(2024) 22:324
Sheng et al. BMC Medicine
https://doi.org/10.1186/s12916-024-03545-2

BMC Medicine

RESEARCH

Open AccessOne-year outcomes of a novel venous stentfor symptomatic iliofemoral venous obstruction:
prospective cohort study
Chang Sheng1, Xin‑Wu Lu2, Hong‑Tao Shi3, Lei Zhang4, Sheng‑Yun Wan5, Hong‑Pu Li6, Ke Li7, Sen Shi8,
Zhen‑Jie Liu9, Yu‑Xian Luo10, Guo‑Dong Chen11, Mao‑Rong Liu12, You‑Gen Kang13, Bo Ye14, Kai Yao15,
Pu Yang1,16,17*†, Wei Wang1,16,17*† and on behalf of the Trial Investigators

Abstract
Background A stent with characteristics of a hybrid design may have advantages in improving the patency of symptomatic iliofemoral vein obstruction. This study assessed the safety and effectiveness of the V-Mixtent Venous Stent
in treating symptomatic iliofemoral outflow obstruction.
Methods Eligible patients had a Clinical-Etiologic-Anatomic-Physiologic (CEAP) C classification of ≥ 3 or a Venous
Clinical Severity Score (VCSS) pain score of ≥ 2. The primary safety endpoint was the rate of major adverse events
within 30 days. The primary effectiveness endpoint was the 12-month primary patency rate. Secondary endpoints
included changes in VCSS from baseline to 6 and 12 months, alterations in CEAP C classification, Chronic Venous Disease Quality of Life Questionnaire (CIVIQ-14) scores at 12 months, and stent durability measures.
Results Between December 2020 and November 2021, 171 patients were enrolled across 15 institutions. A totalof 185 endovenous stents were placed, with 91.81% of subjects receiving one stent and 8.19% receiving 2 stents.
Within 30 days, only two major adverse events occurred (1.17%; 95% confidence interval [CI], 0.14–4.16%),
below the literature-defined performance goal of 11% (P < .001). The 12-month primary patency rate (91.36%; 95%
CI, 85.93–95.19%; P < .001) exceeded the literature-defined performance goal. VCSS changes from baseline demonstrated clinical improvement at 6 months (− 4.30 ± 3.66) and 12 months (− 4.98 ± 3.67) (P < .001). Significant reduction
in symptoms, as measured by CEAP C classification and CIVIQ-14, was observed from pre-procedure to 12 months(P < .001).
Conclusions The 12-month outcomes confirm the safety and effectiveness of the V-Mixtent Venous Stent in managing symptomatic iliofemoral venous outflow obstruction, including clinical symptom improvement compared
to before treatment.
Keywords Venous stenting, Iliofemoral venous outflow obstruction, Patency, Multicenter study, Clinical improvement†

Wei Wang and Pu Yang contributed equally to this work.

*Correspondence:
Pu Yangpuyang@csu.edu.cn
Wei Wang
weiwangcsu@csu.edu.cn
Full list of author information is available at the end of the article© The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0
International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as longas you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if
you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article orparts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicatedotherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not
permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To
view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.

Sheng et al. BMC Medicine(2024) 22:324

Background
Deep venous stenting has gained significant popularity
as a prevalent approach for managing acute or chronic
venous obstruction, including non-thrombotic iliac veinlesions (NIVL) in recent years [1, 2]. This is particularly
relevant for individuals classified as Clinical-EtiologicAnatomic-Physiologic (CEAP) C ≥ 3 or with a Venous
Clinical Severity Score (VCSS) score ≥ 2 or both. Patients
falling into these categories, exhibiting over 50% stenosis on imaging modalities such as computed tomography
venography, magnetic resonance venography, intravascular ultrasound, or venography, should be considered
for venous stenting [2]. Similarly, patients with identified
stenotic lesions undergoing thrombus removal for acute
iliofemoral deep vein thrombosis (DVT) should also be
considered eligible candidates for venous stenting [2].
Explorations into venous stenting in pelvic veins commenced in the early 1990s [3–7], with subsequent extensive scrutiny of peer-reviewed publications by Raju in2013 affirming that “Iliac vein stenting is safe, with negligible morbidity (< 1%), and exhibits patency rates of 90%
to 100% for non-thrombotic disease and 74% to 89% for
post-thrombotic disease at 3 to 5 years” [8]. The reported
outcomes spanning short, mid, and long-term periods
over the past 25 years consistently demonstrate promise.
Venous stents, as a whole, have undergone meticulous
design enhancements aimed at improving their effectiveness and facilitating the endovascular treatment of
intricate venous lesions. These advancements include
increased flexibility, expandability, and improved visibility [9]. Despite these improvements, the ongoing challenge lies in striking the optimal balance between radial
force/crush resistance and high flexibility. Consequently,
the selection of a stent should be tailored to suit the specific circumstances, considering factors such as flexibility,
the risk of stent fracture (e.g., when crossing the inguinal ligament), and the imperative for heightened crush
resistance.
In this context, the V-Mixtent Venous Stent (Shanghai
EndoVas Medical Technology Co., Ltd, Shanghai, China),
employing a modular design concept with non-uniform
stents that combine laser-cut and woven structures, presents a promising solution. The objective of this study is
to assess the safety and effectiveness of the V-Mixtent
Venous Stent in the management of iliofemoral venous
outflow obstruction.
Methods
Study design

