AcoArt Litos PCB Below-the-knee Global Trial

Chronic Limb-Threatening Ischemia Clinical Trial

Official title:

Prospective Multi-Center Randomized Controlled Trial to Evaluate the Safety and Efficacy of AcoArt Litos Paclitaxel Coated Percutaneous Transluminal Angioplasty (PTA) Balloon Versus Non-Coated Standard Balloon Angioplasty for the Treatment of Infrapopliteal Obstructions in Patients With Chronic Limb-Threatening Ischemia

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06330493
• Other study ID #: AcoArt BTK Global Trial
• Status: Not yet recruiting
• Phase: N/A
• Start date: June 2024
• Est. completion date: December 2030

Study information

• Verified date: May 2024
• Source: Acotec Scientific Co., Ltd
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The objective of this study is to assess whether efficacy of the AcoArt Litos PCB is superior and whether safety of AcoArt Litos PCB is noninferior to the control device (FDA cleared PTA Balloon Catheter) regarding treatment of obstructions in the infrapopliteal arteries (located distal to the P3 segment of the popliteal artery and extending to the tibiotalar joint) in patients presenting with chronic limb-threatening ischemia (CLTI)(Rutherford 4-5)

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 288
• Est. completion date: December 2030
• Est. primary completion date: October 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• General Inclusion Criteria

1. Age = 18 years at the time of consent;

2. Subjects has been informed of the nature of the study, is willing to comply with all required follow-up evaluations within the defined follow-up visit windows and has signed an Institutional Review Board(IRB)/Ethics Commitee(EC) approved consent form;

3. Female subjects of childbearing potential have a negative pregnancy test = 7 days before the procedure and are willing to use a reliable method of birth control for the duration of study participation. Female subjects will be exempted from this requirement in case they are sterile, infertile, or have been post-menopausal for at least 12 months (no menses);

4. Life expectancy > 1 year in the Investigator's opinion;

5. Subject presenting with documented chronic limb-threatening ischemia(CLTI) in the target limb defined as Rutherford category 4 or 5;

6. In case of Rutherford category 5: Subjects with documented wound score 0-1, infection grade 0-2 and ischemia grade 2-3 according to the wound ischemia foot infection (WIfI) classification;

7. No other prior surgical or vascular interventions within 2 weeks before and/or planned 30 days after the protocol treatment.

• Angiographic Inclusion Criteria

8. Reference Vessel Diameter(RVD) =2.0 and = 4.0mm and able to be treated with available device size matrix;

9. Total occlusion within the target veseel and cumulative lesion length = 140mm;

10. The lesion must be located in the infrapopliteal arteries and above the ankle joint. Lesions may not extend proximal to the P3 segment of the popliteal artery indicated by the tibial plateau or below the tibiotalar joint(arteries of the foot). The treatment(investigational device or PTA, including pre-dilatation) may not extend beyond these indicated regions for more than 1cm;

11. Presence of documented run-off to the foot(clearly visible at least one of the following run-off vessels; dorsalis pedis or pedal arch or plantar arteries by angiography). The target vessels should give direct or indirect run-off to the foot;

12. Absence of flow-limiting(= 50% stenosis) in-flow lesions confirmed by angiography. Patients with flow-limiting inflow lesions can be included if the lesion(s) have been treated successfully before enrollment, with a maximum residual restenosis of =30% per visual assessment. If an inflow lesion must be treated within or proximal to the P3 segment of the popliteal artery, there must be a minimum of 3 cm healthy vascular segment between this(treated) lesion and the infrapopliteal target lesion;

13. Successful pre-dilatation of the(entire) target lesion. Success being documented by angiographic visual estimate of = 50% residual diameter stenosis of the target lesion and no flow limiting dissection(< Grade D dissection). Target lesion is not considered non-dilatable by the operator due to concentric, circumferential calcium and target lesion can be treated successfully by balloon angioplasty without the need for bail-out stenting.

Exclusion Criteria:

• General Exclusion Criteria

1. Planned index limb amputation above the metatarsal level, or any other planned major surgery within 30 days pre- or post-procedure. A planed amputation including and below the metatarsal level(1 or multiple rays) is accepted.

