NCT03551496: SAVAL

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

Completed Phase 3 Results posted Last updated 1 July 2024

What this trial tests

Phase 3 trial testing Drug Eluting Stent - Below the Knee in Critical Limb Ischemia in 201 participants. Completed in 20 December 2023.

Timeline

31 August 2018

Primary endpoint
21 April 2022

20 December 2023

Quick facts

Lead sponsor	Boston Scientific Corporation
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	single
Primary purpose	treatment
Enrollment	201
Start date	31 August 2018
Primary completion	21 April 2022
Estimated completion	20 December 2023
Sites	42 locations across France, Japan, Netherlands, Belgium, United States

Drugs / interventions tested

• Drug Eluting Stent - Below the Knee
• Standard PTA Control Arm

Conditions studied

• Critical Limb Ischemia — all drugs for Critical Limb Ischemia →

Sponsor

Boston Scientific Corporation — full company profile →

Who can join

18 and older, any sex, with Critical Limb Ischemia. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants With Primary Patency Primary · 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.

Group	Value	95% CI
DES BTK	70
Conventional PTA	38

Number of Participants Free From Major Adverse Events (MAE) Primary · 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)

Group	Value	95% CI
DES BTK	109
Conventional PTA	61

Number of Participants With Assisted Primary Patency Secondary · 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.

Group	Value	95% CI
DES BTK	75
Conventional PTA	41

Number of Participants With Clinically Driven Target Lesion Revascularization Secondary · 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 i

Group	Value	95% CI
DES BTK	21
Conventional PTA	10

Number of Participants With Major Amputation (Defined as Amputation of the Lower Limb at the Ankle Level or Above) Secondary · 12 months post procedure

Rates of amputation of the lower limb at the ankle level or above

Group	Value	95% CI
DES BTK	3
Conventional PTA	1

Participant Quality-of-Life Changes Via EuroQol 5 Dimension (EQ-5D) Questionnaire. Secondary · 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).

Mobility Improvement

Group	Value	95% CI
DES BTK	40
Conventional PTA	16

Self-Care Improvement

Group	Value	95% CI
DES BTK	19
Conventional PTA	8

Usual Activities Improvement

Group	Value	95% CI
DES BTK	32
Conventional PTA	17

Pain/Discomfort Improvement

Group	Value	95% CI
DES BTK	48
Conventional PTA	18

Anxiety/Depression Improvement

Group	Value	95% CI
DES BTK	28
Conventional PTA	12

Participant Quality-of-Life Changes Via Vascular Quality of Life (VascuQol) Questionnaire. Secondary · 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.

Improvement in pain in leg (or foot) when walking

Group	Value	95% CI
DES BTK	61
Conventional PTA	27

Improvement in worried that I might injure my leg

Group	Value	95% CI
DES BTK	42
Conventional PTA	21

Improvement in cold feet have given

Group	Value	95% CI
DES BTK	50
Conventional PTA	26

Improvement in ability to exercise or to play sports

Group	Value	95% CI
DES BTK	56
Conventional PTA	21

Improvement in legs felt tired or weak

Group	Value	95% CI
DES BTK	55
Conventional PTA	26

Improvement in restricted in spending time with friends or relatives

Group	Value	95% CI
DES BTK	44
Conventional PTA	18

Improvement in pain in the foot (or leg) after going to bed at night

Group	Value	95% CI
DES BTK	58
Conventional PTA	31

Improvement in pins and needles or numbness in leg (or foot) have caused

Group	Value	95% CI
DES BTK	53
Conventional PTA	26

Number of Participants With Baseline Wounds Assessed as Healed Secondary · 12 months post procedure

Wounds assessed for healed status by Independent Wound Assessors, blinded to randomized treatment.

Group	Value	95% CI
DES BTK	34
Conventional PTA	15

Number of Participants With Rate of Primary Sustained Clinical Improvement as Assessed by Changes in Rutherford Classification From Baseline Secondary · 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

Group	Value	95% CI
DES BTK	80
Conventional PTA	36

Number of Participants With Major, Serious, Non-serious, Unanticipated, Device-related and Procedure-related Adverse Events Secondary · 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.

Serious

Group	Value	95% CI
DES BTK	82
Conventional PTA	51

Non serious

Group	Value	95% CI
DES BTK	84
Conventional PTA	37

Major

Group	Value	95% CI
DES BTK	10
Conventional PTA	3

Unanticipated

Group	Value	95% CI
DES BTK	0
Conventional PTA	0

Device-Related

Group	Value	95% CI
DES BTK	16
Conventional PTA	6

Procedure-Related

Group	Value	95% CI
DES BTK	21
Conventional PTA	16

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

Group	Value	95% CI
DES BTK	2
Conventional PTA	3

Number of Participants With Hemodynamic Improvement Secondary · 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.

