Arterial Disease, Atherosclerosis, Peripheral Artery Disease
Conditions
Keywords
PAD, DCB, PTA, Sirolimus
Brief summary
This study aims to conduct a randomized, double blind, randomised controlled multicentre trial of sirolimus drug coated balloon versus standard percutaneous transluminal angioplasty for the treatment of superficial and popliteal arterial disease.
Detailed description
The burden of limb loss as a result of peripheral arterial disease (PAD) is high and this problem is set to worsen globally. Treatment of PAD primarily involves revascularisation of the limb. Angioplasty as a first line strategy of revascularization over surgical procedures has been adopted by most vascular centers. Local drug delivery using drug coated balloons (DCB) during angioplasty for PAD can successfully deliver effective local tissue concentrations of anti-proliferative drugs to the lesions in the artery involved in the PAD. This offers the potential for sustained anti-restenotic efficacy. Randomized trials have shown superiority of Paclitaxel DCBs over just plain-balloon angioplasty for treatment of PAD, and DCB is now considered the standard of care. However a recent meta-analyses which showed increased mortality at two years in patients treated with paclitaxel DCBs have called into question the safety of paclitaxel based DCBs. Alternative drugs for DCBs are therefore urgently needed and sirolimus offers an attractive alternative. Compared to Paclitaxel, sirolimus is cytostatic in its mode of action with a high margin of safety. It has a high transfer rate to the vessel wall and has been shown to effectively inhibit neointimal hyperplasia in the porcine coronary model. In the coronary artery interventions, preliminary clinical studies using Sirolimus DCBs have also shown excellent procedural and 6 month patency.
Interventions
DEVICEMagicTouch PTA sirolimus drug coated balloon (DCB)
For participants randomised to MagicTouch PTA sirolimus DCB, following successful plain balloon angioplasty of the arterial lesion, (defined as \<30% residual stenosis after treatment at rated burst pressure of the angioplasty balloon), MagicTouch PTA sirolimus coated balloon will be applied at the lesion after appropriate sizing using the diameter of the plain balloon angioplasty.
DEVICEPOBA standard balloon
For participants randomised to the standard balloon angioplasty group, a placebo standard balloon which is identical to the SCB will also be applied at the lesion after appropriate sizing using the diameter of the plain balloon angioplasty.
Sponsors
Concept Medical Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Eligible subjects will be randomised via a secure online system to a labelled device and to receive either Magic Touch sirolimus drug coated balloon in addition to standard balloon angioplasty or standard balloon angioplasty and placebo balloon.
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age ≥ 21 years or minimum age 2. Rutherford class 3 to 6 in the target limb Intraoperative Inclusion Criteria 3. Single or sequential de novo or re-stenotic lesions (stenosis of \> 50% or occlusions) from 2 to 20cm in the femoropopliteal arteries. Lesion is considered as one lesion if there is maximum of 30mm gap between lesions at discretion of investigator. Femoropopliteal arteries are superficial femoral artery, popliteal artery P1 and P2 4. Inflow free from flow limiting lesions (\<50% stenosis) confirmed by duplex or angiography. Subjects with flow limiting inflow lesions (\>50% stenosis) can be included if lesion had been treated successfully (\<30% residual stenosis) before or during the index procedure. 5. At least one non-occluded crural vessel (ie. without significant stenosis) with angiographically documented run off to the foot.
Exclusion criteria
1. Comorbid conditions limiting life expectancy ≤ 1 year 2. Subject is currently participating in another investigational drug or device study that has not reached first primary endpoint yet 3. Subject is pregnant or planning to become pregnant during the course of the study 4. Heel gangrene 5. Prior bypass surgery of target vessel 6. Planned amputation of the target limb 7. Previously implanted stent in the target lesion 8. Vulnerable or protected adults 9. Bleeding diathesis or another disorder such as gastrointestinal ulceration which restrict the use of clopidogrel or aspirin 10. Known allergy to sirolimus Intraoperative
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary patency at 6 months | 6 Months | Primary patency rate at 6 months defined as proportion of subjects with duplex ultrasonography-derived peak systolic velocity ratio of \< 2.4 (in absence of target lesion revascularisation) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| All-cause death | 1, 6, 12 and 24 Months | Proportion of subjects died by any cause |
| Major target limb amputation | 1, 6, 12 and 24 Months | Proportion of major target limb amputation |
| Target vessel thrombosis | From day 0 to day 14 | Proportion of subjects with target vessel thrombosis |
| Proportion of subjects who experienced either death at 6 month or major target limb amputation at 6 month or target vessel thrombosis within 14 days | Day 0 to day 14, 6 Months | Proportion of subjects who experienced either death at 6 month or major target limb amputation at 6 month or target vessel thrombosis within 14 days |
| Occurrence of adverse events (AEs), serious AEs and AEs related to device and Occurrence of adverse events (AEs), serious AEs and AEs related to device and procedure | From Day 0 to 24 Months Follow-up | Occurrence of adverse events (AEs), serious AEs and AEs related to device and Occurrence of adverse events (AEs), serious AEs and AEs related to device and procedure |
| Procedural Success | From Day 1 to discharge up to maximum of 30 days | Proportion of subjects with procedural success during hospital stay |
| Proportion of subjects who are free from clinically-driven Target Lesion Revascularization (TLR) | 6,12 and 24 Months | Proportion of subjects who are free from clinically-driven TLR |
| Proportion of subjects who are free from clinically-driven Target Vessel Revascularization (TVR) | 6,12 and 24 Months | Proportion of subjects who are free from clinically-driven Target Vessel Revascularization (TVR) |
| Primary patency | 12 and 24 Months | Primary patency rate at 12 and 24 months |
| Restenosis | 6, 12 and 24 Months | Proportion of subjects with restenosis |
| Subjects who are free from MAE | 6 Months | Proportion of subjects who are free from MAE |
| Amputation-free survival | 6, 12 and 24 Months | Amputation-free survival |
| Clinical Success | 6, 12 and 24 Months | Proportion of subjects with clinical Success at 6, 12 and 24 months, Clinical success is defined as Improvement in Rutherford classification compared to the pre-procedure Rutherford classification |
| Device success | Day 1 | Proportion of subjects with device success at day 1 |
| Technical success | Day 1 | Proportion of subjects with technical success at day 1 |
| Wound assessment (if any) | 1, 6, 12, 24 Months | Wound assessment (if any) |
| Toe Pressure or ABPI assessment | 6, 12, 24 Months | Toe Pressure or ABPI assessment |
| Device and procedure related death | 1, 6, 12 and 24 Months | Proportion of device and procedure related death |
Other
| Measure | Time frame | Description |
|---|---|---|
| Improvement of quality of life | 12 and 24 months | Mean change from baseline in EuroQol-5Dimensions (EQ-5D) health-related quality of life questionnaire score at 12 and 24 months. The score ranges from 0 to 1, and a higher score means a better outcome |
| Walking impairment | 12 and 24 months | Mean change from baseline in walking impairment questionnaire score at 12 and 24 months. The score ranges form 0% t 100%, and a higher score means a better outcome |
Countries
Singapore, Taiwan, Thailand
Contacts
Primary ContactEdward Choke
Outcome results
None listed