The DES BTK Vascular Stent System vs PTA in Subjects With Critical Limb Ischemia

A Randomized Trial Comparing the Drug-Eluting Stent (DES) Below-the-Knee (BTK) Vascular Stent System (DES BTK Vascular Stent System) vs Percutaneous Transluminal Angioplasty (PTA) Treating Infrapopliteal Lesions in Subjects With Critical Limb Ischemia

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03551496

Acronym

SAVAL

Enrollment

201

Registered

2018-06-11

Start date

2018-08-31

Completion date

2023-12-20

Last updated

2024-07-01

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Critical Limb Ischemia

Brief summary

Single phased global, prospective, multicenter clinical trial designed to demonstrate a superior patency rate and acceptable safety in below the knee arteries with lesions treated with the DES BTK Vascular Stent System vs. percutaneous transluminal angioplasty (PTA).

Detailed description

A global, prospective, multicenter, 2:1 randomized trial evaluating the safety and effectiveness of the DES BTK Vascular Stent System compared to standard percutaneous transluminal angioplasty to treat infrapopliteal artery lesions in subjects with critical limb ischemia(CLI). Approximately 201 subjects will be randomized/enrolled to support a 2:1 randomization.

Interventions

COMBINATION_PRODUCTDrug Eluting Stent - Below the Knee

Treatment arm with DES-BTK, starting with one size of the device - 3.5 mm X 80 mm

DEVICEStandard PTA Control Arm

The PTA device used must be market-released in the investigational center's geography and the size (ie, diameter, balloon length and catheter length) will be determined by the investigator.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

SINGLE (Outcomes Assessor)

Masking description

A review of the wound assessment data will be completed by independent reviewer(s) who will be blinded to the randomized therapy.

Intervention model description

Approximately 201 subjects will be randomized in a 2:1 fashion for phase A RCT. Randomizations will be stratified by investigational center and lesion length with 2 subjects receiving the DES BTK for every 1 subject receiving treatment with standard PTA.

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

1. Subject is 18 years or older and has signed and dated the trial informed consent form (ICF) 2. Subject is willing and able to comply with the trial testing, procedures and follow-up schedule 3. Subject has chronic, symptomatic lower limb ischemia, determined by Rutherford categories 4 or 5 in the target limb, with wound(s) confined to toes/forefoot 4. Subject is a male or non-pregnant female. If female of child-bearing potential, and if sexually active must be using, or agree to use, a medically-acceptable method of birth control as confirmed by the investigator Intra-procedure Inclusion Criteria: 1. Stenotic, restenotic or occlusive target lesion(s) located in the tibioperoneal trunk, anterior tibial, posterior tibial and/or peroneal artery(ies). 2. Target lesion(s) must be at least 4cm above the ankle joint 3. A single target lesion per vessel, in up to 2 vessels, in a single limb 4. Degree of stenosis ≥ 70% by visual angiographic assessment 5. Reference vessel diameter is between 2.5 - 3.25mm for phase A RCT 6. Total target lesion length (or series of lesion segments) to be treated is ≤ 70 mm for phase A RCT prior to the data monitoring committee's approval for stent overlap. (Note: Lesion segment(s) must be fully covered with one DES BTK stent, if randomized to stent) 7. Total target lesion length (or series of lesion segments) to be treated is ≤ 140 mm for phase A RCT after the data monitoring committee's approval for stent overlap (Note: Lesion segment(s) must be fully covered with up to two DES BTK stents, if randomized to stent) 8. Target vessel(s) reconstitute(s) at or above the stenting limit zone (4cm above the ankle joint) 9. Target lesion(s) is located in an area that may be stented without blocking access to patent main branches 10. Treatment of all above the knee inflow lesion(s) is successful prior to treatment of the target lesion 11. Guidewire has successfully crossed the target lesion(s)

