To assess the safety and efficacy of the paclitaxel drug-eluting balloon IN.PACT 014 versus conventional, optimal percutaneous transluminal angioplasty (PTA) for the treatment of patients with chronic total occlusions in the infrapopliteal arteries…
ID
Source
Brief title
Condition
- Arteriosclerosis, stenosis, vascular insufficiency and necrosis
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To assess the efficacy of the IN.PACT 014 by comparing the Late Lumen Loss
(LLL) 9 months after the index procedure of the investigational product vs
optimal (conventional) PTA
Secondary outcome
• Composite Safety Endpoint: A composite of freedom from device- and
procedure-related mortality within 30 days, freedom from major target limb
amputation and freedom from clinically-driven TLR within 9 months post-index
procedure.
• Major Adverse Event (MAE) rate, defined as a composite of all-cause
mortality, target limb major amputation and clinically-driven TLR through 3, 6,
9, 12, 24 and 36 months.
• Functional flow assessment at 3, 6, 9, 12 and 24 month, defined as absence
of target lesion occlusion (no flow) assessed by duplex ultrasound.
• Death of any cause and cardiovascular related deaths through 3, 6, 9, 12 and
24 months.
• Rate of major target limb amputation through 30 days, 3, 6, 9 ,12 and 24
months.
• Rate of CD-TLR through 3, 6, 9, 12 and 24 months.
• Rate of Mechanically Driven TLR through 30 days.
• Rate of TLR through 3, 6, 9, 12 and 24 months.
• Rate of CD-TVR through 3, 6, 9, 12 and 24 months.
• Rate of TVR through 3, 6, 9, 12 and 24 months.
• Status of wound healing (completely healed - improvement - unchanged -
worsened) at 30 days, 3, 6, 9, 12 and 24 months.
• Rate of thrombosis at the target lesion through 30 days, 3, 6, 9, 12 and 24
months.
• Device success (for investigational device only)
Device success is defined as successful drug delivery, balloon inflation,
deflation and retrieval of the intact study device without burst below the
rated burst pressure (RBP).
• Clinical success
Clinical success is defined as residual stenosis of <= 30% without procedural
complications (death, major target limb amputation, thrombosis of the target
lesion, or TVR) prior to discharge.
Background summary
Peripheral arterial disease (PAD) is a commonly occurring medical condition
that involves atherosclerosis in vessels located outside the heart and brain.
PAD affects an estimated 27 million adults in Europe and North America.Patients
suffering from PAD generally experience a significant reduction in
health-related quality of life (QOL).
Patients with PAD tend to experience an increase in morbidity and a reduction
in health status measures of health-related QOL. Potential consequences of
lower extremity arterial disease include reduced mobility, limb pain, gangrene,
and amputation, as well as increased mortality, amongst others. Critical limb
ischemia (CLI) refers to severe persistent rest pain requiring treatment with
analgesics, ulceration or gangrene on the distal extremity. PAD located
below-the-knee is more likely to be diffuse and progressive than above-the-knee
PAD, which is often characterized by multilevel disease and heavily calcified
lesions. Patients often present with symptoms of CLI as opposed to
claudication. Comorbidities such as diabetes and renal failure occur rather
frequently alongside PAD.
Outcomes of percutaneous angioplasty interventions and/or stenting for
below-the-knee PAD are available throughout the literature. Findings suggest
that use of stents that elute anti-proliferative agents may result in further
benefit in terms of restenosis rates as compared to uncoated PTA and bare metal
stents.
Paclitaxel is an antineoplastic drug that has demonstrated sustained inhibition
of smooth muscle cell proliferation in several pre-clinical studies.
Publications assessing effectiveness of local administration of paclitaxel on
restenosis via drug-coated balloons in the femoropopliteal artery have shown
promising results, as seen by reduced neointimal proliferation in the
peripheral arteries. Recent publications have discussed outcomes regarding use
of paclitaxel-coated balloons in patients with below-the-knee disease. Early
studies using paclitaxel-coated balloons to manage complex below-the-knee
lesions have shown paclitaxel-coated balloons to be superior to uncoated
balloons with regard to restenosis rates. More recently, the results of a
retrospective analysis of the Lutonix Paclitaxel coated balloon were published.