This research report adheres to the STROCSS standards [10]. This prospective, single-arm multicenter trial
was designed to include adult participants aged ≥ 18
and ≤ 75 years who presented with symptomatic chronic

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non-malignant obstruction of the iliofemoral venous system. The primary objective was to assess the safety andeffectiveness of the V-Mixtent Venous Stent. To ensure
a diverse patient population, the study involved large
medical centers, with efforts directed towards achieving an equitable distribution of enrollments across centers, where each center enrolled ≤ 30% of the total sample.
Consecutive patient screening was employed to minimize
selection bias, and treated venous segments included thecommon iliac vein (CIV), external iliac vein (EIV), andcommon femoral vein (CFV).
The implementation process of the study can be seenin Additional file 1: Fig. S1. The inclusion and exclusion
criteria for the study were detailed in the additional file
(Additional file 1: Table S1). Inclusion criteria necessitated patients to have manifested unilateral and clinically significant venous obstruction, defined as clinicalclassification ≥ C3 of the CEAP classification [11] or a
VCSS score [12] ≥ 2, along with luminal diameter reduction ≥ 50% on biplanar venography. Biplanar venography
involves visualizing the target blood vessel at its maximum and minimum diameters through naked-eye observation. Exclusion criteria included recent pulmonary
embolism, contralateral venous disease, inferior vena
cava involvement, limited life expectancy, known allergy
to stent components, near-term family planning, uncontrolled or active coagulopathy, bleeding diathesis, orplanned concurrent venous procedures within 30 days ofstent implantation. Stenting was indicated for acute DVT
post-thrombectomy or thrombolysis in cases of residual
iliac vein obstruction. Pre-procedure clinical assessments, incorporating CEAP C classification, VCSS, andChronic Venous Insufficiency Questionnaire (CIVIQ-14)[13], were performed.
Between December 2020 and November 2021, a totalof 171 patients underwent implantation at 15 centers in
China. The study has a scheduled follow-up period of 5
years. The study protocol received approval from institutional review boards or ethical committees at participating centers. A Clinical Events Committee (CEC) was
responsible for adjudicating events related to primary
safety and effectiveness endpoints, while a Data and
Safety Monitoring Board oversaw safety outcomes. Image
data will be evaluated by independent core laboratories,
adhering to the principles outlined in the Declaration of
Helsinki. The study obtained approval from the Institutional Review Board at each study center, and all patientsprovided informed consent.
Device description

The V-Mixtent Venous Stent was a self-expanding nitinol
stent featuring radiopaque markers (Fig. 1). We compared
the properties of the V-Mixtent Venous Stent with thoseSheng et al. BMC Medicine(2024) 22:324

Page 3 of 11

Fig. 1 V-Mixtent Venous Stent designof other venous stents (Additional file 1: Table S2). Uniform in diameter, the stent was available in six sizes: 10,
12, 14, 16, 18, and 20 mm. Stent length options included
60, 80, 100, 120, and 150 mm. The stent incorporated
etched segments, which came in three lengths: 37, 47,
and 57mm. It is noteworthy that not all stent lengths
were compatible with the utilization of etched segments.
Preloaded within 8F or 10F over-the-wire introducersof 80-cm lengths, the stent was purpose-designed for
iliofemoral veins. The common iliac vein segment of thestent displayed a laser-etched structure, ensuring robustradial support and local resistance to compression. During surgical procedures, the etched section was released
initially without a rebound effect, ensuring precise positioning and accurate deployment. Additionally, the stent
boasted a woven structure designed to conform to thephysiological curvature of the iliofemoral vein, providing a high degree of flexibility. The weaving pattern facilitated the smooth downward extension of the distal end
upon release, rendering it suitable for placement in tortuous and diametrically varying vessels and enabling joint
crossing. A looped structure was strategically employed
to establish a flexible connection between the etched andweaving sections. Furthermore, all silk tips were embedded within the stent, a feature aimed at minimizing damage to the vessel wall.
Implant procedure

Baseline assessment of percentage diameter stenosis was
conducted using biplanar venography. Stent sizing, placement extent, and evaluation of postprocedural residual
stenosis were guided by venography. The procedure recommended both vessel predilation and post-stent dilatation. The stents were deliberately oversized by 2 to 4
mm in consideration of the surrounding vasculature,
the expanded balloon diameter used for predilation, or
the standard diameter of the vein intended for stenting.

