubMed 26982353Wynn TA, Vannella KM. Macrophages in Tissue Repair, Regeneration, and Fibrosis. Immunity. 2016 Mar 15;44(3):450-462. doi: 10.1016/j.immuni.2016.02.015.
- Background: PubMed 29765329Krzyszczyk P, Schloss R, Palmer A, Berthiaume F. The Role of Macrophages in Acute and Chronic Wound Healing and Interventions to Promote Pro-wound Healing Phenotypes. Front Physiol. 2018 May 1;9:419. doi: 10.3389/fphys.2018.00419. eCollection 2018.
- Background: PubMed 16410458Awad O, Dedkov EI, Jiao C, Bloomer S, Tomanek RJ, Schatteman GC. Differential healing activities of CD34+ and CD14+ endothelial cell progenitors. Arterioscler Thromb Vasc Biol. 2006 Apr;26(4):758-64. doi: 10.1161/01.ATV.0000203513.29227.6f. Epub 2006 Jan 12.
- Background: PubMed 24713821Jarajapu YP, Hazra S, Segal M, Li Calzi S, Jadhao C, Qian K, Mitter SK, Raizada MK, Boulton ME, Grant MB. Vasoreparative dysfunction of CD34+ cells in diabetic individuals involves hypoxic desensitization and impaired autocrine/paracrine mechanisms. PLoS One. 2014 Apr 8;9(4):e93965. doi: 10.1371/journal.pone.0093965. eCollection 2014.
- Background: PubMed 26038175Spaltro G, Straino S, Gambini E, Bassetti B, Persico L, Zoli S, Zanobini M, Capogrossi MC, Spirito R, Quarti C, Pompilio G. Characterization of the Pall Celeris system as a point-of-care device for therapeutic angiogenesis. Cytotherapy. 2015 Sep;17(9):1302-13. doi: 10.1016/j.jcyt.2015.04.006. Epub 2015 May 30.
- Background: PubMed 20031722Moriya J, Minamino T, Tateno K, Shimizu N, Kuwabara Y, Sato Y, Saito Y, Komuro I. Long-term outcome of therapeutic neovascularization using peripheral blood mononuclear cells for limb ischemia. Circ Cardiovasc Interv. 2009 Jun;2(3):245-54. doi: 10.1161/CIRCINTERVENTIONS.108.799361. Epub 2009 Mar 30.
- Background: PubMed 30053546Persiani F, Paolini A, Camilli D, Mascellari L, Platone A, Magenta A, Furgiuele S. Peripheral Blood Mononuclear Cells Therapy for Treatment of Lower Limb Ischemia in Diabetic Patients: A Single-Center Experience. Ann Vasc Surg. 2018 Nov;53:190-196. doi: 10.1016/j.avsg.2018.05.036. Epub 2018 Jul 25.
- Individual participant dataSharing planned: No. data should not be shared before study completion and approvation by all the collaborators. Sharing data before this time would jeopardize the integrity of the clinical trial process and risk the scientific validity of the results.
Related trials for Critical Limb Ischemia
RecruitingObservational study
miRNAs in Critical Limb Ischemia (miRNACLI)
Critical Limb Ischemia
Active, not recruitingObservational study
Laser Atherectomy and Sirolimus-eluting Balloon Angioplasty for CLTI
Chronic Limb Threatening Ischemia
Recruiting
Radiotracer-Based Perfusion Imaging of Patients With Peripheral Arterial Disease
Peripheral Artery Disease, Diabetes Mellitus
RecruitingObservational study
Vessel Recoil in Specific CLTI Populations
Chronic Limb Threatening Ischemia
Not yet recruiting
DCB Outcomes After Non-Compliant Balloon Vessel Preparation With or Without Scoring in Patients With Femoropopliteal Arterial Disease
Femoropopliteal Disease, Drug Coated Balloon
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.
Leonardo Ercolini, MD study chair
Vascular Surgery Unit San Donato Hospital Arezzo
Questions about this trial
What is this clinical trial studying?
A study testing Pall Celeris System, point of care device for human cell therapy in people with Critical Limb Ischemia and Diabetic Foot, run by Ospedale San Donato.
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 4 inclusion and 5 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: finished, as of the sponsor's last update on 5 Feb 2020. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Amputation-free survival at 1 month (time frame: 1 month). The study lists 18 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04255004, which also lists 42 linked publications.
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 5 Feb 2020.