2. Recent MI or stroke < 30 days prior to the index procedure;

3. Known or suspected active infection at the time of the index procedure(abnormal white blood cell count, fever, sepsis, or positive blood culture), with the exception of a localized, controlled infection of a lower extremity wound on the target limb(only WIfI infection grade 0-2 allowed);

4. Subjects with infection grade 3 and ischemia grade 0 and 1 according to WIfI classification;

5. Subjects not independently ambulating.

6. Subjects with neurotrophic ulcers, heel pressure ulcers or calcaneal ulcers with a risk for major amputation; Subjects with uncomplicated ulcers can be included;

7. Subjects with documented active osteomyelitis, excluding the phalanges, that is beyond cortical involvement of the bone per clinical judgement;

8. Subjects with vasculitis, systemic Lupus Erythematosus or polymyalgia rheumatica on active treatment;

9. Subjects with impaired renal function defined as eGFR <30 ml/min or on dialysis;

10. Patient receiving systemic corticosyeroid therapy(expected dosage exceeding 5 mg of prednisolone or equivalent, per day, during the initial 9 months after procedure);

11. Known allergies or sensitivities to heparin, aspirin(ASA), other anticoagulant/anti-platelet therapies which could not be substitued, and/or paclitaxel or an allergy to contrast media that cannot be adequately pre-treated prior to the index procedure;

12. Subjects currently enrolled in another investigational device, drug, or biological trial;

13. Femal subjects who are breast feeding at the time of enrollment;

14. Significant gastrointestinal bleeding or any coagulopathy that would contraindicate the use of anti-platelet therapy;

15. Any severe medical comorbidities(e.g., untreated CAD/CHF, NYHA class IV heart failure, Left Ventricular ejection fraction(LVEF) </= 30%(obtained within 1 month of index procedure), severe COPD, metastatic malignacy, etc.) that would preclude compliance with the study protocol or currently receiving immune-suppressive, chemotherapeutic, or radiation therapy;

• Angiographic Exclusion Criteria

16. Occlusions located or extending into the popliteal artery or distal to the ankle joint space;

17. Untreated (=50% measured by angiography) inflow lesion or occlusion in the ipsilateral iliac, SFA nad popliteal arteries;

18. Failure to obtain a =30% residual stenosis in pre-existing, hemodynamically significant(=50% measured by angiography) in flow lesions in the ipsilateral iliac, SFA and popliteal artery. Inflow lesions should be treated per standard of care;

19. Prior stent(s) or bypass surgery within the target vessel(s) (including stents placed within target vessels during the index procedure prior to randomization);

20. Previous procedure with drug-coated balloons in the target vessels within 6 months prior to index procedure.

21. Aneurysm in the target vessel;

22. Angiographic evidence of thrombus within target limb;

23. Pre-dilatation resulted in a major(= Grade D) flow-limiting dissection(observed on 2 orthogonal views) or residual stenosis >50%;

24. Use of alternative therapy, e.g. atherectomy, scoring balloon, laser, radiation therapy, stents as part of target vessel treatment.

Related Conditions & MeSH terms

• Chronic Limb-Threatening Ischemia
• Ischemia

Intervention

Device:
• PCB
Paclitaxel coated PTA balloon catheter
• PTA
Non-coated FDA cleared standard percutaneous transluminal angioplasty balloon catheter