Exclusion criteria

1. Life expectancy ≤ 1year 2. Stroke ≤ 90 days prior to the procedure date 3. Prior or planned major amputation in the target limb 4. Previous surgery in the target vessel(s) (including prior ipsilateral crural bypass) 5. Previously implanted stent in the target vessel(s) 6. Failed PTA of target lesion/vessel ≤ 60 days prior to the procedure date 7. Renal failure as measured by a GFR ≤ 30ml/min per 1.73m2, measured ≤ 30 days prior to the procedure date 8. Subject has a platelet count ≤ 50 or ≥ 600 X 103/µL ≤ 30 days prior to the procedure date 9. NYHA class IV heart failure 10. Subject has symptomatic coronary artery disease (ie, unstable angina) 11. History of myocardial infarction or thrombolysis ≤ 90 days prior to the procedure date 12. Non-atherosclerotic disease resulting in occlusion (eg, embolism, Buerger's disease, vasculitis) 13. Subject is currently taking Canagliflozin 14. Body Mass Index (BMI) \<18 15. Active septicemia or bacteremia 16. Coagulation disorder, including hypercoagulability 17. Contraindication to anticoagulation or antiplatelet therapy 18. Known allergies to stent or stent components 19. Known allergy to contrast media that cannot be adequately pre-medicated prior to the interventional procedure 20. Known hypersensitivity to heparin 21. Subject is on a high dose of steroids or is on immunosuppressive therapy 22. Subject is currently participating, or plans to participate in, another investigational trial that may confound the results of this trial (unless written approval is received from the Boston Scientific study team) Intra-procedure

Design outcomes

Primary

Measure	Time frame	Description
Number of Participants With Primary Patency	12 months	Twelve-Month Primary Patency defined as a binary endpoint to be determined via duplex ultrasound (DUS) measuring flow at the 12-month follow-up visit, in the absence of clinically-driven target lesion revascularization (TLR) or bypass of the target lesion. Data table consists of the number of participants with flow as assessed by DUS.
Number of Participants Free From Major Adverse Events (MAE)	12 months	The primary safety endpoint assesses freedom from major adverse events (MAE) at 12 months post-procedure. (MAE is defined as: above ankle amputation in index limb; major re-intervention; and perioperative (30 day) mortality)

Other

Measure	Time frame	Description
Number of Participants With Major Amputation (Defined as Amputation of the Lower Limb at the Ankle Level or Above)	12 months post procedure	Rates of amputation of the lower limb at the ankle level or above
Participant Quality-of-Life Changes Via EuroQol 5 Dimension (EQ-5D) Questionnaire.	12 months post procedure	The EQ-5D is a descriptive system of health-related quality-of-life states consisting of 5 dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) each of which can take 1 of 5 responses. The responses record 5 levels of severity (no problems/slight problems/moderate problems/severe problems/extreme problems) within a particular EQ-5D dimension). The levels are assigned a numeric code 1-5 (eg, 1= no problems and 5= extreme problems).
Participant Quality-of-Life Changes Via Vascular Quality of Life (VascuQol) Questionnaire.	12 months post procedure	Changes in quality of life is measured using the Vascular Quality of Life (VascuQol) questionnaire, which is a 25 item questionnaire used to measure the quality-of-life in patients with lower limb ischemia. The tool is sub-divided into 5 domains: pain, symptoms, activities, social and emotional.
Number of Participants With Baseline Wounds Assessed as Healed	12 months post procedure	Wounds assessed for healed status by Independent Wound Assessors, blinded to randomized treatment.
Number of Participants With Assisted Primary Patency	12 months post procedure	Assisted primary patency defined as the percentage (%) of lesions without clinically-driven TLR and those with clinically-driven TLR (not due to complete occlusion or by-pass) which show flow by DUS without restenosis.
Number of Participants With Major, Serious, Non-serious, Unanticipated, Device-related and Procedure-related Adverse Events	12 months post procedure	Adverse events (AEs) to be classified as major (defined as above ankle amputation of the index limb, major re-intervention (new bypass graft, jump/interposition graft, or thrombectomy/thrombolysis) and perioperative (30 day) mortality), serious, non-serious, unanticipated, procedure-related and device-related.
Number of Participants Who Were Admitted to the Hospital Within 30 Days After the Index Procedure.	Up to 30 days post procedure	Hospitalizations related to Critical Limb Ischemia (CLI) due to target lesion revascularization (TLR)/target vessel revascularization (TVR) or Target Limb Major Amputation or Procedure/Device related Adverse Events
Number of Participants With Hemodynamic Improvement	12 months post procedure	Hemodynamic improvement is defined as improvement of ankle-brachial index (ABI) by ≥0.10 or to an ABI ≥0.90 as compared to pre-procedure value without the need for repeat revascularization.
Number of Participants With Rate of Primary Sustained Clinical Improvement as Assessed by Changes in Rutherford Classification From Baseline	12 months post procedure	Endpoint determined to be a success when there is an improvement in Rutherford Classification of one or more categories as compared to pre-procedure without the need for repeat TLR. Rutherford Classifications: i. Category 0 - Asymptomatic ii. Category 1 - Mild claudication iii. Category 2 - Moderate claudication iv. Category 3 - Severe claudication v. Category 4 - Ischemic rest pain vi. Category 5 - Minor tissue loss - nonhealing ulcer, focal gangrene vii. Category 6 - Major tissue loss - extending above transmetatarsal (TM) level
Number of Participants With Clinically Driven Target Lesion Revascularization	12 months post procedure	Clinically-driven target lesion revascularization is defined as any surgical or percutaneous intervention to the target lesion after the index procedure if: 1. Occurring within 5mm proximal or distal to the original treatment segment with diameter stenosis ≥50% by quantitative angiography and if participant has recurrent symptoms OR 2. In-lesion diameter stenosis less than 50% might also be considered a MAE by the CEC if the subject has recurrent symptoms. Recurrent symptoms are defined as having ≥ 1 change in Rutherford Classification or associated with decreased ABI/TBI of ≥20% or ≥ 0.15 in the treated segment.