Authors conclude that the Lutonix DCB showed safety and efficacy in BTK
interventions in CLI patients.
Study objective
To assess the safety and efficacy of the paclitaxel drug-eluting balloon
IN.PACT 014 versus conventional, optimal percutaneous transluminal angioplasty
(PTA) for the treatment of patients with chronic total occlusions in the
infrapopliteal arteries. This information can be used for regulatory purposes.
Study design
This is a prospective, multi-center, randomized (1:1) study to evaluate the
efficacy and safety of the IN.PACT 014 in the treatment of CTOs in the
infrapopliteal arteries.
All subjects will be followed with baseline, procedure, discharge, and
follow-up evaluations at 30 days, 3, 6, 9, 12 and 24 months post procedure.
Intervention
The IN.PACT 014 is a medical device that contains an ancillary medicinal
substance. The product consists of an over-the-wire (OTW) balloon catheter with
a drug-coated balloon at the distal tip. The product is indicated for
percutaneous transluminal angioplasty in patients with obstructive disease of
peripheral arteries. The IN.PACT 014, including its components, is considered
an investigational product.
The medicinal substance component, referred to as the Freepac* drug coating,
consists of the medicinal substance paclitaxel and the excipient urea provides
a nominal drug dose density of 3.5µg/mm2. The device component physically
dilates the vessel lumen by Percutaneous Transluminal Angioplasty (PTA)
(primary mode of action), and the medicinal substance provides a
pharmacological agent targeted towards reducing the injury response that leads
to restenosis (secondary mode of action).
Study burden and risks
Based on our current knowledge, participation into the IN.PACT BTK Clinical
Study does not impose significant additional risks to the subject comparing to
existing treatment option (ie. PTA, stenting). There is a high probability that
subjects benefit when using a DCB as studies have shown clinical and
angiographic superiority when compared to standard PTA in related treatment
areas.
It is anticipated that the potential benefits of the study outweigh the
potential risks; therefore the investigation is considered justified. It is
possible in any clinical trial that unanticipated effects can happen which are
not yet known at this time.
Endepolsdomein 5
Maastricht 6229 GW
NL
Endepolsdomein 5
Maastricht 6229 GW
NL
Listed location countries
Age
Inclusion criteria
1. Age >=18 years
2. Subject has been informed of the nature of the study, agrees to participate and has signed an Ethics Committee (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. Subject has documented chronic Critical Limb Ischemia (CLI) in the target limb prior to the study procedure with Rutherford Clinical Category 4 or 5.
5. Subjects with documented infection grade 0-2 and ischemia grade 2-3 according to the WIfI classification.
6. Life expectancy >1 year in the Investigator*s opinion.
7. Reference Vessel Diameter (RVD) 2 - 4 mm, and confirmed by DUS assessment.
8. Total occlusions (100% stenosis) with total lesion length >=40mm (by visual estimate).
9. The lesion must be located in the infrapopliteal arteries and above the ankle joint. Lesions may not extend above the tibioperoneal trunk (P3 segment of the popliteal artery) or below the ankle joint (arteries of the foot), nor can the treatment (investigational device or standard PTA, including pre-dilatation) extend beyond these indicated regions for more than 1 cm.
Note:
• A target lesion can extend into the P3 segment in case it involves a straight lesion extending from the target vessel.
• Non-significant stenosis below the ankle joint can be allowed in case this is not part of the target lesion and does not require treatment
10. Multiple lesions can be treated if they are located in separate vessels but all lesions must meet the protocol specified criteria.
