Trauma, Vascular System Injury
Conditions
Brief summary
This study evaluates the use of the Acellular Tissue Engineered Vessel (ATEV) in adults with vascular trauma below the neck who are undergoing vascular reconstructive surgery. There will be an extremity cohort and an torso cohort. All subjects will be implanted with an ATEV as an interposition vessel or bypass using standard vascular surgical techniques. There is no control arm.
Detailed description
This is a prospective, multicenter, multi cohort, non-randomized phase 2/3 study in adult patients with life or limb threatening vascular trauma which requires surgical repair. There will be an extremity cohort and a torso cohort. The extremity cohort will include patients who require repair of a vessel contained to the upper or lower extremity. The torso cohort includes patients who require repair of vessels within the thorax (excluding the heart), abdomen, and retroperitoneum. Subjects will be implanted with an ATEV as an interposition vessel or bypass using standard vascular surgical techniques. There is no control arm. The active study duration for each study participant will be 36 months from implantation or until ATEV failure/ removal/ death, if earlier. Follow up after month 12 will involve the capture of information on assessments performed at "standard of care" routine clinic visits or by telephone follow up with the patient or his/her physician with physical exam and ultrasound at month 24 and month 36.
Interventions
The investigational medicinal product (IMP) - the Acellular Tissue Engineered Vessel (ATEV) is a sterile acellular tubular graft composed of human collagen types I and III and other extracellular matrix proteins, including fibronectin and vitronectin which can be used for arterial bypass or reconstruction in patients with life or limb threatening vascular trauma. The vessel is 6 mm in diameter and approximately 42 cm in length. The product is supplied on a silicone mandrel immersed in sterile phosphate buffered saline in a sealed and labeled plastic container. The ATEV is implanted using standard vascular surgical techniques similar to placement of predicate peripheral vascular prostheses.
Sponsors
Humacyte, Inc.
Atlantic Research Group
U.S. Army Medical Research and Development Command
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Patients with life or limb threatening traumatic injury to an arterial vessel in the limb or torso, other than the heart, which requires replacement or reconstruction * Preoperative imaging or clinical examination indicates the damaged vessel has a defect length of ≤ 38cm and is appropriately size matched to the 6 mm Acellular Tissue Engineered Vessel (ATEV) per the judgment of the treating surgeon taking into account vasoconstriction and situational inflow and outflow considerations. * Autologous vein graft is either not feasible in the judgment of the treating surgeon (e.g. because of lack of availability of suitable conduit, presence of severe venous insufficiency) or is not desirable because of the urgency of revascularization * Able to communicate meaningfully with investigative staff, and able to comply with entire study procedures. If the patient is unconscious, then information from a reliable witness indicates that the patient would normally be able to comply with study procedures * Patient or relative is able, willing and competent to give informed consent * Life expectancy of at least 1 year
Exclusion criteria
* Mangled Extremity Severity Score (MESS) of ≥ 7 * Limb at high risk of amputation despite vascular reconstruction (e.g., because of crush injury) * Catastrophic injuries that make survival unlikely (e.g. Abbreviated Injury Scale (AIS) \> 5 or Injury Severity Score (ISS) \>60) * ATEV may not be used for coronary artery repair * Known pregnant women * Known medical condition which would preclude long term antiplatelet therapy after resolution of acute injuries * Any other condition which in the judgment of the investigator would preclude adequate evaluation of the safety and efficacy of the ATEV * Previous exposure to ATEV * Known participation in any investigational study within the last 30 days * Employees of the sponsor or patients who are employees or relatives of the investigator
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary Patency Rate of the Human Acellular Vessel (HAV) at Day 30 in the All HAV Group | 30 days from time of implantation | Rate of primary patency at the specified milestone post-implantation, evaluated across the entire overall study population who received the Human Acellular Vessel (HAV). Primary patency is defined as the continuous presence of blood flow through the HAV conduit from the time of surgical placement until the evaluation milestone, without requiring any intervening surgical or endovascular interventions to maintain or re-establish flow. |
