Chronic Venous Insufficiency (CVI), Deep Vein Reflux
Conditions
Brief summary
Prospective, non-randomized, multicenter pre-market early feasibility study (EFS) to evaluate subjects treated with the BlueLeaf System for the treatment of symptomatic chronic venous insufficiency (CVI) of the lower extremity
Detailed description
The purpose of this early feasibility study is to provide information on the BlueLeaf System for the formation of one or more autogenous vein valves constructed from the vein wall of the femoral and/or popliteal vein, in subjects with CVI and who meet the specified eligibility criteria. In particular, the safety and technical feasibility of the procedure will be validated in patients in the United States, including the procedural steps, operator technique, and subject characteristics. The study will assess the safety and effectiveness of the study device acutely and through 5 years.
Interventions
DEVICEBlueLeaf® Endovenous Valve Formation System (BlueLeaf System)
The BlueLeaf System is a single-use, disposable device designed to modify the vein wall to form one or more functional autogenous valves to improve the hemodynamics of the deep venous system treated.
Sponsors
Intervene, Inc.
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
Key Inclusion Criteria * Failed at least 6 months of conservative therapy at some point during the course of their CVI management (symptoms not adequately resolved or patient non-compliant/unable to tolerate) * Deep system venous reflux characterized by \>1 second reflux time in two vein segments (vein segments defined as: proximal femoral, distal femoral, and popliteal), as assessed by duplex ultrasound (DUS) with patient in the standing position * Presence of at least two potential target sites within a target vessel as assessed preliminarily by DUS, with a target site being defined as a segment within the femoral or popliteal vein that is: 7mm to 11mm in luminal diameter and at least 3cm long and absent features that, in the Investigator's opinion, would preclude formation of a monocuspid valve (at any orientation). * In the Investigator's opinion, the subject is a good candidate for treatment with the BlueLeaf System based on their symptoms, quality of life, anatomy, and the likelihood of benefit from continued conservative therapy Key
Exclusion criteria
* Untreated significant superficial venous incompetence which, in the opinion of the Investigator, may be the primary source of existing symptoms * Acute deep venous thrombosis (DVT) within 1 year of consent * Deep venous intervention (includes stenting) in the target limb or outflow vessels within 3 months of consent * Flow-limiting venous outflow obstruction central to the intended target sites, defined by a common femoral vein duplex exam found to have a continuous waveform without respiratory variation * Contraindications to all protocol specified anticoagulation options * Known and uncontrolled hypercoagulopathy (i.e. hypercoagulopathy that cannot be adequately managed/controlled with medication) * Women on long-term oral contraceptives * Non-ambulatory patients * Significant peripheral arterial disease with an ankle-brachial index of \< 0.70 or with incompressible vessels * New York Heart Association Class III or IV heart failure * Patients with a history of right heart failure occurring as a consequence of, for example, biventricular failure, intrinsic pulmonary disease, chronic thromboembolic pulmonary hypertension, and other etiologies that result in elevated right-sided pressures. * Active systemic infection * Invasive surgical procedure within the last 3 months that in the Investigator's opinion would interfere with the study procedure or results * Chronic renal insufficiency with creatinine level of ≥ 2mg/dL * Hemoglobin level \< 9.0 mg/dL * Platelet count \< 50,000 or \> 1,000,000/mm3 * Total white blood cell count \< 3,000/mm3 * Subject is enrolled in another clinical study that, in the opinion of the Investigator, may conflict with this study or compromise study results * Comorbidity risks or other concerns which, in the opinion of the Investigator, either limits longevity or likelihood of complying with the protocol and its prescribed follow up (e.g. recent cancer or stroke); or precludes patient from being transitioned to open surgery if complication requiring surgical intervention occurs during the procedure (such as severe vein laceration).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary Safety Endpoint: The Number of Subjects Experiencing a Major Adverse Event (MAE), Composed of the Following | 30-day post-procedure | * Symptomatic pulmonary embolism * DVT anywhere in the deep venous system of the treatment limb * Occlusive valve pocket thrombus (VPT) * Non-occlusive stenosis in the target vessel (including due to scarring, inflammation, VPT, etc.) leading to persistent worsening of symptoms attributable to venous flow obstruction, or requiring post-procedural surgical or endovascular re-intervention * Device or procedure-related venous or arterial injury in the treated limb (such as Arteriovenous Fistula (AVF's), bleeding, pseudo aneurysm) leading to worsening of symptoms that require post-procedural surgical or endovascular re-intervention or requiring transfusion of more than 2 units of blood. (Note: Peri-procedural stiches placed to assist with closure of the access site will not be characterized as a primary safety failure.) * Device or procedure-related death |
| Change in Revised Venous Clinical Severity Score (rVCSS) From Baseline | Baseline, 30-days, 12-weeks, 210-days and 365-days post-procedure | Assessment of changes in the rVCSS; the score is a composite based on a rating score of none (0), mild (1), moderate (2) and severe (3) for symptoms and clinical signs, the number of active ulcers (0, 1, 2, \>/=3), duration of ulcers (\<3 months, \>3 months but \<1 year, not healed for \>1 year), active ulcer size (diameter \<2cm, diameter 2-6cm, and diameter \>6cm), and use of compression therapy (not used (0), intermittent use of stockings (1), wears stockings most days (2), and full compliance (3)). A higher VCSS would indicate a worse outcome. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Investigational Subjects will be treated with the investigational device and followed per protocol.
