Critical Limb Ischemia
Conditions
Brief summary
The main objective of the CIRCULATE project is to compare the clinical outcomes of CardioCell administration in treatment of ischemic damages of cardiovascular system with control group, who will be treated by the administration of placebo during the sham procedure.
Detailed description
It is planned to enroll 105 patients into N-O CLI trial with randomization into active (CardioCell) therapy and sham procedure/placebo administration with 2:1 ratio. The primary research question of this project is to check if the administration of CardioCell could improve the clinical outcomes in patients with N-O CLI. There are several secondary questions, defined by secondary endpoints, e.g.: if the investigated treatment is possible to administered, if the investigated treatment is safe in each studied indication and way of CardioCell administration, if it is possible to define any selected subgroup in which the treatment results are significantly different than in whole group.
Interventions
DRUGCardioCell
Patients in the N-O CLI trial will receive a full dose of IMP three times during the trial: at baseline, after 45 days post index administration and after 3 months post index administration. IMP will be administered into femoral artery and intramuscularly with 50:50 proportion. The intramuscularly dose will be administered into muscles above and below the knee in 50:50 proportion.
DRUGPlacebos
Patients randomized to the control group will receive 0.9% NaCl and 5% albumin injections (in the same volume as CardioCell) in the same manner. Control group will receive the same amount of fluid used for WJMSCs preparation, without cells.
Sponsors
KCRI
National Center for Research and Development, Poland
John Paul II Hospital, Krakow
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
The Data and Safety Monitoring Board (DSMB) will be blinded at project start, but may request unblinding if necessary to accommodate effective review of data. Other than the DSMB (if necessary), the only other un-blinded parties, meaning that they will have knowledge as to the patient's treatment assignment, will be the PBTiK UJ CM employee who participates in randomization utilizing randomization lists and investigational medication preparation.
Intervention model description
The N-O CLI trial will enroll 105 patients with randomization into active and sham therapy with 2:1 ratio. Additional 5-10 subjects meeting inclusion/exclusion criteria will receive, in a non-blinded fashion, labelled CardioCell to determine the early uptake and retention of IMP in the target ischemic tissues.
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Patients able to walk * Male and female patients, aged 18-80 years * No-option CLI (definition: exhausted revascularization options including surgery or endovascular treatment) in Rutherford stage 4-5 * In case of bilateral N-O CLI, the limb with shorter claudication distance will be treated * Presence of adequate inflow (patent iliac and common femoral arteries) * Run-off through at least one (even partially seen) below-the-knee (BTK) artery * Signed informed consent
Exclusion criteria
* Malignancy * Moderate or severe immunodeficiency * Acute or chronic bacterial or viral infectious disease * Soft tissue disease or local infection in a place of required artery puncture * Pregnancy or breastfeeding * Any objective or subjective reason for inability to attend follow-up visits * Females of childbearing potential, who does not want to use a highly effective method of contraception * Females of childbearing potential who does not have a menstrual period confirmed and a negative highly sensitive urine or serum pregnancy test * Participation in any other clinical research study that has not reached the primary efficacy endpoint or otherwise would interfere with the patient's participation in this project * Life expectancy \< 1 year * Any concurrent disease or condition that, in the opinion of the investigator, would make the patient unsuitable for participation in the project
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in pain-free walking distance | 6 month FU | Change in pain-free walking distance (6M FU vs index evaluation) between two groups (active vs placebo therapy). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Ulcer-free survival | 6 month and 1 year FU | Ulcer-free survival (in patients without ulceration at baseline evaluation) of treated leg in period evaluation at 6 month and 1 year FU. |
| Ulcer-extension free survival | 6 month and 1 year FU | Ulcer-extension free survival (in patients with ulceration in the beginning of the trial) of treated leg in period evaluation at 6 month and 1 year FU. |
| Change in tissue oxygen/CO2 tension | 45 days, 3 month, 6 month and 1 year FU | Change in tissue oxygen/CO2 tension, assessed by NIRS method at each trial evaluation point. |
| Amputation-free survival period | 6 month and 1 year FU. | Amputation-free survival period evaluation of treated leg at 6 month and 1 year FU. |
| Change in transcutaneous pressure of O2 | 45 days, 3 month, 6 month and 1 year FU | Change in transcutaneous pressure of O2 (tcpO2) between two groups (active vs placebo therapy) at each trial evaluation point. |
| Change in ABI score | 45 days, 3 month, 6 month and 1 year FU | Change in ABI score at each trial evaluation point. The ankle-brachial index (ABI) is the ratio of the blood pressure at the ankle to the blood pressure in the upper arm and is calculated by dividing the systolic blood pressure at the ankle by the systolic blood pressure in the arm. An ABI between and including 0.9 and 1.2 is considered normal, while a lesser than 0.9 indicates peripheral arterial disease. An ABI value of 1.3 or greater is also considered abnormal, and suggests calcification of the walls of the arteries and incompressible vessels. ABI score progression towards the normal range is considered as a better outcome. |
| Quality of life improvement, assessed by SF-36 questionnaire | 45 days, 3 month, 6 month and 1 year FU | Quality of life improvement, assessed by SF-36 questionnaire or other dedicated for investigated population at each trial evaluation point. |
| An improvement of tissue perfusion | 45 days, 3 month, 6 month and 1 year FU | An improvement of tissue perfusion assessed in MRI at each trial evaluation point. |
Countries
Poland
Outcome results
None listed