Cardiovascular Clinical Project to Evaluate the Regenerative Capacity of CardioCell in Patients With No-option Critical Limb Ischemia (N-O CLI)

Regeneration of Ischemic Damages in Cardiovascular System Using Wharton's Jelly as an Unlimited Source of Mesenchymal Stem Cells for Regenerative Medicine. Project of the National Centre for Research and Development (Poland) 'STRATEGMED II'. Cardiovascular Clinical Project to Evaluate the Regenerative Capacity of CardioCell in Patients With No-option Critical Limb Ischemia (N-O CLI)

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Critical Limb Ischemia
• Intervention / Treatment: Drug: Placebos; Drug: CardioCell

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.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Poland
  • Cracovia, Poland, 31-202
    • The John Paul II Hospital
  • Katowice, Poland, 40-635
    • Leszek Giec Upper-Silesian Medical Centre of the Silesian Medical University in Katowice

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Active Group; Patients randomized to the active treatment group will receive CardioCell consist 30 000 000 cells (suspended in 20 ml of 0.9% NaCl and 5% albumin); 15 000 000 via common femoral artery injection and 15 000 000 via intramuscular injections above the knee (ATK, 6 injection sites) and below the knee (BTK, 6 injection sites).	Drug: CardioCell; 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.; Other Names: CardioCell administration
Placebo Comparator: Control Group; Patients randomized to the placebo group will receive Placebos consist 0.9% NaCl and 5% albumin injections (in the same volumes as CardioCell) injections in the same manner.	Drug: Placebos; 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.; Other Names: Placebo administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in pain-free walking distance	Change in pain-free walking distance (6M FU vs index evaluation) between two groups (active vs placebo therapy).	6 month FU

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Amputation-free survival period	Amputation-free survival period evaluation of treated leg at 6 month and 1 year FU.	6 month and 1 year FU.
Ulcer-free survival	Ulcer-free survival (in patients without ulceration at baseline evaluation) of treated leg in period evaluation at 6 month and 1 year FU.	6 month and 1 year FU
Ulcer-extension free survival	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.	6 month and 1 year FU
Change in tissue oxygen/CO2 tension	Change in tissue oxygen/CO2 tension, assessed by NIRS method at each trial evaluation point.	45 days, 3 month, 6 month and 1 year FU
An improvement of tissue perfusion	An improvement of tissue perfusion assessed in MRI at each trial evaluation point.	45 days, 3 month, 6 month and 1 year FU
Change in transcutaneous pressure of O2	Change in transcutaneous pressure of O2 (tcpO2) between two groups (active vs placebo therapy) at each trial evaluation point.	45 days, 3 month, 6 month and 1 year FU
Change in ABI score	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.	45 days, 3 month, 6 month and 1 year FU
Quality of life improvement, assessed by SF-36 questionnaire	Quality of life improvement, assessed by SF-36 questionnaire or other dedicated for investigated population at each trial evaluation point.	45 days, 3 month, 6 month and 1 year FU

Collaborators and Investigators

• Sponsor: John Paul II Hospital, Krakow
• Collaborators: National Center for Research and Development, Poland; KCRI
• Investigators: Principal Investigator: Mariusz Trystuła, MD, John Paul II Hospital

Study record dates

Study Major Dates

• Study Start (Actual): April 19, 2018
• Primary Completion (Anticipated): May 31, 2021
• Study Completion (Anticipated): September 30, 2021

Study Registration Dates

• First Submitted: January 25, 2018
• First Submitted That Met QC Criteria: February 5, 2018
• First Posted (Actual): February 6, 2018

Study Record Updates

• Last Update Posted (Actual): April 9, 2021
• Last Update Submitted That Met QC Criteria: April 8, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Ischemia
• Other Study ID Numbers: CardioCell in N-O CLI

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No