Countries

Belgium, France, Japan, Netherlands, United States

Participant flow

Pre-assignment details

Of 201 enrolled participants, 201 met inclusion criteria and were randomized. Phase 2 was not conducted.

Participants by arm

Arm	Count
DES BTK Treatment with DES BTK Drug Eluting Stent - Below the Knee: Treatment arm with DES-BTK, starting with one size of the device - 3.5 mm X 80 mm	130
Conventional PTA Treatment with standard PTA Standard PTA Control Arm: The PTA device used must be market-released in the investigational center's geography and the size (ie, diameter, balloon length and catheter length) will be determined by the investigator.	71
Total	201

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Death	11	7
Overall Study	Other Reasons	1	0
Overall Study	Withdrawal by Subject	4	3

Baseline characteristics

Characteristic	Total	Conventional PTA	DES BTK
Age, Customized Age (Year)	73.02 Years STANDARD_DEVIATION 9.78	72.58 Years STANDARD_DEVIATION 10.14	73.27 Years STANDARD_DEVIATION 9.61
Cardiac History History of Congestive Heart Failure	45 Participants	15 Participants	30 Participants
Cardiac History History of Coronary Artery Disease	115 Participants	40 Participants	75 Participants
Cardiac History History of Myocardial Infarction (MI)	42 Participants	13 Participants	29 Participants
Current Anginal Status None	170 Participants	62 Participants	108 Participants
Current Anginal Status Stable Angina	31 Participants	9 Participants	22 Participants
Current Anginal Status Unknown	0 Participants	0 Participants	0 Participants
Current Anginal Status Unstable Angina	0 Participants	0 Participants	0 Participants
Current Diabetes Mellitus	134 Participants	47 Participants	87 Participants
History of amputation	44 Participants	16 Participants	28 Participants
History of amputation - Limb treated Both	5 Participants	3 Participants	2 Participants
History of amputation - Limb treated Non-Target Limb	25 Participants	9 Participants	16 Participants
History of amputation - Limb treated Target Limb	14 Participants	4 Participants	10 Participants
History of amputation - Type of amputation Major	10 Participants	4 Participants	6 Participants
History of amputation - Type of amputation Minor	36 Participants	13 Participants	23 Participants
History of Chronic Obstructive Pulmonary Disease	29 Participants	9 Participants	20 Participants
History of Coronary Artery Bypass Graft (CABG) Surgery	45 Participants	14 Participants	31 Participants
History of Hyperlipidemia requiring medication	153 Participants	52 Participants	101 Participants
History of Hypertension requiring medication	174 Participants	59 Participants	115 Participants
History of interventions with paclitaxel-containing devices	88 Participants	29 Participants	59 Participants
History of other peripheral endovascular interventions with non-paclitaxel containing devices	119 Participants	37 Participants	82 Participants
History of other peripheral endovascular interventions with non-paclitaxel devices - Limb treated Both	26 Participants	8 Participants	18 Participants
History of other peripheral endovascular interventions with non-paclitaxel devices - Limb treated Non-Target Limb	45 Participants	18 Participants	27 Participants
History of other peripheral endovascular interventions with non-paclitaxel devices - Limb treated Target Limb	48 Participants	11 Participants	37 Participants
History of other peripheral endovascular with non-paclitaxel device-Type of most recent intervention Atherectomy	52 Participants	15 Participants	37 Participants
History of other peripheral endovascular with non-paclitaxel device-Type of most recent intervention Other	6 Participants	3 Participants	3 Participants
History of other peripheral endovascular with non-paclitaxel device-Type of most recent intervention Percutaneous Transluminal Angioplasty (PTA)	93 Participants	27 Participants	66 Participants
History of other peripheral endovascular with non-paclitaxel device-Type of most recent intervention Stenting	50 Participants	15 Participants	35 Participants
History of other peripheral vascular surgery	25 Participants	11 Participants	14 Participants
History of other peripheral vascular surgery - Limb Treated Both	1 Participants	0 Participants	1 Participants
History of other peripheral vascular surgery - Limb Treated Non-Target Limb	16 Participants	7 Participants	9 Participants
History of other peripheral vascular surgery - Limb Treated Target Limb	8 Participants	4 Participants	4 Participants
History of Percutaneous Coronary Intervention (PCI)	66 Participants	22 Participants	44 Participants
Neurologic/Renal History History of Cerebrovascular Accident (CVA)	28 Participants	11 Participants	17 Participants
Neurologic/Renal History History of Renal Insufficiency	34 Participants	11 Participants	23 Participants
Neurologic/Renal History History of Renal Percutaneous Intervention	3 Participants	0 Participants	3 Participants
Neurologic/Renal History History of Transient Ischemic Attacks (TIA)	11 Participants	3 Participants	8 Participants
Race/Ethnicity, Customized Race/Ethnicity American Indian or Alaska Native	2 Participants	1 Participants	1 Participants
Race/Ethnicity, Customized Race/Ethnicity Asian	51 Participants	18 Participants	33 Participants
Race/Ethnicity, Customized Race/Ethnicity Black, of African heritage	25 Participants	10 Participants	15 Participants
Race/Ethnicity, Customized Race/Ethnicity Caucasian	104 Participants	35 Participants	69 Participants
Race/Ethnicity, Customized Race/Ethnicity Hispanic or Latino	11 Participants	4 Participants	7 Participants
Race/Ethnicity, Customized Race/Ethnicity Native Hawaiian or other Pacific Islander	0 Participants	0 Participants	0 Participants
Race/Ethnicity, Customized Race/Ethnicity Not Disclosed	5 Participants	2 Participants	3 Participants
Race/Ethnicity, Customized Race/Ethnicity Other	3 Participants	1 Participants	2 Participants
Region of Enrollment Europe	26 Participants	9 Participants	17 Participants
Region of Enrollment Japan	50 Participants	17 Participants	33 Participants
Region of Enrollment United States	125 Participants	45 Participants	80 Participants
Sex: Female, Male Female	51 Participants	16 Participants	35 Participants
Sex: Female, Male Male	150 Participants	55 Participants	95 Participants
Smoking Current	45 Participants	18 Participants	27 Participants
Smoking Never	54 Participants	18 Participants	36 Participants
Smoking Previous	101 Participants	35 Participants	66 Participants
Smoking Unknown	1 Participants	0 Participants	1 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	11 / 130	7 / 71
other Total, other adverse events	84 / 130	37 / 71
serious Total, serious adverse events	82 / 130	51 / 71

