Peripheral Arterial Disease
Conditions
Brief summary
The T.I.N.T.I.N. study investigates the safety and efficacy of the combination therapy with the Luminor drug coated balloon (DCB) and the iVolution stent in the treatment of TASC C and D femoropopliteal lesions. An expected total of 100 patients will be treated in the scope of this study. The lesion is located within the native superficial femoral artery and/or the popliteal artery. Prior to dilatation with the Luminor DCB, pre-dilatation with the Oceanus balloon is mandatory. After dilatation with the Luminor DCB, stenting with the iVolution stent need to be performed. Post-dilatation can be performed according to the physician's discretion. Patients will be invited for a follow-up visit at 1, 6, 12, 24, 36, 48 and 60 month post-procedure. The primary efficacy endpoint of the study is defined as the freedom from clinically-driven target lesion revascularization (TLR) at 12 months. Secondary endpoints include primary patency rate at 6 and 12 months, freedom from clinically-driven TLR at 6, 24, 36, 48 and 60 months, clinical success at 1, 6, 12, 24, 36, 48 and 60 months and freedom from serious adverse events at pre-discharge, 1, 6, 12, 24, 36, 48 and 60 months follow-up.
Detailed description
The objective of this clinical investigation is to evaluate, in a controlled setting, the long-term safety and efficacy of the combination therapy with the Luminor DCB and the iVolution stent post CE-certification and according to the indications of the Instructions for use (IFU) with focus on the treatment of TASC C and D femoropopliteal atherosclerotic lesions. Patients will be selected based on the investigator's assessment, evaluation of the underlying disease and the eligibility criteria. The patient's medical condition should be stable, with no underlying medical condition which would prevent them from performing the required testing or from completing the study. Patients should also be geographically stable, willing and able to cooperate in this clinical study and remain available for long-term follow-up. A patient is considered enrolled in the study after obtaining the patients informed consent, if there is full compliance with the study eligibility criteria and after successful guidewire passage through the study target lesion. Prior to the index procedure the following tests and clinical data will be collected: informed consent for data collection, demographics, medical history, medication record, physical examination, clinical category of chronic limb ischemia (Rutherford category) and resting ankle-brachial index (ABI). During the procedure, the vascular access can be achieved to the investigator's standard clinical practice. After successful lesion passage, diagnostic angiography of the lesion area and distal run-off is performed and angiographic measurements (vessel diameter, percentage stenosis and lesion length) are collected. All inflow-limiting lesion will be treated according to the investigators standard clinical practice before treatment of the target lesion. Pre-dilatation of the target lesion is mandatory with the Oceanus balloon. After pre-dilatation, a least one Luminor DCB will be inflated and at least 1 iVolution stent will be deployed at the target lesion. At the physician's discretion, post-dilatation can be performed. No other adjunctive therapies (atherectomy, laser) are allowed. The complete femoropopliteal vasculature should be treated in one single session, staged interventions are not allowed. All outflow-limiting lesions must be treated according to the hospital treatment standard. The regular follow-ups are necessary to monitor the condition of the patient and the procedure. Patients will be invited for a follow-up visit at 1, 6, 12, 24, 36, 48 and 60 months after the index procedure. The 24, 36, 48 and 60 month follow-up can be conducted via a phone call. The following data will be collected during these follow-up visit: medication record, physical examination, rutherford categorization, ABI and color flow doppler ultrasound.