| Primary Patency Rate of the Human Acellular Vessel (HAV) at Day 30 in the Extremity Community-Acquired Trauma Subgroup | 30 days from time implantation | Rate of primary patency at 30 days post-implantation, evaluated strictly within the sub-cohort of participants presenting with non-iatrogenic, community-acquired extremity vascular trauma. Primary patency is defined as the continuous presence of blood flow through the HAV conduit from the time of surgical placement until the 30-day evaluation milestone, without requiring any intervening surgical or endovascular interventions to maintain or re-establish flow. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Secondary Patency Rate of the Human Acellular Vessel (HAV) at Day 30 in the All HAV Group | 30 days from time of implantation | Rate of secondary patency at the specified milestone post-implantation, evaluated across the entire overall study population who received the Human Acellular Vessel (HAV). Secondary patency is defined as the continuous presence of blood flow through the HAV conduit from the time of surgical placement until the evaluation milestone, including vessels that became occluded but were successfully restored to patency via intervening endovascular or surgical re-intervention (e.g., thrombectomy, thrombolysis, or patch angioplasty). |
| HAV Infection Free Rate at Day 30 in the All HAV Group | 30 days from time of implantation | The percentage of participants who remained entirely free from a confirmed, adjudicated infection of the implanted Human Acellular Vessel (HAV) conduit through the specified follow-up milestone, evaluated across the entire overall study population. An infection event is defined by clinical signs coupled with microbiologic confirmation from wound/perigraft cultures, or an independent clinical adjudication confirming a graft-specific infectious complication requiring targeted antibiotic therapy, surgical debridement, or explantation. |
| Limb Salvage Rate at Day 30 in the All HAV Group | 30 Days from time of implantation | Rate of successful limb salvage at the specified milestone post-implantation, evaluated across the entire overall study population who received the Human Acellular Vessel (HAV). Limb salvage is defined as the preservation of the treated upper or lower extremity without the requirement for a major secondary amputation (defined as an amputation performed at or proximal to the wrist or ankle joints) during the follow-up window. |
| Survival Rate at Day 30 in the All HAV Group | 30 Days from time of implantation | Survival at the specified milestone post-implantation, evaluated across the entire overall study population who received the Human Acellular Vessel (HAV). Under While-on-Treatment analysis all cases without any evidence of death are imputed as having survived. |
| Kaplan-Meier Estimates of Long-term Primary Patency in the All HAV Group | 12 months from time of implantation | Time-to-event analysis estimating the long-term cumulative probabilities of maintaining HAV primary patency through the 12-month follow-up period, evaluated across the entire overall study population. This metric reports the explicit Kaplan-Meier survival probability estimates and accompanying 95% Confidence Intervals calculated at the Month 12 milestones. Standard censoring rules apply to participants who died, withdrew early, or reached the data cutoff milestone without an event. |
| Kaplan-Meier Estimates of Long-term Secondary Patency in the All HAV Group | 12 months from time of implantation | Time-to-event analysis estimating the long-term cumulative probabilities of maintaining HAV secondary patency through the 12-month follow-up period, evaluated across the entire overall study population. This metric reports the explicit Kaplan-Meier survival probability estimates and accompanying 95% Confidence Intervals calculated at the Month 12 milestones. Standard censoring rules apply to participants who died, withdrew early, or reached the data cutoff milestone without an event. |
| Kaplan-Meier Estimate of Long-term Infection-free HAV Rates in the All HAV Group | 12 months from time of implantation | Time-to-event analysis estimating the long-term cumulative probabilities of Infection-fee HAV rates through the 12-month follow-up period, evaluated across the entire overall study population. This metric reports the explicit Kaplan-Meier survival probability estimates and accompanying 95% Confidence Intervals calculated at the Month 12 milestones. Standard censoring rules apply to participants who died, withdrew early, or reached the data cutoff milestone without an event. |
| Kaplan-Meier Estimate of Long-term Limb Salvage Rates in the All HAV Group | 12 months from time of implantation | Time-to-event analysis estimating the long-term cumulative probabilities of limb salvage through the 12-month follow-up period, evaluated across the entire overall study population. This metric reports the explicit Kaplan-Meier survival probability estimates and accompanying 95% Confidence Intervals calculated at the Month 12 milestones. Standard censoring rules apply to participants who died, withdrew early, or reached the data cutoff milestone without an event. |
| Kaplan-Meier Estimate of Long-term Patient Survival in the All HAV Group | 12 months from implantation | Time-to-event analysis estimating the long-term cumulative probabilities of patient survival through the 12-month follow-up period, evaluated across the entire overall study population. This metric reports the explicit Kaplan-Meier survival probability estimates and accompanying 95% Confidence Intervals calculated at the Month 12 milestones. Standard censoring rules apply to participants who died, withdrew early, or reached the data cutoff milestone without an event. |
