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

Critical Limb Ischemia Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03423732
• Other study ID #: CardioCell in N-O CLI
• Status: Active, not recruiting
• Phase: Phase 2/Phase 3
• Start date: April 19, 2018
• Est. completion date: September 30, 2021

Study information

• Verified date: April 2021
• Source: John Paul II Hospital, Krakow
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 50
• Est. completion date: September 30, 2021
• Est. primary completion date: May 31, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Critical Limb Ischemia
• Ischemia

Intervention

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.
• 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.

Locations

Country	Name	City	State
Poland	The John Paul II Hospital	Cracovia
Poland	Leszek Giec Upper-Silesian Medical Centre of the Silesian Medical University in Katowice	Katowice

Sponsors (3)

Lead Sponsor	Collaborator
John Paul II Hospital, Krakow	KCRI, National Center for Research and Development, Poland

Country where clinical trial is conducted

Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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