Clinical trial NCT01872208: Evaluation of the Safety and Efficacy of a Vascular Prosthesis as an Above-Knee Bypass Graft in Patients With PAD
Official title: A Pilot Study for Evaluation of the Safety and Efficacy of Humacyte's Human Acellular Vascular Graft as an Above-Knee Femoro-Popliteal Bypass Graft in Patients With Peripheral Arterial Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Peripheral Arterial Disease
Peripheral Vascular Disease
Keywords: PAD
Atherosclerosis
Peripheral circulation
Blood Vessel Prosthesis
Tissue-Engineered Vascular Graft
Vascular Prosthesis Implantation
Femoro-Popliteal Bypass
Lead sponsor: Humacyte, Inc.
Sponsor class: INDUSTRY
Collaborators: name: FGK Clinical Research GmbH
First posted: 2013-06-07
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess the safety and efficacy of a novel, tissue-engineered vascular prosthesis, the Human Acellular Vessel (HAV).

The HAV is intended as an alternative to synthetic materials and to autologous grafts in the creation of an above-knee femoro-popliteal bypass graft in patients with peripheral arterial disease.

Detailed description: The HAV is a sterile, non-pyrogenic, acellular tubular graft composed of human collagens and other natural extra-cellular matrix proteins. Upon implantation, it is anticipated (based on pre-clinical studies) that the collagen-based matrix comprising the graft will be infiltrated with host cells and re-modeled by the host. This will result in a vascular structure more similar to the histological composition of the native vascular tissue that may improve graft longevity and be less likely to become infected.

Eligibility criteria: Inclusion Criteria:

* Patients with symptomatic peripheral arterial disease who require above knee femoro-popliteal bypass surgery
* Claudication distance of 200 m or less or rest pain or critical limb ischemia
* Preoperative angiography or angio-CT shows superficial femoral artery occlusion of \>10 cm AND graft length required ≤ 30 cm. This imaging may have been conducted up to 3 months prior to study entry provided that the patient's symptoms have remained stable since that time
* Preoperative imaging shows at least two below knee vessels patent to the ankle with good runoff
* Femoral artery occlusion is not considered suitable for endovascular treatment
* Autologous vein grafts are not suitable or feasible e.g. because of severe venous disease or prior use of leg veins for other bypass surgery or there is a clinical need to preserve those veins for future bypass surgery in the coronary or peripheral circulation
* Aged 18 to 80 years old, inclusive
* Hemoglobin ≥ 10 g/dL and platelet count ≥ 100,000/mm3 prior to Day 1
* Other hematological and biochemical parameters within a range considered acceptable for the administration of general anesthesia prior to Day 1
* Adequate liver function, defined as serum bilirubin ≤ 1.5 mg/dL; GGT, AST, ALT, and alkaline phosphatase ≤ 2x upper limit of normal or INR ≤ 1.5 prior to Day 1.
* Able to communicate meaningfully with investigative staff, competent to give written informed consent, and able to comply with entire study procedures
* Able and willing to give informed consent
* Life expectancy of at least 2 years

Exclusion Criteria:

* History or evidence of severe cardiac disease (NYHA Functional Class III or IV), myocardial infarction within six months prior to study entry (Day 1), ventricular tachyarrhythmias requiring continuing treatment, or unstable angina
* Acute injury or active infection (including positive cultures of pathogenic bacteria) in the limb receiving the graft
* Stroke within six (6) months prior to study entry (Day 1)
* Treatment with any investigational drug or device within 60 days prior to study entry (Day 1)
* Women of child bearing potential
* Active diagnosis of cancer within the previous year
* Immunodeficiency including AIDS / HIV
* Documented hypercoagulable state or history of 2 or more DVTs or other spontaneous intravascular thrombotic events
* Bleeding diathesis
* Ongoing treatment with vitamin K antagonists or direct thrombin inhibitors or factor Xa inhibitors (e.g. dabigatran, apixaban or rivaroxaban)
* Previous arterial bypass surgery (autologous vein or synthetic graft) in the operative limb
* Previous angioplasty with stenting in the operative limb unless the graft anastomoses can be made at least 1cm distant from the site of the stent
* Stenosis of \>50% of the external iliac artery unless it is planned to treat this stenosis with angioplasty with or without stenting prior to, or at the time of, graft implantation
* Distal graft anastomosis likely to be below the knee
* Active autoimmune disease - symptomatic or requiring ongoing drug therapy
* Active local or systemic infection (WBC \> 15,000/mm3)
* Known serious allergy to aspirin or penicillin
* Any other condition which in the judgment of the investigator would preclude adequate evaluation of the safety and efficacy of the HAVG
* Previous enrollment in this study
* Employees of the sponsor or patients who are employees or relatives of the investigator

Primary outcomes:
measure: Change in HAV characteristics
timeFrame: From day 5 to month 24 after HAV implantation.
measure: Change in HAV patency rate
timeFrame: From day 5 to month 24 after HAV implantation.
measure: Change in frequency and severity of Adverse Events
timeFrame: From day 1 to month 24 after HAV implantation.
measure: Change in hematology, coagulation and clinical chemistry parameters
timeFrame: From baseline to week 26 after HAV implantation.
Secondary outcomes:
measure: Change from baseline in Panel Reactive Antibody (PRA)
timeFrame: From baseline to week 26 after HAV implantation.
measure: Development of IgG antibodies
timeFrame: From baseline to week 26 after HAV implantation.
measure: HAV patency rates
timeFrame: At months 6, 12, 18 after HAV implantation.
measure: Graft interventions
timeFrame: At days 5, 15, weeks 6, 12, 16, months 12, 18, 24 after HAV implantation.
measure: Effect of graft implantation on PAD symptoms
timeFrame: From baseline to weeks 6, 12, 26, months 12, 18, 24 after HAV implantation.
measure: Effect of graft on ankle-brachial index (ABI)
timeFrame: From baseline to weeks 6, 12, 26, months 12, 18, 24 after HAV implantation.
Other outcomes:
Locations:
city: Lublin
country: Poland
facility: Clinic of Vascular Surgery and Angiology; Medical University in Lublin
city: Szczecin
country: Poland
facility: Pomeranian University in Szczecin; Clinic of General, Vascular Surgery and Angiology
city: Wrocław
country: Poland
facility: Regional Specialist Hospital in Wroclaw; Clinic of Vascular Surgery
Study officials:
affiliation: Humacyte, Inc.
name: Shamik Parikh, MD
role: STUDY_DIRECTOR
References:
citation: Gutowski P, Gage SM, Guziewicz M, Ilzecki M, Kazimierczak A, Kirkton RD, Niklason LE, Pilgrim A, Prichard HL, Przywara S, Samad R, Tente B, Turek J, Witkiewicz W, Zapotoczny N, Zubilewicz T, Lawson JH. Arterial reconstruction with human bioengineered acellular blood vessels in patients with peripheral arterial disease. J Vasc Surg. 2020 Oct;72(4):1247-1258. doi: 10.1016/j.jvs.2019.11.056. Epub 2020 Feb 21.