| Kaplan-Meier Estimate of Long-term Primary Patency Rates in the All HAV Group | 36 months from time of implantation | Time-to-event analysis estimating the long-term cumulative probabilities of maintaining HAV primary patency through the 36-month follow-up period, evaluated across the entire overall study population. This metric reports the explicit Kaplan-Meier survival probability estimates and accompanying 95% Confidence Intervals calculated at the Month 36 milestones. Standard censoring rules apply to participants who died, withdrew early, or reached the data cutoff milestone without an event. |
| Kaplan-Meier Estimate of Long-term Secondary Patency Rates in the All HAV Group | 36 months from time of implantation | Time-to-event analysis estimating the long-term cumulative probabilities of maintaining HAV secondary patency through the 36-month follow-up period, evaluated across the entire overall study population. This metric reports the explicit Kaplan-Meier survival probability estimates and accompanying 95% Confidence Intervals calculated at the Month 36 milestones. Standard censoring rules apply to participants who died, withdrew early, or reached the data cutoff milestone without an event. |
| HAV Interventions Required to Maintain/Restore Patency in the All HAV Group | 30 days from time of implantation | Number of participants with at least 1 intervention required to maintain/restore patency of the HAV. |
| Secondary Patency Rate of the Human Acellular Vessel (HAV) at Day 30 in the Extremity Community-Acquired Trauma Subgroup | 30 days from time of implantation | Rate of secondary patency at 30 days post-implantation, evaluated within the sub-cohort of participants presenting with non-iatrogenic, community-acquired extremity vascular trauma. Secondary patency is defined as the continuous presence of blood flow through the HAV conduit from the time of surgical placement until the 30-day evaluation milestone, including vessels that became occluded but were successfully restored to patency via intervening endovascular or surgical re-intervention (e.g., thrombectomy, thrombolysis, or patch angioplasty). |
| HAV Infection-free Rates at Day 30 in the Extremity Community-Acquired Trauma Subgroup | 30 days from time of implantation | The percentage of participants who remained entirely free from a confirmed, adjudicated infection of the implanted Human Acellular Vessel (HAV) conduit through the follow-up period. An infection event is defined by clinical signs (e.g., localized purulence, exposed graft, erythema) coupled with microbiologic confirmation from wound/perigraft cultures, or an independent clinical adjudication confirming a graft-specific infectious complication requiring targeted antibiotic therapy, surgical debridement, or explantation. Participants who did not experience an adjudicated graft infection are considered infection-free. |
| Limb Salvage Rate at Day 30 in the Extremity Community-Acquired Trauma Subgroup | 30 Days from time of implantation | Rate of successful limb salvage at 30 days post-implantation, evaluated within the sub-cohort of participants presenting with non-iatrogenic, community-acquired extremity vascular trauma. Limb salvage is defined as the preservation of the treated upper or lower extremity without the requirement for a major secondary amputation (defined as an amputation performed at or proximal to the wrist or ankle joints) during the 30-day follow-up window. |
| Survival Rate at Day 30 in the Extremity Community-Acquired Trauma Subgroup | 30 Days from time of implantation | Survival at 30 days post-implantation, evaluated within the sub-cohort of participants presenting with non-iatrogenic, community-acquired extremity vascular trauma. Under While-on-Treatment analysis all cases without any evidence of death are imputed as having survived. |
| Kaplan-Meier Estimates of Long-term Primary Patency in the Extremity Community-Acquired Trauma Subgroup | 12 months from time of implantation | Time-to-event analysis estimating the long-term cumulative probabilities of maintaining HAV primary patency through the 12-month follow-up period, evaluated across the pre-specified subgroup of participants enrolled with community-acquired vascular trauma restricted to the upper or lower extremities (n=54). To ensure precise efficacy evaluation within this clinical cohort, this specific analysis population excludes all study participants who presented with torso arterial trauma, as well as those treated for iatrogenic, hospital-acquired vascular injuries. This metric reports the explicit Kaplan-Meier survival probability estimates and accompanying 95% Confidence Intervals calculated at the Month 12 milestones. Standard censoring rules apply to participants who died, withdrew early, or reached the data cutoff milestone without an event. |