Group	Value	95% CI
DES BTK	59
Conventional PTA	28

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse event data collected through 12 months post-index procedure.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

DES BTK

Serious: 82/130 (63%)

Deaths: 11/130

Conventional PTA

Serious: 51/71 (72%)

Deaths: 7/71

Serious adverse events (153 terms)

Reaction	System	DES BTK	Conventional PTA
Peripheral arterial occlusive disease	Vascular disorders	—	—
Peripheral artery stenosis	Vascular disorders	—	—
Peripheral ischaemia	Vascular disorders	—	—
Osteomyelitis	Infections and infestations	—	—
Peripheral artery occlusion	Vascular disorders	—	—
Gangrene	Infections and infestations	—	—
Intermittent claudication	Vascular disorders	—	—
Cardiac failure congestive	Cardiac disorders	—	—
Pneumonia	Infections and infestations	—	—
Acute kidney injury	Renal and urinary disorders	—	—
Angina pectoris	Cardiac disorders	—	—
Cellulitis	Infections and infestations	—	—
Acute myocardial infarction	Cardiac disorders	—	—
Gastrointestinal haemorrhage	Gastrointestinal disorders	—	—
Impaired healing	General disorders	—	—
Skin ulcer	Skin and subcutaneous tissue disorders	—	—
Anaemia	Blood and lymphatic system disorders	—	—
Peripheral artery thrombosis	Vascular disorders	—	—
Hypotension	Vascular disorders	—	—
Urinary tract infection	Infections and infestations	—	—
Localised infection	Infections and infestations	—	—
Sepsis	Infections and infestations	—	—
Vascular procedure complication	Injury, poisoning and procedural complications	—	—
Cerebrovascular accident	Nervous system disorders	—	—
Diabetic foot	Skin and subcutaneous tissue disorders	—	—

Other adverse events (194 terms — click to expand)

Reaction	System	DES BTK	Conventional PTA
Peripheral artery occlusion	Vascular disorders	—	—
Wound	Injury, poisoning and procedural complications	—	—
Limb injury	Injury, poisoning and procedural complications	—	—
Peripheral venous disease	Vascular disorders	—	—
Pain in extremity	Musculoskeletal and connective tissue disorders	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—
Vascular procedure complication	Injury, poisoning and procedural complications	—	—
Vasospasm	Vascular disorders	—	—
Peripheral arterial occlusive disease	Vascular disorders	—	—
Peripheral ischaemia	Vascular disorders	—	—
Oedema peripheral	General disorders	—	—
Nausea	Gastrointestinal disorders	—	—
Skin ulcer	Skin and subcutaneous tissue disorders	—	—
Contusion	Injury, poisoning and procedural complications	—	—
Intermittent claudication	Vascular disorders	—	—
Hypotension	Vascular disorders	—	—
Arterial spasm	Vascular disorders	—	—
Reperfusion injury	Vascular disorders	—	—
Peripheral artery stenosis	Vascular disorders	—	—
Urinary tract infection	Infections and infestations	—	—
Osteomyelitis	Infections and infestations	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—
Muscle spasms	Musculoskeletal and connective tissue disorders	—	—
Chest pain	General disorders	—	—
Diarrhoea	Gastrointestinal disorders	—	—
Vomiting	Gastrointestinal disorders	—	—
Decubitus ulcer	Skin and subcutaneous tissue disorders	—	—
Acute kidney injury	Renal and urinary disorders	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—
Epistaxis	Respiratory, thoracic and mediastinal disorders	—	—
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	—	—
Fall	Injury, poisoning and procedural complications	—	—
Laceration	Injury, poisoning and procedural complications	—	—
Head injury	Injury, poisoning and procedural complications	—	—
Wound complication	Injury, poisoning and procedural complications	—	—
Haematoma	Vascular disorders	—	—
Hypertension	Vascular disorders	—	—
Cellulitis	Infections and infestations	—	—
Viral upper respiratory tract infection	Infections and infestations	—	—
Pneumonia	Infections and infestations	—	—

Most-reported serious reactions: Peripheral arterial occlusive disease, Peripheral artery stenosis, Peripheral ischaemia, Osteomyelitis, Peripheral artery occlusion, Gangrene, Intermittent claudication, Cardiac failure congestive.

Data from ClinicalTrials.gov NCT03551496 adverse events section.

Sponsor's own description

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).

Publications & conference data

7 peer-reviewed publications reference this trial (live from Europe PMC):

1. Current developments in endovascular therapy of peripheral vascular disease.
   Kokkinidis DG, Armstrong EJ. · · 2020 · cited 28× · PMID 32395311 · DOI 10.21037/jtd.2019.12.130
2. Primary results of the SAVAL randomized trial of a paclitaxel-eluting nitinol stent versus percutaneous transluminal angioplasty in infrapopliteal arteries.
   van Overhagen H, Nakamura M, Geraghty PJ, Rao S, et al · · 2023 · cited 26× · PMID 37844137 · DOI 10.1177/1358863x231199489
3. Update on paclitaxel for femoral-popliteal occlusive disease in the 15 months following a summary level meta-analysis demonstrated increased risk of late mortality and dose response to paclitaxel.
   Schneider PA, Varcoe RL, Secemsky E, Schermerhorn M, et al · · 2021 · cited 20× · PMID 32890719 · DOI 10.1016/j.jvs.2020.07.093
4. Diversity in randomized clinical trials for peripheral artery disease: a systematic review.
   Long C, Williams AO, McGovern AM, Jacobsen CM, et al · · 2024 · cited 5× · PMID 38350973 · DOI 10.1186/s12939-024-02104-8
5. Current Status of and Future Prospects for Drug-Eluting Stents and Scaffolds in Infrapopliteal Arteries.
   Lim E, Varcoe RL. · · 2024 · cited 4× · PMID 38541981 · DOI 10.3390/jcm13061757
6. Comparation of drug-eluting stents and control therapy for the treatment of infrapopliteal artery disease: a Bayesian analysis.
   Li Y, Shen X, Zhuang H. · · 2023 · PMID 37720942 · DOI 10.1097/js9.0000000000000736
7. CIRSE 2022 Book of Abstracts
   · 2022