Recommendations included achieving comprehensive
lesion coverage and extending into healthy tissue, bothcaudally and cranially, by 5 to 10 mm. For cases involving multiple stents, a recommended stent overlap of ≥ 1
cm was advised. Post-procedural assessment of lesion
and stent placement characteristics was performed
through two-view venography. Participants underwent
a 12-month standardized anticoagulation regimen poststent implantation, with the specific protocol determinedby the research physician based on the participant’s condition [14]. The main anticoagulant drugs used include
rivaroxaban, edoxaban, argatroban, troxerutin, lowmolecular weight heparin, and unfractionated heparin.
Patient follow‑up

Treatment success was appraised by gauging enhancements in clinical assessment scales (CEAP, VCSS, and
CIVIQ-14) at 6 and 12 months. The evaluation encompassed the assessment of the incidence of stent fracture and clinical migration. Imaging follow-up included
duplex ultrasound at 6 and 12 months to assess stent
flow, two-view venography (or CTA), and radiography
at 12 months for a quantitative appraisal of patency andstent integrity, respectively. Follow-up visits were conducted at 1 month, 6 months, and 1 year to scrutinize
adverse events and investigate antithrombotic measures.
Taking into account the differences in long-term patency
rates between patients with thrombotic and non-thrombotic types after stent implantation [8], we have grouped
the results of this section.
Study definitions

The primary safety endpoint consisted of a composite ofmajor adverse events (MAEs) within 30 days post-procedure, encompassing complications related to the device
or procedure. The primary effectiveness endpoint was
the 12-month primary patency rate, defined as freedomSheng et al. BMC Medicine(2024) 22:324

from occlusion or thrombosis within the target vessel,and freedom from surgical or endovascular intervention
to maintain patency. Technical success signified the successful delivery and deployment of the stent, while procedural success indicated improved flow through the target
lesion (stenosis ≤ 50%) with no MAEs before discharge.
Clinical migration was defined as stent movement requiring intervention (Additional file 1: Table S3) [15, 16].
Statistical analysis

The study design was predicated on power calculations
derived from prior research on dedicated venous stents[15, 17, 18]. Given a sample size of 171 evaluable patients,
the study achieved over 80% power for the primary safety
endpoint, assuming a major adverse event (MAE) rate of
4% and a performance goal of 11%. Similarly, the study
attained over 80% power for the primary effectivenessendpoint, assuming a primary patency of 84% and a performance goal of 74%. Both analyses were conductedusing a two-tailed exact probability method with a significance level of 0.05.
Statistical analyses were performed using SAS for Windows, release 9.4 (SAS Institute, Cary, NC). Continuous
variables are expressed as the mean ± standard deviation,
while categorical variables are presented as counts andpercentages. For patients unable to be observed for the
primary effectiveness endpoint, the worst-case imputation method (WOCF) was employed for imputing the
primary safety assessment endpoint. Regarding the primary effectiveness endpoint, which might encountermissing data due to imaging follow-up, supplementary
clinical indirect effectiveness estimation methods suchas Doppler ultrasound and appropriate data imputation
methods were utilized for sensitivity analysis. These supplementary approaches serve as supportive evidence forthe primary analysis, enhancing the robustness and reliability of the study findings.

Results
Baseline patient characteristics

A total of 171 patients, comprising 73 with primarythrombosis (PT) and 98 with non-thrombotic lesions(NT), from 15 participating sites were deemed eligible and underwent V-Mixtent Venous Stent placement(Additional file 1: Table S4). Baseline demographics andcomorbid medical conditions are presented in Table 1.
The mean age of the patients was 59 ± 9 years, ranging
from 30 to 83 years, and a balanced gender distribution was observed. Common medical histories included
peripheral venous disease (48.54%) and hypertension(33.33%). Further details of baseline venous clinicalassessments are provided in Table 2, revealing that C3

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Table 1 Demographic and preexisting comorbid medical
conditions
Characteristic

Value

Age, years (n = 171)
Mean ± standard deviation

59 ± 9

Range

30–83

Sex
Male patients47.95 (82/171)

Female patients

52.05 (89/171)

BMI, kg/m2 (n = 170)
Mean ± standard deviation

25.33 ± 3.43

Range

18.59–35.56

Medical historyDM

8.77 (15/171)

Type 10 (0/15)Type 2100.00 (15/15)

Hypertension

33.33 (57/171)

Smoking status
Never

85.38 (146/171)

Previous

5.26 (9/171)

Current

9.36 (16/171)

Coronary heart disease

6.43 (11/171)

PE (> 6 months)

2.92 (5/171)

Stroke6.43 (11/171)