BlueLeaf® Endovenous Valve Formation System (BlueLeaf System): The BlueLeaf System is a single-use, disposable device designed to modify the vein wall to form one or more functional autogenous valves to improve the hemodynamics of the deep venous system treated. | 15 |
| Total | 15 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Trial termination | 15 |
Baseline characteristics
| Characteristic | Investigational |
|---|---|
| Age, Continuous | 60.7 years STANDARD_DEVIATION 10.2 |
| Chronic Kidney Disease No | 13 Participants |
| Chronic Kidney Disease Yes | 2 Participants |
| Clinical-Etiology-Anatomy-Pathophysiology (CEAP) Classification C3 - edema | 0 Participants |
| Clinical-Etiology-Anatomy-Pathophysiology (CEAP) Classification C4 - changes in skin and subcutaneous tissue secondary to chronic venous disease | 0 Participants |
| Clinical-Etiology-Anatomy-Pathophysiology (CEAP) Classification C5 - healed | 7 Participants |
| Clinical-Etiology-Anatomy-Pathophysiology (CEAP) Classification C6 - active venous ulcer | 3 Participants |
| Clinical-Etiology-Anatomy-Pathophysiology (CEAP) Classification C6r - recurrent active venous ulcer | 5 Participants |
| Deep Venous Thrombosis (DVT) Bilateral | 1 Participants |
| Deep Venous Thrombosis (DVT) Left | 3 Participants |
| Deep Venous Thrombosis (DVT) None | 6 Participants |
| Deep Venous Thrombosis (DVT) Right | 5 Participants |
| Diabetes None | 12 Participants |
| Diabetes Type 1 | 0 Participants |
| Diabetes Type 2 | 3 Participants |
| History of Chronic Obstructive Pulmonary Disease (COPD) No | 14 Participants |
| History of Chronic Obstructive Pulmonary Disease (COPD) Yes | 1 Participants |
| History of Chronic Venous Insufficiency (CVI) No | 0 Participants |
| History of Chronic Venous Insufficiency (CVI) Yes | 15 Participants |
| History of Congestive Heart Failure (CHF) No | 14 Participants |
| History of Congestive Heart Failure (CHF) Yes | 1 Participants |
| History of Coronary Artery Disease No | 14 Participants |
| History of Coronary Artery Disease Yes | 1 Participants |
| History of Corona Virus Disease 2019 (COVID-19) Current | 0 Participants |
| History of Corona Virus Disease 2019 (COVID-19) None | 12 Participants |
| History of Corona Virus Disease 2019 (COVID-19) Previous | 1 Participants |
| History of Corona Virus Disease 2019 (COVID-19) Unknown | 2 Participants |
| History of Hypercoagulable Syndrome No | 13 Participants |
| History of Hypercoagulable Syndrome Yes, active | 2 Participants |
| History of Hypercoagulable Syndrome Yes, inactive | 0 Participants |
| History of Malignancy No | 14 Participants |
| History of Malignancy Yes, active | 0 Participants |
| History of Malignancy Yes, inactive | 1 Participants |
| History of Peripheral Artery Disease (PAD) No | 14 Participants |
| History of Peripheral Artery Disease (PAD) Yes, active | 1 Participants |
| History of Peripheral Artery Disease (PAD) Yes, inactive | 0 Participants |
| History of Pulmonary Embolism No | 12 Participants |
| History of Pulmonary Embolism Yes | 3 Participants |
| History of Stroke No | 15 Participants |
| History of Stroke Yes | 0 Participants |
| Prior Deep Venous System or Outflow Vessel Intervention No | 8 participants |
| Prior Deep Venous System or Outflow Vessel Intervention Yes | 7 participants |
| Prior Fem-pop Balloon Angioplasty Bilateral | 1 procedures |
| Prior Fem-pop Balloon Angioplasty Left | 0 procedures |
| Prior Fem-pop Balloon Angioplasty Right | 2 procedures |
| Prior Inferior Vena Cava (IVC) Filter Placement No | 12 Participants |
| Prior Inferior Vena Cava (IVC) Filter Placement Yes, filter not present | 1 Participants |
| Prior Inferior Vena Cava (IVC) Filter Placement Yes, filter still present | 2 Participants |
| Prior Superficial Vein Treatment Endovenous ablation/closure | 7 procedures |
| Prior Superficial Vein Treatment Foam sclerotherapy | 3 procedures |
| Prior Superficial Vein Treatment None | 7 procedures |
| Prior Superficial Vein Treatment Surgical stripping/ligation | 4 procedures |
| Prior Thrombectomy Bilateral | 0 procedures |
| Prior Thrombectomy Left | 0 procedures |
| Prior Thrombectomy Right | 0 procedures |
| Prior Venous Stenting Bilateral | 0 procedures |
| Prior Venous Stenting Left | 2 procedures |
| Prior Venous Stenting Right | 2 procedures |
| Prior Venous Valve Reconstruction Surgery Bilateral | 0 procedures |
