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

Primary Purpose

Critical Limb Ischemia

Status

Unknown status

Phase

Phase 2

Locations

Poland

Study Type

Interventional

Intervention

CardioCell

Placebos

About this trial

This is an interventional treatment trial for Critical Limb Ischemia

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

The John Paul II Hospital
Leszek Giec Upper-Silesian Medical Centre of the Silesian Medical University in Katowice

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Active Group

Control Group

Arm Description

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).

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.

Outcomes

Primary Outcome Measures

Change in pain-free walking distance

Change in pain-free walking distance (6M FU vs index evaluation) between two groups (active vs placebo therapy).

Secondary Outcome Measures

Amputation-free survival period

Amputation-free survival period evaluation of treated leg at 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.

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.

Change in tissue oxygen/CO2 tension

Change in tissue oxygen/CO2 tension, assessed by NIRS method at each trial evaluation point.

An improvement of tissue perfusion

An improvement of tissue perfusion assessed in MRI at each trial evaluation point.

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.

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.

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.

Full Information

NCT ID

NCT03423732

First Posted

January 25, 2018

Last Updated

April 8, 2021

Sponsor

John Paul II Hospital, Krakow

Collaborators

KCRI, National Center for Research and Development, Poland

1. Study Identification

Unique Protocol Identification Number

NCT03423732

Brief Title

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

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)

Study Type

Interventional

2. Study Status

Record Verification Date

April 2021

Overall Recruitment Status

Unknown status

Study Start Date

April 19, 2018 (Actual)

Primary Completion Date

May 31, 2021 (Anticipated)

Study Completion Date

September 30, 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

John Paul II Hospital, Krakow

Collaborators

KCRI, National Center for Research and Development, Poland

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Critical Limb Ischemia

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2, Phase 3

Interventional Study Model

Parallel Assignment

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.

Masking

ParticipantCare ProviderInvestigatorOutcomes 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.

Allocation

Randomized

Enrollment

50 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Active Group

Arm Type

Active Comparator

Arm Description

Arm Title

Control Group

Arm Type

Placebo Comparator

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

CardioCell

Other Intervention Name(s)

CardioCell administration

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Placebos

Other Intervention Name(s)

Placebo administration

Intervention Description

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.

Primary Outcome Measure Information:

Title

Change in pain-free walking distance

Description

Change in pain-free walking distance (6M FU vs index evaluation) between two groups (active vs placebo therapy).

Time Frame

6 month FU

Secondary Outcome Measure Information:

Title

Amputation-free survival period

Description

Amputation-free survival period evaluation of treated leg at 6 month and 1 year FU.

Time Frame

6 month and 1 year FU.

Title

Ulcer-free survival

Description

Ulcer-free survival (in patients without ulceration at baseline evaluation) of treated leg in period evaluation at 6 month and 1 year FU.

Time Frame

6 month and 1 year FU

Title

Ulcer-extension free survival

Description

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.

Time Frame

6 month and 1 year FU

Title

Change in tissue oxygen/CO2 tension

Description

Change in tissue oxygen/CO2 tension, assessed by NIRS method at each trial evaluation point.

Time Frame