Data are presented as mean (SD), percentage (no./No.), unless noted otherwise
BMI body mass index, PE pulmonary embolism, DM diabetes mellitus

Table 2 Baseline venous clinical assessments
Venous assessment

Value

CEAP C classification
C0-2

1.17 (2/171)

C3

44.44 (76/171)

C4a

22.22 (38/171)

C4b

6.43 (11/171)

C5

14.04 (24/171)

C6

11.70 (20/171)

VCSS (n = 171)
Mean ± standard deviation

7.43 ± 4.18

Range

2–21

CIVIQ-14 score (n = 171)
Mean ± standard deviation

26.94 ± 10.97

Range

14–70

Data are presented as mean (SD), percentage (no./No.), unless noted otherwise
CEAP Clinical, Etiological, Anatomical, Pathophysiological, VCSS venous clinicalseverity score, CIVIQ-14 Chronic Venous Disease Quality of Life Questionnaire

had the highest representation in the CEAP C classification, accounting for 44.44%.

Sheng et al. BMC Medicine(2024) 22:324

Procedural results

Details regarding patient indications for stent placement, lesion characteristics, and venographic measurements are outlined in Table 3. The left leg was
the predominant target limb (91.23%, 156/171). The
core laboratory-assessed mean lesion length was
64.59 ± 45.43 mm, and the mean diameter stenosis was
81.33 ± 14.68%, with 13.45% showing total occlusions.
Preimplant dilation was performed in the majorityof stent placements (98.25%, 168/171). Most patients(96.49%, 165/171) exhibited lesions in the common
iliac vein (CIV). A total of 185 endovenous stents wereplaced, with 91.81% (157/171) of subjects receiving one
stent and 8.19% (14/171) receiving 2 stents (Table 3).
Predominantly, the implanted stents (51.89%, 96/185)
were 14 mm in diameter, followed by 33.51% being 16
mm in diameter, and 10.81% being 12 mm in diameter.
The most common stent length was 100 mm. Following stent placement, adjunct balloon dilation was conducted for 66.28% (114/171) of cases. The technicalsuccess rate was 100%. Post-procedure diameter stenosis, as assessed by venography, was 24.29% ± 11.12%(Table 3). The procedural success rate was 99.42%(170/171); one patient experienced thrombotic occlusion within the stent, necessitating secondary intervention before discharge. No contralateral deep veinthrombosis (DVT) events were observed within 12
months. The proportion of patients with postoperative
antithrombotic therapy duration exceeding 6 months
is 85.80% (139/162) [19]. The core laboratory conducted individual diameter stenosis assessments forpatients with available venographic data or Doppler
ultrasound (DUS), which were utilized to evaluate theprimary effectiveness endpoint. A representative subject’s preprocedural and postprocedural venography isdisplayed in Fig. 2.

Page 5 of 11

Table 3 Indication and core laboratory-reported baseline lesion
characteristics and venographic measurements
Characteristic

Value

Study lesion laterality
Left

91.23 (156/171)

Right

8.77 (15/171)

Lesion etiology
PT

42.69 (73/171)

NT

57.31 (98/171)

Access site
Femoral

66.08 (113/171)

Popliteal

31.58 (54/171)

Superficial vein

2.34 (4/171)

Anesthesia type
Local

98.83 (169/171)

General0.58 (1/171)

Spinal0.58 (1/171)

Study lesion ­locationa
CIV

96.49 (165/171)

EIV

18.13 (31/171)

CFV

3.51 (6/171)

Reference vessel diameter, mm (n = 171)
Mean ± standard deviation

13.96 ± 3.03

Range

3.50–31.00

Lesion length, mm (n = 171)
Mean ± standard deviation

64.59 ± 45.43

Range

5.00–247.00

Preimplant dilatation performed

98.25 (168/171)

No. of endovenous stents placed
1

91.81 (157/171)2

8.19 (14/171)

Diameter stenosis, %Before procedure (n = 171)   Mean ± standard deviation

81.23 ± 14.09  Range50.00–100.00

Post-procedure (n = 171)

Safety outcomes

Data for the primary safety endpoint were available forall 171 patients. A total of 2 subjects (1.17%) experienced
major adverse events (MAEs) within 30 days (refer toTable 4). Both patients belonged to the primary thrombosis (PT) group, and these MAEs were clinically driven
reinterventions due to stent thrombosis. The upperbound of the two-sided 95% confidence interval (CI) was
4.16%, which was below the 11% performance goal, signifying the successful achievement of the primary safety
endpoint (P < 0.001).
Over the 1-year follow-up period, among the 171 subjects, 27 (15.79%) reported a total of 40 procedure-related
adverse events (AEs). Eight patients (4.68%) reported
a total of 9 device-related AEs, including 4 cases of   Mean ± standard deviation