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Acotec Scientific Co., Ltd

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Primary Efficacy Endpoint: Composite of freedom from major amputation and primary patency	Composite of freedom from major amputation (above ankle amputation) and primary patency at 6 months. Primary patency is defined as absence of target lesion occlusion (no flow) as determined by duplex ultrasound and/or clinically driven target lesion revascularization (CD-TLR). CD-TLR is defined as revascularization due to restenosis of = 70% in the target lesion and; Wound persistence and/or; Increase in size of pre-existing wounds and/or; Occurrence of new wounds and/or; Deterioration of Rutherford Class; Hemodynamic change: decrease in TBI of 0.15 or more.	6 months
Primary	Primary Safety Endpoint: Composite of MALE and POD (Major Adverse Limb Event + Peri-Operative Death)	Major adverse limb event (MALE, defined as the composite of above-ankle amputation or major reintervention (new bypass graft, jump/interposition graft revision, or thrombectomy/thrombolysis) of the index limb involving a below-the-knee artery) and perioperative death (POD) at 30 days.	30 days
Secondary	Composite of Limb Salvage and Primary Patency	Composite of Limb Salvage and Primary Patency includes freedom from: above ankle amputation in index limb, 100% total occlusion of target vessel, binary restenosis of target lesion and clinically-driven target lesion revascularization (CD-TLR);	1, 3, 12, 24, 36 months
Secondary	Patency rate	Patency rate is defined as the absence of target lesion occlusion(flow/no flow) as determined by duplex ultrasound and/or angiography and freedom from clinically-driven TLR;	1, 3, 6, 12, 24, 36 months
Secondary	Freedom from CD-TLR	CD-TLR is defined as revascularization due to restenosis of = 70 % in the target lesion and; Wound persistence and/or; Increase in size of pre-existing wounds and/or; Occurrence of new wounds and/or; Deterioration of Rutherford Class; Hemodynamic change: decrease in TBI of 0.15 or more.	1, 3, 6, 12, 24, 36 months
Secondary	Re-occlusion rate of target lesion	Re-occlusion rate of target lesion as determined by duplex ultrasound(no flow) and/or angiography;	1, 3, 6, 12, 24, 36 months
Secondary	Rate of Major adverse events(MAE)	MAE is defined as all-cause death, target limb major amputation and CD-TLR;	1, 3, 6, 12, 24, 36 months
Secondary	Rate of target limb major amputation	Rate of target lmb major amputations at 1, 3, 6, 12, 24, 36, 48 and 60 months;	1, 3, 6, 12, 24, 36, 48, 60 months
Secondary	Rate of all-cause death	Rate of all-cause death at 1, 3, 6, 12, 24, 36, 48 and 60 months;	1, 3, 6, 12, 24, 36, 48, 60 months
Secondary	Amputation free survival rate	Amputation free survival rate at 1, 3, 6, 12, 24, 36, 48 and 60 months;	1, 3, 6, 12, 24, 36, 48, 60 months
Secondary	Change in ankle-brachial index(ABI)	Change in ABI from pre-procedure to 1, 3, 6, 12, 24 and 36 months	1, 3, 6, 12, 24, 36 months
Secondary	Change in toe-brachial index(TBI)	Change in TBI from pre-procedure to 1, 3, 6, 12 and 24 months	1, 3, 6, 12, 24 months
Secondary	Change in Rutherford category	Change in Rutherford category from pre-procedure to 1, 3, 6, 12, 24 and 36 months	1, 3, 6, 12, 24 and 36 months
Secondary	Change in EQ-5D	Change in EQ-5D from pre-procedure to 1,3, 6,12, 24 and 36 months	1, 3, 6, 12, 24 and 36 months
Secondary	Change in VascuQol	Change in VascuQol from pre-procedure to 1,3, 6,12, 24 and 36 months	1, 3, 6, 12, 24 and 36 months
Secondary	Primary sustained clinical improvement	An improvement shift in the Rutherford classification of 1 class in amputation-free, clinically driven TLR-free surviving patients at 1 year	1 year
Secondary	Secondary sustained clinical improvement	An improvement shift in the Rutherford classification of 1 class including the need for clinically driven TLR in amputation-free surviving patients at 1 year	1 year
Secondary	Wound healing	The wound will be evaluated at 1, 3, 6, 12, 24 and 36months	1, 3, 6, 12, 24 and 36 months
Secondary	Rate of Device Success	Device Success is defined as exact deployment of the device according to the instructions for use, as documented with suitable imaging modalities, and in the case of digital subtraction angiography in at least 2 different imaging projections	During the procedure(After using the PCB catheter)
Secondary	Rate of Technical Success	Technical Success is defined as successful vascular access and completion of the endovascular procedure and immediate morphological success with = 50% residual diameter stenosis in the treated lesion on completion angiography	During the procedure(After using the PCB catheter)
Secondary	Rate of Procedure Success	Evidence of both acute technical success and absence of safety events(e.g., death, stroke, myocardial infraction, acute onset of limb ischemia, index bypass graft or treated segment thrombosis, and/or need for urgent/emergent vascular surgery) within 72 hours of the index procedure	within 72 hours of the index procedure