A Multicenter Single-Arm Exploratory Study to Evaluate the Safety and Efficacy of Arterial Bypass to the Lower Extremity Using Biotubes Obtained with Subcutaneous Implantation of BTM1 for People with Critical Limb Ischemia.

JRCT ID: jRCT2072220062

Registered date:19/10/2022

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Patients with critical limb ischemia in the absence of optimal autologous veins.
• Date of first enrollment: 20/09/2022
• Target sample size: 12
• Study type: Interventional

Intervention(s)

1)Subcutaneous pockets are created by cutting the skin of the chest, abdomen, buttocks, or thighs and dissecting the subdermal layer.
The number and location of BTM1 implants per subject will be determined according to the following <1> to <3>.
<1> The minimum number of implants is 2, and the maximum number is 4.
<2> One implant in the abdomen is mandatory.
<3> The number of remaining implants (1 to 3) and their implantation sites (chest, abdomen, buttocks, or thighs) excluding <2> will be determined based on the body size and desire of the test subject and the medical judgment of the principal investigator or the subinvestigator (such as no skin abnormalities at the site, which can ensure adequate space for implantation).
2)Insert the sizer into the created subcutaneous pocket to ensure that there is enough space for implantation.
3)Remove BTM1 aseptically from the packaging bag and confirm that there are no deformations or abnormalities in appearance.
The size of BTM1 to be used will be selected at the discretion of the principal investigator or the subinvestigator depending on the body size of the test subject, etc.
4)BTM1 is inserted into the subcutaneous pocket and placed subcutaneously.
5)If subcutaneous hemorrhage occurs, complete hemostasis should be performed with an electrocautery knife, etc.
6)Insert and fix the blake drain subcutaneously.
7)Intradermal suture is performed, BTM1 is fixed subcutaneously, and the wound is closed.
8)Aspiration of air in BTM1 is initiated through the brake drain.
9)Two to seven days after implantation, echography and visual inspection of the implantation site confirm that the bleeding or exudate has subsided and remove the blake drain.
The site of implantation should also be checked by echography approximately 1 week after removal of the blake drain.
If echography shows blood or effusion around BTM1, it is removed by paracentesis.
10) BTM1 should remain in place for 4 to 24 weeks after implantation (as a rule, 8 weeks or more).
11) Again, the skin is cut and the subcutaneous tissue is dissected while hemostatic to remove BTM1.
12)After removing the connective tissue on the outer side of BTM1, the outer shell is removed and the formed biotube is taken out together with the middle core.
13) Remove the biotube from the core and wash with physiological saline.
14) A linearized rod is inserted into the biotube lumen and immersed in alcohol (70%) for 30 min in an immersion dish.
15) Wash the biotube again with physiological saline, and visually confirm that there is no noticeable deviation in the appearance, breakage, defect, or thickness.
16) As with autologous vein graft bypass, a syringe should be used to load saline inside the biotube to ensure that there is no leakage, and pressure monitors should be used to confirm pressure tolerance (presence or absence of turgor and bursting under 200 mmHg pressure overload conditions).
Also, use a tensile tester to measure the maximum strength to confirm that the standard strength (5 N) is satisfied.
Biotubes created by the above 1)-16) procedure are implanted into the subject's lower limb as an alternative vessel as well as an autologous vein graft.

Outcome(s)

• Primary Outcome: Ability of biotubes to form by the test instrument (BTM1).

Secondary Outcome

1) Procedural success with respect to implantation and extraction of the test device.
2) Technical success of bypass surgery involving peripheral anastomosis using biotubes formed by the test instrument.
3) Patency of the biotube at 12 weeks after implantation.
4) Improvement of symptoms (improvement of ischemic pain, improvement of wounds)
5) Avoidance of major amputation.
6) Rates of additional treatment during implantation of the test device and after biotube implantation
7) QOL during test device implantation and after biotube implantation.
8) Bypass graft diameter after bypass surgery.

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

(1)Patients for whom written informed consent has been obtained from the individual regarding their participation in the clinical trial.
(2)Patients aged 18 years or older at the time of informed consent
(3)Individuals with critical limb ischemia meeting ischemia (Ischemia)grade 2 or 3 (ABI <0.6, SPP <40 mmHg) in the Comprehensive Advanced Chronic Leg Ischemia (Chronic Limb Threatening Ischemia; CLTI) severity WIfI categorization (Ref. 15).
(4)Among patients for whom lower extremity arterial bypass is recommended, those who meet any of the following:
a.Global Vascular Guideline(GVG) GLASS(Global Anatomic Staging System) of (Ref. 8) the ischemic limb of stage III in the classification, which falls under WIfI classification clinical stage 2, 3 or 4
Ischemic limb of b.GLASS stage II that falls under WIfI class clinical stage 3 or 4
Ischemic limb of c.GLASS stage I or II that does not achieve adequate blood flow despite endovascular treatment (including clinical failure that does not lead to healing of the wound and does not improve clinical condition)
(5)Patients who meet the length and diameter (3 mm or higher) required for bypassing surgery and who do not have an optimal upper or lower extremity vein (for patients with chronic kidney disease stage G5, for patients with lower extremity vein) without abnormal findings such as varicocele, or who are judged to have no vein or difficult to harvest from a medical perspective based on the eligibility committee.
(6)Patients requiring peripheral anastomosis of bypass to the crural or pedal arteries below the knee
(7)Patients who are judged to be able to survive for at least 12 months and to be followed up for 12 weeks after bypass surgery at the time of informed consent.

Exclude criteria

(1)Patients with a general condition in which it is difficult to ensure the duration of implantation of the test device required for biotube formation because of conditions requiring immediate revascularization, etc.
(2)Patients with general condition judged to be difficult to accept operative procedures due to severe undernutrition (CONUT score 8-12) (Ref. 19) or severe complications, etc.
(3)Patients who may not have two or more implant sites for the test device because of poor skin condition or history of exposure to subcutaneous implants in the past.
(4)Patients undergoing invasive surgical procedures within 30 days before enrollment (excluding procedures for foot wounds)
(5)Patients with no target arteries on the peripheral side required for bypass surgery or a history of endovascular treatment at the site of planned peripheral anastomosis
(6)Occlusion of the artery proximal to the planned site of anastomosis on the central side of bypass surgery
Thromboendothelial removal during bypass surgery in the present study,
By releasing the occlusion by artificial vascular bypass Unavoidable patient.
(7)Patients in whom blood circulation distal to the planned site of distal anastomosis of bypass surgery cannot be confirmed (excluding patients in whom collateral circulation can be confirmed)
(8)Patients undergoing lower limb amputation proximal to the midfoot
(9)Patients with a history or concomitant malignancy (excluding those with no recurrence or no new onset for more than 5 years after treatment)
(10)Patients receiving immunosuppressive drugs for complications of autoimmune diseases or after transplantation
(11)Patients with a history of allergy to stainless steel or polyolefin resin
(12)Patients who are pregnant or may be pregnant
(13)Patients who are or are scheduled to participate in other clinical trials or interventional clinical studies
(14)Other than the above, patients who are judged to be inappropriate for the purpose of this clinical trial by the principal investigator or a sub-investigator due to medical conditions, etc. or safety reasons.

Related Information

• Primary Sponsor: Miyamoto Sinji
• Source(s) of Monetary Support: Japan Agency for Medical Research and Development