24.29 ± 11.12  Range

0.54–49.67

At 12 months (n = 162)   Mean ± standard deviation

31.45 ± 23.58  Range

0.45–100.00

Total occlusion

13.45 (23/171)

Data are presented as mean (SD), percentage (no./No.), unless noted otherwise
PT post-thrombotic, NT non-thrombotic, CIV common iliac vein, EIV external iliac
vein, CFV common femoral veinaLesions could have involved more than one location. Therefore, the number oflesion locations totaled more than the total number of patients enrolled

occasional lumbar discomfort post-surgery, a sensationof soreness and swelling in the lower back, general lower
back pain and discomfort, and left-sided lumbar distension. The remaining cases were related to thrombosis

Sheng et al. BMC Medicine(2024) 22:324

Page 6 of 11

Fig. 2 Preprocedural and postprocedural venography of a patient, with the lesion primarily located in the common iliac vein (CIV). The blackarrows indicate the stent. A Preprocedural venography shows significant collateral circulation. B The patient received one stent implantation,and venography shows disappearance of vascular stenosis and collateral circulation

Table 4 Primary effectiveness and safety end points
Outcomes

Primary cause subgroups
Total, P value

NT

PT

Primary safety failures at 30 days (SS)

1.17 (2/171), < .001

0 (0/98)

2.74 (2/73)

Primary patency at 12 months (PPS)

91.36 (148/162), < .001

97.92 (94/96)

81.82 (54/66)

Primary patency at 12 months (FAS)

86.55 (148/171), < .001

95.92 (94/98)

73.97 (54/73)

Data are presented as percentage (no./No.), unless noted otherwise
FAS full analysis set, PPS per-protocol set, SS safe analysis set, NT non-thrombotic, PT post-thrombotic

within the stent, thrombosis in the left common iliac
vein, exacerbated thrombosis within the stent, and deepvein thrombosis. The occurrence rate of MAEs within 12
months was 5.26% (9/171), and all were clinically driven
reinterventions due to stent thrombosis. Additionally, three patients died: two cases were unrelated to thedevice and procedure, while the cause of death for one
patient was unknown due to loss to follow-up. Importantly, no device defects or bleeding events meeting theMAE definition occurred during the study, emphasizing
the safety profile of the V-Mixtent Venous Stent.
Effectiveness outcomes

In total, 162 out of 171 patients (94.74%) were eligible forthe primary effectiveness endpoint (Fig. 3). Among them,
159 subjects had the imaging component of primarypatency assessed through venogram, while the remaining
3 subjects underwent analysis using Doppler ultrasound(DUS). Nine subjects were excluded from the primarypatency analysis for various reasons: 3 subjects passed
away, 3 were lost to follow-up, and 3 declined further follow-up. Out of the 162 assessable patients, 148 subjects(91.36%) achieved primary patency (refer to Table 4).
The lower limit of the two-sided 95% confidence interval(CI) was 85.93%, surpassing the performance goal of 74%(P < 0.001).
Among the 14 patients who experienced a loss ofpatency during the 12-month follow-up, 12 were primarythrombosis (PT) patients. In this group, two patients
underwent clinically driven target vessel revascularization before the conclusion of the one-year follow-up,
whereas the remaining 12 patients encountered patency
loss by the 1-year follow-up milestone. Sensitivity analyses were performed to evaluate the influence of missing
data on the primary patency endpoint. Even when considering up to 9 missing data points as a loss of primarySheng et al. BMC Medicine(2024) 22:324

Page 7 of 11

Fig. 3 Sankey diagram displayed the population flow in this study. The numbers on the colored ribbons in the figure indicate the included
population. The different lines represent various scenarios of traffic diversion. PT, post-thrombotic; NT, non-thrombotic; PPS, per-protocol set; DUS,
doppler ultrasoundpatency, the results remained consistent with the primary
analysis. Subgroup analyses indicated a primary patencyof 97.92% (94/96) in the non-thrombotic lesions (NT)group and 81.82% (54/66) in the PT group.

Clinical outcomes

Following stent placement, patients reported a progressive reduction in symptoms, evidenced by improvements in three clinical scales at 6 and 12 months (refer

Table 5 Change in Venous Clinical Severity Score (VCSS) and Chronic Venous Disease Quality of Life Questionnaire (CIVIQ-14) frombaseline through 12 months
Baseline (N = 171)