Interventions
DEVICECombination therapy DCB + stent
Patients will be treated with the Luminor DCB and iVolution stent
Sponsors
ID3 Medical
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
General inclusion criteria: * Patient presenting a score from 2 to 5 following Rutherford classification * Patient is willing to comply with specified follow-up evaluations at the specified times * Patient is \>18 years old * Patient understands the nature of the procedure and provides written informed consent, prior to enrolment in the study * Patient has a projected life expectancy of at least 12 months * Prior to enrolment, the guidewire has crossed target lesion * Patient is eligible for treatment with the Luminor Paclitaxel-Eluting Peripheral Balloon Dilatation Catheter and the iVolution stent * Male, infertile female or female of child bearing potential practicing an acceptable method of birth control with a negative pregnancy test within 7 days prior to study procedure Angiographic inclusion criteria * De novo and post-percutaneous transluminal angioplasty (PTA) restenotic lesions located in the femoropopliteal arteries suitable for endovascular therapy * The target lesion is located within the native femoropopliteal artery * The length of the target lesion is ≥ 150mm and considered as TASC C or D lesion according to the TASC II classification. * The target lesion has angiographic evidence of stenosis \> 50% or occlusion which can be passed with standard guidewire manipulation * Target vessel diameter visually estimated is \>4mm and \<6.5 mm * There is angiographic evidence of at least one-vessel-runoff to the foot, irrespective of whether or not outflow was re-established by means of previous endovascular intervention
Exclusion criteria
* Patient refusing treatment * Presence of a stent in the target lesion that was placed during a previous procedure * Untreated flow-limiting inflow lesions * Any previous surgery in the target vessel (including prior ipsilateral crural bypass) * Patients for whom antiplatelet therapy, anticoagulants or thrombolytic drugs are contraindicated * Patients who exhibit persistent acute intraluminal thrombus of the proposed lesion site * Perforation at the angioplasty site evidenced by extravasation of contrast medium * Patients with known hypersensitivity to heparin, including those patients who have had a previous incidence of heparin-induced thrombocytopenia (HIT) type II * Patients with uncorrected bleeding disorders * Aneurysm located at the level of the superficial femoral artery/popliteal artery * Non-atherosclerotic disease resulting in occlusion (e.g. embolism, Buerger's disease, vasculitis) * Severe medical comorbidities (severe chronic obstructive pulmonary disease, metastatic malignancy, dementia, etc.) or other medical condition that would preclude compliance with the study protocol or 1-year life expectancy * Major distal amputation (above the transmetatarsal) in the study limb or non-study limb * Septicemia or bacteremia * Use of thrombectomy, atherectomy or laser devices during procedure * Any patient considered to be hemodynamically unstable at onset of procedure * Known allergy to contrast media that cannot be adequately pre-medicated prior to the study procedure
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Freedom From Clinically-driven TLR at 12 Months | 12-month | Freedom from clinically-driven TLR at 12 months: defined as a repeated intervention to maintain or re-establish patency within the region of the treated arterial vessel plus 5mm proximal and distal to the treated lesion edge at the respective time points |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Primary Patency Rate | 6 and 12 months post-procedure | Primary patency rate at 6-,12-month follow-up; defined as absence of a hemodynamically significant stenosis on duplex ultrasound (systolic velocity ratio no greater than 2.5) at the target lesion and without TLR within the time of procedure and the given follow-ups |
| Technical Success | Index procedure | Technical success: defined as the ability to cross and dilate the lesion and achieve residual angiographic stenosis no greater than 30% |
| Freedom From Clinically-driven TLR | 6, 24, 36, 48 and 60 months post-procedure | Freedom from clinically-driven Target Lesion Revascularisation (CD-TLR) at 6-month, 2-, 3-, 4- and 5-year follow-up; TLR defined as a repeated intervention to maintain or re-establish patency within the region of the treated arterial vessel plus 5mm proximal and distal to the treated lesion edge at the respective time points |
| Clinical Success | 1, 6, 12, 24, 36, 48 and 60 months post-procedure | Clinical success at follow-up is defined as an improvement of Rutherford classification at 1-, 6-, 12-, 24-, 36-, 48- and 60-month follow-up of one class or more as compared to the pre-procedure Rutherford classification. |
| Serious Adverse Events (SAEs) | up to 60 months post-procedure | Serious adverse events as defined per ISO 14155:2011 |
Countries
Belgium
Participant flow
Recruitment details
A total of 100 study subjects were enrolled in a period of 14 months, between September 2017 and October 2018.
Pre-assignment details
All enrolled patients were treated with the study device.
Participants by arm
| Arm | Count |
|---|---|
| Combination Therapy DCB + Stent Patients treated with the Luminor DCB and the iVolution stent
Combination therapy DCB + stent: Patients will be treated with the Luminor DCB and iVolution stent | 100 |
| Total | 100 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 39 |
| Overall Study | Lost to Follow-up | 9 |
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | Combination Therapy DCB + Stent | — |
|---|---|---|
| Age, Continuous | 73.5 years STANDARD_DEVIATION 9.4 | — |
| Diabetes | 37 Participants | — |
| History of cerebrovascular intervention | 3 Participants | — |
| History of coronary intervention | 23 Participants | — |
| History of peripheral artery intervention | 40 Participants | — |
| Hypercholesterolemia | 63 Participants | — |
| Hypertension | 73 Participants | — |
| Nicotine abuse current | 48 Participants | — |
| Nicotine abuse Former | 22 Participants | — |
| Nicotine abuse never | 30 Participants | — |
| Obesity | 32 Participants | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Region of Enrollment Belgium | 100 Participants | — |
| Sex: Female, Male Female | 33 Participants | — |
| Sex: Female, Male Male | 67 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 39 / 100 |
| other Total, other adverse events | 44 / 100 |
| serious Total, serious adverse events | 80 / 100 |
Outcome results
Primary
Freedom From Clinically-driven TLR at 12 Months
Freedom from clinically-driven TLR at 12 months: defined as a repeated intervention to maintain or re-establish patency within the region of the treated arterial vessel plus 5mm proximal and distal to the treated lesion edge at the respective time points
Time frame: 12-month
Population: At twelve month, 5 patients had a TLR, 7 patients died, 1 withdrew his consent and 1 patient was lost-to-follow-up
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Combination Therapy DCB + Stent | Freedom From Clinically-driven TLR at 12 Months | 5 participants |
Secondary
Clinical Success
Clinical success at follow-up is defined as an improvement of Rutherford classification at 1-, 6-, 12-, 24-, 36-, 48- and 60-month follow-up of one class or more as compared to the pre-procedure Rutherford classification.