11. Presence of documented run-off to the foot (clearly visible dorsalis pedis, pedal arch or plantar arteries by angiography). Target vessel should give direct or indirect run-off to the foot
12. Inflow free from flow-limiting lesion confirmed by angiography. Patients with flow-limiting inflow lesions (>= 50% stenosis) can be included if lesion(s) have been treated successfully before enrollment, with a maximum residual stenosis of <=30% per visual assessment. If an inflow lesion must be treated within the P3 segment of the popliteal artery, there must be a minimum of 3 cm healthy tissue 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 <=30% Residual diameter stenosis of the target lesion and by functional assessment of the distal flow by intra-operative Doppler: recording of biphasic or triphasic wave signal with rapid take-off distal to the target lesion.
Exclusion criteria
1. Subject unwilling or unlikely to comply to the appropriate follow-up times for the duration of the study.
Note: the investigator should discuss the follow-up requirements extensively during the informed consent process to ensure that the subject is fully aware about the expectations and is willing to comply with the follow-up schedule.
2. Planned index limb amputation above the metatarsal level, or any other planned major surgery within 30 days pre or post-procedure. A planned amputation including and below the metatarsal level (1 or multiple rays) is accepted.
3. Lesion and / or occlusions located or extending in the popliteal artery or below the ankle joint space.
Note:
• A target lesion can extend into the P3 segment in case it involves a straight lesion extending from the target vessel
• Non-significant stenosis below the ankle joint can be allowed in case this is not part of the target lesion and does not require treatment.
4. Significant (>=50% DS) inflow lesion or occlusion in the ipsilateral Iliac, SFA and popliteal arteries left untreated.
5. Failure to obtain a <=30% residual stenosis in pre-existing, hemodynamically significant (>=50% DS) inflow lesions in the ipsilateral iliac, SFA and popliteal artery. Inflow lesions should be treated per standard of care.
6. Prior stent(s) or bypass surgery within the target vessel(s) (including stents placed within target vessels during the index procedure prior to randomization).
7. Previous DCB procedure in the target vessel within 6 months prior to index procedure.
8. Aneurysm in the target vessel.
9. Angiographic evidence of thrombus within target limb.
10. Pre-dilation resulted in a major (>= Grade D) flow-limiting dissection (observed on 2 orthogonal views) or residual stenosis >30%.
11. Use of alternative therapy, e.g. atherectomy, cutting balloon, laser, radiation therapy, stents as part of target vessel treatment. Note: Use of stents is only allowed for bailout stenting.
12. Recent MI or stroke <30 days prior to the index procedure.
13. Heart failure with Ejection Fraction <30%.
14. Known or suspected active infection at the time of the index procedure (abnormal white blood cell count, fever, sepsis or positive blood culture), excluding an infection of a lower extremity wound on the target limb (only WIfI infection grade 0-2 allowed).
15. Subjects with infection grade 3 and ischemia grade 0 and 1 according to WIfI classification.
16.Subjects with neurotrophic ulcers, heel pressure ulcers or calcaneal ulcers with a risk for major amputation.
17. Subjects with documented active osteomyelitis, excluding the phalanges, that is beyond cortical involvement of the bone per clinical judgement.
18. Impaired renal function (GFR <20 mL/min) or patients on dialysis.
19. Subject with vasculitis, systemic Lupus Erythematosus or Polymyalgia Rheumatica on active treatment.
20. Patient receiving systemic corticosteroid therapy (expected dosage exceeding 5mg of prednisolone or equivalent, per day during the initial 9 months after procedure).
21. This criteria has been removed
22. Known allergies or sensitivities to heparin, aspirin (ASA), other anticoagulant/anti-platelet therapies which could not be substituted, and/or paclitaxel or an allergy to contrast media that cannot be adequately pre-treated prior to the index procedure.
23. The patient is currently enrolled in another investigational device or drug trial that is interfering with the endpoints of this study.
24. Female subjects who are breast-feeding at the time of enrollment
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| ClinicalTrials.gov | NCT02963649 |
| CCMO | NL62158.091.17 |