6 months (N = 163), P value

6 months change
from baseline

12 months (N = 162), P value

12 months
change frombaseline

VCSS

7.43 ± 4.18

3.18 ± 3.08, < .001

− 4.30 ± 3.66

2.56 ± 2.95, < .001

− 4.98 ± 3.67

NT

7.92 ± 3.91

3.12 ± 2.63, < .001

− 4.83 ± 3.65

2.43 ± 2.35, < .001

− 5.50 ± 3.78

PT

6.77 ± 4.46

3.27 ± 3.66, < .001

− 3.56 ± 3.56

2.74 ± 3.66, < .001

− 4.30 ± 3.73

CIVIQ-14

26.9 ± 10.97

17.60 ± 6.48, < .001

− 9.50 ± 10.46

16.04 ± 4.58, < .001

− 10.75 ± 11.04

NT

24.72 ± 9.86

16.85 ± 6.34, < .001

− 8.05 ± 9.15

15.60 ± 3.23, < .001

− 9.20 ± 9.87

PT

29.92 ± 11.73

18.70 ± 6.57, < .001

− 12.15 ± 11.92

16.71 ± 6.02, < .001

− 14.03 ± 12.72

Data are presented as mean (SD), unless noted otherwise
P value determined using paired t test
VCSS Venous Clinical Severity Score, CIVIQ-14 Chronic Venous Disease Quality of Life QuestionnaireSheng et al. BMC Medicine(2024) 22:324

to Table 5 and Fig. 4). Out of 162 patients, 138 (85.19%)
experienced symptomatic improvement (VCSS score
improvement ≥ 2 points), leading to a mean VCSS score
decrease from 7.43 ± 4.18 at baseline to 2.56 ± 2.95
at 12 months. Only three patients (1.85%) exhibitedworsened VCSS scores at the 12-month mark. On the
Chronic Venous Insufficiency Questionnaire (CIVIQ14), the mean score decreased from 26.94 ± 10.97 atbaseline to 16.04 ± 4.58 at 12 months. Among the 162
patients, over half (58.02%) reported an improvement in quality of life (QOL), demonstrating at leasta 6-point decrease in CIVIQ-14 score, while four
patients (2.47%) considered themselves worsened at
this time point. A significant correlation between follow-up time points and the CEAP C classification wasobserved (P < 0.001). At 12 months post-procedure, theCEAP C classification improvement rate (C classification improvement ≥ 1) was 66.05%, with 39.51% fallingunder grade C3 or below.
Given these results and recognizing potential differences in safety and effectiveness outcomes between the
non-thrombotic lesions (NT) and primary thrombosis(PT) groups, a subgroup analysis was conducted. The
improvements in CIVIQ-14 scores and VCSS for boththe NT and PT groups at various follow-up time points
are presented in Table 5. Significant differences in
CIVIQ-14 score improvements were observed between
the NT and PT groups at the 6-month (P = 0.018) and
12-month (P = 0.014) follow-up periods.

Page 8 of 11

Discussion
This report presents the outcomes of a prospective multicenter feasibility study evaluating a specialized venous
stent. The study highlights a noteworthy 12-monthpatency rate and minimal safety concerns, emphasizing
the positive impact of the intervention on clinical outcomes. Comprehensive assessments, including CEAP,
VCSS, and CIVIQ-14, indicate significant improvements.
Despite challenges in measuring improvements overtime without a control dataset and accounting for factors
such as patient selection and disease state variations, thestudy surpassed predefined pretrial performance benchmarks for primary safety and effectiveness rates. This
underscores the potential benefits of the stent’s uniquedesign, combining etched and braided structures. Further research is essential to deepen our understanding ofthese promising outcomes and explore the stent’s potential applications.
Prospective multicenter studies offer a higher degreeof representativeness in assessing therapeutic intervention outcomes compared to single-center or retrospective analyses. Despite inherent differences, the clinicaland morphological outcomes of the presented study alignwith prior commendable reports on venous stenting[15, 16, 20–22]. The consistency in results across various studies reinforces the significance of interventional
treatments for individuals grappling with symptomatic
iliofemoral obstructive venous disease. Notably, the30-day freedom from MAE in the VIRTUS [15] and VERNACULAR [22] studies was substantial, recording rates

Fig. 4 Change in Clinical, Etiological, Anatomical, Pathophysiological (CEAP) C classification from baseline through 12 months