| Kaplan-Meier Estimate of Long-term Secondary Patency Rates in the Extremity Community Acquired Injury Trauma Subgroup | 12 months from time of implantation | Time-to-event analysis estimating the long-term cumulative probabilities of maintaining HAV secondary patency through the 12-month follow-up period, evaluated across the Extremity Community Acquired Injury Trauma Subgroup. This metric reports the explicit Kaplan-Meier survival probability estimates and accompanying 95% Confidence Intervals calculated at the Month 12 milestones. Standard censoring rules apply to participants who died, withdrew early, or reached the data cutoff milestone without an event. |
| Kaplan-Meier Estimates of Infection-free HAV Rates in the Extremity Community-Acquired Trauma Subgroup | 12 months from time of implantation | Time-to-event analysis estimating the long-term cumulative probabilities of Infection-free HAV rates through the 12-month follow-up period, evaluated across the pre-specified subgroup of participants enrolled with community-acquired vascular trauma restricted to the upper or lower extremities (n=54). To ensure precise efficacy evaluation within this clinical cohort, this specific analysis population excludes all study participants who presented with torso arterial trauma, as well as those treated for iatrogenic, hospital-acquired vascular injuries.. This metric reports the explicit Kaplan-Meier survival probability estimates and accompanying 95% Confidence Intervals calculated at the Month 12 milestones. Standard censoring rules apply to participants who died, withdrew early, or reached the data cutoff milestone without an event. |
| Kaplan-Meier Estimates of Limb Salvage Rates in the Extremity Community-Acquired Trauma Subgroup | 12 months from time of implantation | Time-to-event analysis estimating the long-term cumulative probabilities of limb salvage rates through the 12-month follow-up period, evaluated across the pre-specified subgroup of participants enrolled with community-acquired vascular trauma restricted to the upper or lower extremities (n=54). To ensure precise efficacy evaluation within this clinical cohort, this specific analysis population excludes all study participants who presented with torso arterial trauma, as well as those treated for iatrogenic, hospital-acquired vascular injuries.. This metric reports the explicit Kaplan-Meier survival probability estimates and accompanying 95% Confidence Intervals calculated at the Month 12 milestones. Standard censoring rules apply to participants who died, withdrew early, or reached the data cutoff milestone without an event. |
| Kaplan-Meier Estimates of Patient Survival in the Extremity Community-Acquired Trauma Subgroup | 12 months from time of implantation | Time-to-event analysis estimating the long-term cumulative probabilities of patient survival through the 12-month follow-up period, evaluated across the pre-specified subgroup of participants enrolled with community-acquired vascular trauma restricted to the upper or lower extremities (n=54). To ensure precise efficacy evaluation within this clinical cohort, this specific analysis population excludes all study participants who presented with torso arterial trauma, as well as those treated for iatrogenic, hospital-acquired vascular injuries.. This metric reports the explicit Kaplan-Meier survival probability estimates and accompanying 95% Confidence Intervals calculated at the Month 12 milestones. Standard censoring rules apply to participants who died, withdrew early, or reached the data cutoff milestone without an event. |
| HAV Interventions Required to Maintain/Restore Patency in the Extremity Community Acquired Injury Trauma Subgroup | 30 days from time of implantation | Number of participants with at least 1 intervention required to maintain/restore patency of the HAV. |
Countries
Israel, United States
Contacts
STUDY_DIRECTORShamik Parikh, MD
Humacyte, Inc.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 36.9 Age (years) |
| Injury Etiology Hospital acquired injury | 12 Participants |
| Injury Etiology Industrial accident | 3 Participants |
| Injury Etiology Injury (gunshot) | 34 Participants |
| Injury Etiology Motor vehicle accident | 14 Participants |
| Injury Etiology Other | 9 Participants |
| Injury Severity - Abbreviated Injury Scale Critical | 20 Participants |
| Injury Severity - Abbreviated Injury Scale Moderate | 2 Participants |
| Injury Severity - Abbreviated Injury Scale Not available | 4 Participants |
| Injury Severity - Abbreviated Injury Scale Serious | 16 Participants |
| Injury Severity - Abbreviated Injury Scale Severe | 30 Participants |
| Location of Vascular Injury Lower Extremity | 51 participants |
| Location of Vascular Injury Torso/Chest/Abdomen | 6 participants |
| Location of Vascular Injury Upper Extremity | 15 participants |
| Nature of Trauma Blunt | 24 Participants |
| Nature of Trauma Penetrating | 48 Participants |
| Race/Ethnicity, Customized Black or African American | 35 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 1 Participants |
| Race/Ethnicity, Customized Other | 5 Participants |
| Race/Ethnicity, Customized White | 31 Participants |
| Region of Enrollment Israel | 4 Participants |
| Region of Enrollment United States | 68 Participants |
| Sex: Female, Male Female | 20 Participants |
| Sex: Female, Male Male | 52 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 12 / 72 |
| other Total, other adverse events | 70 / 72 |
| serious Total, serious adverse events | 48 / 72 |
Outcome results
None listed