Time frame: 1, 6, 12, 24, 36, 48 and 60 months post-procedure
Population: Not all patients had a 1 to 60-month follow-up (e.g. missed visits, patients died, lost-to follow-up, ....) . As a result, not all 100 rutherford measurements were available for each visit.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Combination Therapy DCB + Stent | Clinical Success | Number of patients whose RCC was improved compared to baseline at 1-month follow-up. | 84 Participants |
| Combination Therapy DCB + Stent | Clinical Success | Number of patients whose RCC was improved compared to baseline at 6-month follow-up. | 79 Participants |
| Combination Therapy DCB + Stent | Clinical Success | Number of patients whose RCC was improved compared to baseline at 12-month follow-up. | 74 Participants |
| Combination Therapy DCB + Stent | Clinical Success | Number of patients whose RCC was improved compared to baseline at 24-month follow-up. | 56 Participants |
| Combination Therapy DCB + Stent | Clinical Success | Number of patients whose RCC was improved compared to baseline at 36-month follow-up. | 47 Participants |
| Combination Therapy DCB + Stent | Clinical Success | Number of patients whose RCC was improved compared to baseline at 60-month follow-up. | 25 Participants |
| Combination Therapy DCB + Stent | Clinical Success | Number of patients whose RCC was improved compared to baseline at 48-month follow-up. | 39 Participants |
Secondary
Freedom From Clinically-driven TLR
Freedom from clinically-driven Target Lesion Revascularisation (CD-TLR) at 6-month, 2-, 3-, 4- and 5-year follow-up; TLR defined as a repeated intervention to maintain or re-establish patency within the region of the treated arterial vessel plus 5mm proximal and distal to the treated lesion edge at the respective time points
Time frame: 6, 24, 36, 48 and 60 months post-procedure
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Combination Therapy DCB + Stent | Freedom From Clinically-driven TLR | Number of patients with CD-TLR at 4 years | 20 participants |
| Combination Therapy DCB + Stent | Freedom From Clinically-driven TLR | Number of patients with CD-TLR at 6 months | 1 participants |
| Combination Therapy DCB + Stent | Freedom From Clinically-driven TLR | Number of patients with CD-TLR at 2 years | 10 participants |
| Combination Therapy DCB + Stent | Freedom From Clinically-driven TLR | Number of patients with CD-TLR at 3 years | 17 participants |
| Combination Therapy DCB + Stent | Freedom From Clinically-driven TLR | Number of patients with CD-TLR at 5 years | 25 participants |
Secondary
Primary Patency Rate
Primary patency rate at 6-,12-month follow-up; defined as absence of a hemodynamically significant stenosis on duplex ultrasound (systolic velocity ratio no greater than 2.5) at the target lesion and without TLR within the time of procedure and the given follow-ups
Time frame: 6 and 12 months post-procedure
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Combination Therapy DCB + Stent | Primary Patency Rate | Number of patient who lost their Primary patency at 6 months | 7 participants |
| Combination Therapy DCB + Stent | Primary Patency Rate | Number of patient who lost their Primary patency at 12 months | 8 participants |
Secondary
Serious Adverse Events (SAEs)
Serious adverse events as defined per ISO 14155:2011
Time frame: up to 60 months post-procedure
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Combination Therapy DCB + Stent | Serious Adverse Events (SAEs) | 226 serious adverse events |
Secondary
Technical Success
Technical success: defined as the ability to cross and dilate the lesion and achieve residual angiographic stenosis no greater than 30%
Time frame: Index procedure
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Combination Therapy DCB + Stent | Technical Success | 100 Participants |