Sheng et al. BMC Medicine(2024) 22:324

of 98.8% and 93.5%, respectively. It is essential to notethat the VIRTUS and VERNACULAR trials predominantly included patients with chronic venous disease,
excluding those with acute DVT [15, 22]. This selective
approach, while potentially optimizing candidates forstent placement, differs from earlier research that validated the safety of stenting in patients after thrombus
removal [23]. Additionally, the VIVO study [16] accurately represented a real-world population, and the ABRE
study [21] featured a population most akin to that of the
VIVO study, encompassing acute DVT, post-thrombotic
syndrome, and NIVLs. The corresponding 12-month primary patency outcomes across these studies ranged from
84.0% (VIRTUS study), 88.6% (VERNACULAR study),
89.9% (VIVO study), to 88.0% (ABRE study).
Distinct etiologies of iliofemoral lesions, particularly
chronic PT conditions, have been linked to worse outcomes compared to non-thrombotic (NT) or acute DVT
cases [20, 24]. In the VIRTUS trial, primary patency wasnotably higher in NT cases (96.2%) compared to chronic
PT cases (79.8%), averaging at 84% for the overall cohort[15]. Nevertheless, providing treatment to patients in
the PT group proves valuable, supported by substantial enhancements in Quality of Life (QOL). Consistent with this pattern, the current study demonstrates
higher patency in NT patients. Additionally, an interesting observation in this study is that, at both follow-up
time points, the improvement in CIVIQ-14 scores in the
PT group was significantly higher than that in the NT
group. This difference could be attributed to the higher
baseline CIVIQ-14 scores in the PT group. Typically,
patients with NIVLs exhibit shorter lesions, leading toenhanced primary patency due to the compact, segmental nature of their lesions and the normal status of their
inflow and outflow veins [15, 21, 22]. However, whether
there exists a clinically significant difference in patency
outcomes between patients with acute DVT or thosewith chronic post-thrombotic disease requires further
clarification. Findings from a large retrospective study
suggested higher patency rates for patients with chronic
post-thrombotic disease [25], while the ABRE study indicated superior patency rates for patients with acute DVT[21]. More extensive data comparing stent patency after
treating post-thrombotic disease or following acute DVT
removal are necessary to comprehensively understandand characterize the nuances in outcomes based on different etiologies of iliofemoral lesions.
Throughout the 12-month follow-up period of thisstudy, no occurrences of stent migration or integrity
damage were observed. We also know that the currently
used stents (Abre, Venovo, and Wallstent) have a very low
risk of stent fractures associated with crossing the inguinal ligament. It is essential to note, however, that prior

Page 9 of 11

studies have documented instances of stent fracturesand migrations [15, 16]. Stent migration in the venous
system is a rare but potentially consequential complication that could necessitate open surgery. Mitigating therisk of stent migration involves implementing thoroughtraining programs, employing appropriate stent selection
practices, ensuring excellent procedural techniques, andmaintaining a dedicated follow-up program [26–28].
Our study has several limitations. While outcomes invenous stenting have consistently shown promise, thelevel of supporting evidence remains modest due to a lackof controlled prospective trials scrutinizing performanceand safety aspects. Due to the heterogeneity between
research centers, there may be potential adverse biases
in the patient selection process. Most studies, including
this one, often omit reporting outcomes in specific highrisk cohorts. Merely citing average patency rates may notoffer comprehensive insights into the precise mechanisms of patency failure. Factors such as stented length,
ensuring full coverage of the diseased vessel, stent inflow/
outflow adequacy, and adherence to appropriate anticoagulation protocols are crucial considerations. Multivariate analysis in previous studies has underscored stent
length as a significant predictor of late severe in-stentarea reduction [29]. There are also viewpoints suggesting that stent patency from healthy vein to healthy vein
is more important. Apprehensions about stent durability stem from instances of non-braided stents extending into the CFV. This is akin to arterial stents crossing
joints that are susceptible to neointimal hyperplasia andstent fracture, posing a potential risk of premature stent
failure [30]. The single-arm study design poses limitations on analyzing longitudinal measures like pain and
VCSS, potentially leading to an overestimation of deviceattributed improvements. It is noteworthy that the determination of stent dimensions in this study was guided
by biplanar venography rather than intravascular ultrasound, which is a limitation in the study design [31]. It
is also noteworthy that approximately 13.45% of patients
experienced total occlusion of the entire iliofemoral segments, with variations in occlusion rates between the NT
and extensively lesioned cases. These demographic characteristics suggest potential differences and challenges
compared to other studies [15, 16].

Conclusions
In conclusion, this study firmly establishes the safety andeffectiveness of an innovative iliac vein stent for managing symptomatic iliofemoral venous obstruction. The
findings can be applied to a broader real-world population grappling with chronic venous insufficiency, given
the study’s inclusion of a diverse and challenging patient
sample across 15 sites, with standardized data collectionSheng et al. BMC Medicine(2024) 22:324

Page 10 of 11

and review procedures adhering to a shared protocol.
Despite the promising 1-year outcomes observed invenous stenting, a deeper understanding necessitates further investigation into long-term results. Ongoing datacollection and analysis on this patient cohort will extend
for a period of 5 years, offering a comprehensive view ofthe stent’s enduring effectiveness and safety profile.

writing—review and editing. Y.-G.K.: investigation, writing—review andediting. B.Y.: investigation, writing—review and editing. K.Y.: investigation, writing—review and editing. P.Y.: methodology, supervision, writing—review andediting. W.W.: methodology, supervision, writing—review and editing. Trial
investigators: investigation, project administration, data curation. All authors
read and approved the final manuscript.