Outcome results

Primary

Number of Participants Free From Major Adverse Events (MAE)

The primary safety endpoint assesses freedom from major adverse events (MAE) at 12 months post-procedure. (MAE is defined as: above ankle amputation in index limb; major re-intervention; and perioperative (30 day) mortality)

Time frame: 12 months

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
DES BTK	Number of Participants Free From Major Adverse Events (MAE)	109 Participants
Conventional PTA	Number of Participants Free From Major Adverse Events (MAE)	61 Participants

Primary

Number of Participants With Primary Patency

Twelve-Month Primary Patency defined as a binary endpoint to be determined via duplex ultrasound (DUS) measuring flow at the 12-month follow-up visit, in the absence of clinically-driven target lesion revascularization (TLR) or bypass of the target lesion. Data table consists of the number of participants with flow as assessed by DUS.

Time frame: 12 months

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
DES BTK	Number of Participants With Primary Patency	70 Participants
Conventional PTA	Number of Participants With Primary Patency	38 Participants

Other Pre-specified

Number of Participants Who Were Admitted to the Hospital Within 30 Days After the Index Procedure.

Hospitalizations related to Critical Limb Ischemia (CLI) due to target lesion revascularization (TLR)/target vessel revascularization (TVR) or Target Limb Major Amputation or Procedure/Device related Adverse Events

Time frame: Up to 30 days post procedure

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
DES BTK	Number of Participants Who Were Admitted to the Hospital Within 30 Days After the Index Procedure.	2 Participants
Conventional PTA	Number of Participants Who Were Admitted to the Hospital Within 30 Days After the Index Procedure.	3 Participants

Other Pre-specified

Number of Participants With Assisted Primary Patency

Assisted primary patency defined as the percentage (%) of lesions without clinically-driven TLR and those with clinically-driven TLR (not due to complete occlusion or by-pass) which show flow by DUS without restenosis.