| Prior Venous Valve Reconstruction Surgery Left | 0 procedures |
| Prior Venous Valve Reconstruction Surgery Right | 0 procedures |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 12 Participants |
| Region of Enrollment United States | 15 participants |
| Revised Venous Clinical Severity Score (rVCSS) | 14.4 score on a scale STANDARD_DEVIATION 4.2 |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 9 Participants |
| Smoker Current | 2 Participants |
| Smoker Former | 6 Participants |
| Smoker Never | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 15 |
| other Total, other adverse events | 12 / 15 |
| serious Total, serious adverse events | 4 / 15 |
Outcome results
Primary
Change in Revised Venous Clinical Severity Score (rVCSS) From Baseline
Assessment of changes in the rVCSS; the score is a composite based on a rating score of none (0), mild (1), moderate (2) and severe (3) for symptoms and clinical signs, the number of active ulcers (0, 1, 2, \>/=3), duration of ulcers (\<3 months, \>3 months but \<1 year, not healed for \>1 year), active ulcer size (diameter \<2cm, diameter 2-6cm, and diameter \>6cm), and use of compression therapy (not used (0), intermittent use of stockings (1), wears stockings most days (2), and full compliance (3)). A higher VCSS would indicate a worse outcome.
Time frame: Baseline, 30-days, 12-weeks, 210-days and 365-days post-procedure
Population: Only available data is reported and therefore, the number analyzed may differ across the timepoints
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Investigational | Change in Revised Venous Clinical Severity Score (rVCSS) From Baseline | 30-day Score | 13.5 score on a scale | Standard Deviation 5.4 |
| Investigational | Change in Revised Venous Clinical Severity Score (rVCSS) From Baseline | 365-day Score | 11.5 score on a scale | Standard Deviation 4.8 |
| Investigational | Change in Revised Venous Clinical Severity Score (rVCSS) From Baseline | Change from Baseline - 365-day | -2.3 score on a scale | Standard Deviation 4.3 |
| Investigational | Change in Revised Venous Clinical Severity Score (rVCSS) From Baseline | Baseline Score | 14.1 score on a scale | Standard Deviation 4.2 |
| Investigational | Change in Revised Venous Clinical Severity Score (rVCSS) From Baseline | Change from Baseline - 30-day | -0.4 score on a scale | Standard Deviation 5.5 |
| Investigational | Change in Revised Venous Clinical Severity Score (rVCSS) From Baseline | 12-week Score | 12.6 score on a scale | Standard Deviation 4.8 |
| Investigational | Change in Revised Venous Clinical Severity Score (rVCSS) From Baseline | Change from Baseline - 12-week | -1.4 score on a scale | Standard Deviation 5.4 |
| Investigational | Change in Revised Venous Clinical Severity Score (rVCSS) From Baseline | 210-day Score | 11.3 score on a scale | Standard Deviation 5.3 |
| Investigational | Change in Revised Venous Clinical Severity Score (rVCSS) From Baseline | Change from Baseline - 210-day | -2.4 score on a scale | Standard Deviation 4.3 |
Primary
Primary Safety Endpoint: The Number of Subjects Experiencing a Major Adverse Event (MAE), Composed of the Following
* Symptomatic pulmonary embolism * DVT anywhere in the deep venous system of the treatment limb * Occlusive valve pocket thrombus (VPT) * Non-occlusive stenosis in the target vessel (including due to scarring, inflammation, VPT, etc.) leading to persistent worsening of symptoms attributable to venous flow obstruction, or requiring post-procedural surgical or endovascular re-intervention * Device or procedure-related venous or arterial injury in the treated limb (such as Arteriovenous Fistula (AVF's), bleeding, pseudo aneurysm) leading to worsening of symptoms that require post-procedural surgical or endovascular re-intervention or requiring transfusion of more than 2 units of blood. (Note: Peri-procedural stiches placed to assist with closure of the access site will not be characterized as a primary safety failure.) * Device or procedure-related death
Time frame: 30-day post-procedure
Population: All subjects that were treated with the investigational device
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Investigational | Primary Safety Endpoint: The Number of Subjects Experiencing a Major Adverse Event (MAE), Composed of the Following | 0 Participants |