Research registration unique identifying number (UIN)

Availability of data and materials
No datasets were generated or analysed during the current study.

1. Name of the registry: China Clinical Trial Registration
Center.
2. Unique identifying number or registration ID:
ChiCTR2300073019.
3. Hyperlink to your specific registration (must be publicly accessible and will be checked): Home—https://​www.​ chictr.​ o rg.​ c n/ ​ hvsho ​ w proj ​ e ctEN. ​ html? ​ i d= ​ 2 3009​
2&v=​1.0.
AbbreviationsAE	adverse event(s)BMI	body mass index
CEAP	Clinical-Etiologic-Anatomic-Physiologic
CIV	common iliac vein
CFV	common femoral vein
CIVIQ-14	Chronic venous insufficiency questionnaire-14
CEC	Clinical events committee
VCSS	Venous clinical severity score
DVT	Deep vein thrombosis
DM	Diabetes mellitus
DUS	Doppler ultrasound
EIV	External iliac vein
FAS	Full analysis set
MAE	Major adverse events(s)NIVL	Non-thrombotic iliac vein lesionNT	Non-thrombotic
PPS	Per protocol set
PE	Pulmonary embolism
PT	Post-thrombotic
QOL	Quality of life
SS	Safe analysis set
WOCF	Worst-case imputation method

Supplementary Information
The online version contains supplementary material available at https://​doi.​
org/​10.​1186/​s12916-​024-​03545-2.
Additional file 1: Table S1. Inclusion and Exclusion Criteria in The Study.
Table S2. Comparison of venous stent properties. Table S3. Definitions of
Key Study Outcomes. Table S4. List of Enrolling Centers and Investigatorsin The Study. Fig. S1. Study Implementation Flowchart.
Acknowledgements
The authors would like to thank all the staff and patients in this study.
Authors’contributions
C.S.: writing—original draft, methodology, visualization, formal analysis.
X.-W.L.: investigation, writing—review and editing. H.-T.S.: investigation,
writing—review and editing. L.Z.: investigation, writing—review and editing. S.-Y.W.: investigation, writing—review and editing. H.-P.L.: investigation,
writing—review and editing. K.L.: investigation, writing—review and editing.
S.S.: investigation, writing—review and editing. Z.-J.L.: investigation, writing—review and editing. Y.-Y.L.: investigation, writing—review and editing.
G.-D.C.: investigation, writing—review and editing. M.-R.L.: investigation,

Funding
The clinical study was sponsored by Shanghai EndoVas Medical Technology
Co., Ltd.

Declarations
Ethics approval and consent to participate
Ethical approval has been obtained for this research study (GCP No.
202009217). This information has already been described in the manuscript.
Consent for publication
Not applicable.
Competing interests
The authors declare no competing interests.
Author details
1
Department of Vascular Surgery, Xiangya Hospital, Central South University,
Changsha, Hunan, China. 2 Department of Vascular Surgery, Shanghai Ninth
People’s Hospital, Shanghai JiaoTong University, Shanghai, China. 3 Departmentof Vascular Surgery, The First Affiliated Hospital of Henan University of Scienceand Technology, Luoyang, Henan, China. 4 Department of Vascular Surgery, The
First Hospital of Hebei Medical University, Shijiazhuang, Hebei, China. 5 Department of Vascular Surgery, The Second Affiliated Hospital of Anhui Medical
University, Hefei, Anhui, China. 6 Department of Vascular Surgery, Zhengzhou
People’s Hospital, Zhengzhou, Henan, China. 7 Department of Vascular Surgery,
Changsha First Hospital, Changsha, Hunan, China. 8 Department of Vascular
Surgery, The Affiliated Hospital of Southwest Medical University, Luzhou,
Sichuan, China. 9 Department of Vascular Surgery, The Second AffiliatedHospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang,
China. 10 Department of Vascular Surgery, Shijiazhuang People’s Hospital,
Shijiazhuang, Hebei, China. 11 Department of Interventional Radiology, Guangzhou First People’s Hospital, Guangzhou, Guangdong, China. 12 Departmentof Vascular Surgery, Liaocheng Second People’s Hospital, Liaocheng, Shandong, China. 13 Department of Radiology, Xiangtan Central Hospital, Xiangtan,
Hunan, China. 14 The Department of Vascular and Hernial Surgery, Ganzhou
People’s Hospital, Ganzhou, Jiangxi, China. 15 Department of Vascular Surgery,
Xiangya Third Hospital, Central South University, Changsha, Hunan, China.
16
National Clinical Research Center for Geriatric Disorders, Xiangya Hospital,
Central South University, Changsha, Hunan, China. 17 Clinical Research Center
for Vascular Intervention in Hunan Province, Xiangya Hospital, Central South
University, Changsha, Hunan, China.
Received: 27 April 2024 Accepted: 29 July 2024

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