Physicians
HUMANITY Clinical Trial for AV Access
ATTENTION CLINICIAN: The purpose of this website is to alert you that this patient is enrolled in the HUMANITY Phase III Clinical Trial for AV Access.
Be advised, balloon for angioplasty or thrombectomy SHOULD NOT EXCEED 6MM in diameter within the HAV as disruption or tearing of HAV may occur.
Humacyte HUMANITY™ Phase III Clinical Trial
STUDY POPULATION:
ESRD patients who are not or are no longer candidates for fistula placement
STUDY SITES:
Approximately 35 Sites in the US, Europe, and Israel
ENROLLMENT:
At least 350 patients
RANDOMIZATION:
1:1 ePTFE : HAV
ENROLLMENT PERIOD:
Approximately 16 months
EXPECTED START DATE:
May 2016
FOLLOW UP PERIOD:
Up to 5 years
SPONSOR:
Humacyte, Inc.
CONTACT:
Medical Monitor by Region US: 1-800-723-2890 Israel: 1-809-315655 Poland: 00-800-112-4013 Portugal: 800-180-259 UK: 0-800-014-8926 Germany: 0800-183-8461
The Humanity Phase III clinical trial will compare the HAV with the current standard of care dialysis graft, ePTFE when used for hemodialysis access in the above study population. Below you will find intervention guidelines, cannulation guidelines, and more information about the Humacyte technology, including the HUMANITY clinical trial, and results from the Phase II study.
Content approved by WIRB 28 May, 2016
Intervention Guidelines
In the event of study access (SA) occlusion or poor performance, established vascular access revision procedures should be considered. Appropriate revision procedure selection should be determined by the surgical team based on the specific case requirements, and whether the SA is an AVF, AVG, or HAV. Thrombectomy of any of these SAs may be performed in an open or percutaneous fashion depending on the technical faculties available or that may be required. Primary surgical revision may be performed whenever deemed appropriate.
- Prior to study access intervention, a contrast study should be performed and documented.
- If a clinically significant stenosis based on imaging and clinical symptoms is detected, balloon angioplasty or other appropriate surgical or endovascular procedures can be performed at the same session.
- Interventions should be driven by clinical symptoms not by study mandated imaging. If clinically significant stenosis is noted, then intervention is warranted if symptomatic.
- Balloons (angioplasty or thrombectomy) should not exceed 6mm in diameter within the body of the HAV.
- Non-compliant angioplasty balloons are recommended for use within the HAV body.
- Cutting balloons should not be used within the body of the HAV, however, use at the anastomoses is permitted.
- The use of long balloons (e.g. > 6cm in length) within looped configurations of the HAV, or near tight curves may result in damage to the vessel as the “shoulders” of the balloon expand to a linear conformation.
- Vascular sheaths used for direct access into the HAV should remain as small as feasible, preferably no larger than 7F.
- For surgical revision cases, please remember to save a tissue specimen for the study sponsor, if medically appropriate.
Thrombectomy Procedures
OPEN THROMBECTOMY
- Standard open thrombectomy techniques.
- For open procedures, we recommend gaining adequate control of inflow and outflow prior to incising the SA.
- Recommend using a #11 blade knife to create a vessel or graft-otomy on the anterior half of the access.
- Maximum inflated embolectomy balloon SHOULD NOT EXCEED 6mm IN DIAMETER within the HAV.
- Any balloon that is inflated beyond 6mm within the HAV may lead to disruption or tearing of the HAV and thus, we recommend congruent balloon thrombectomy practices.
PERCUTANEOUS THROmBECTOMY
- Standard percutaneous thrombectomy techniques.
- Maintain small sheath access when possible.
- Maximum inflated embolectomy balloon should not exceed 6mm in diameter within the HAV.
Any balloon that is inflated beyond 6mm within the HAV may lead to disruption or tearing of the HAV and thus, we recommend congruent balloon thrombectomy practices.
CAUTION: Mechanical, suction, or rotational thrombectomy devices (i.e. Angiojet, Arrow-Trerotola, Amplatz, Trellis, Ekos, etc.) have not been rigorously tested for safety or efficacy within the HAV. We cannot recommend use of these devices for thrombectomy procedures within the HAV until adequate safety testing has been performed. These devices and methods ARE ACCEPTABLE to use within the comparator AVF during this clinical trial.
Angioplasty Procedures
- Standard percutaneous thrombectomy techniques are acceptable.
- Maintain small sheath access when possible.
- Recommend 5Fr vascular sheath, but no larger than 7Fr sheath access.
- Recommend the use of a non-compliant angioplasty balloon.
- Balloon should not exceed 6mm in diameter within the body of the HAV.
- If a venous anastomotic stenosis becomes refractory to treatment with a 6mm balloon, it is permissible to use a 7mm balloon to treat residual stenosis in that area only.
- Balloon length should remain as short as possible to avoid over dilating areas outside of the stenosis.
- Balloons > 6mm in diameter may be used at the anastomoses as long as the body of the balloon remains outside of the HAV.
CAUTION:
- Any balloon that is inflated beyond 6mm within the HAV may lead to disruption or tearing of the HAV.
- The use of long balloons (e.g. > 6cm in length) within looped configurations of the HAV, or near tight curves may result in damage to the vessel as the “shoulders” of the balloon expand to a linear conformation.
- Cutting balloons should not be used within the body of the HAV, however, use at the anastomoses is permitted.
- Drug coated balloons (DCBs) have not been rigorously tested for safety or efficacy within the HAV. We cannot recommend the use of DCBs within the HAV until adequate safety testing has been performed.
Venous anastomotic stenosis should be managed using a 6mm balloon initially. If the result is inadequate, serial angioplasty with a 6mm or 7mm balloon may be used on the residual stenosis. A balloon larger than 7mm should not be used since this may disrupt the HAV. If the stenosis is not adequately resolved, covered stent placement or surgical revision should be considered.
Stenting Procedures
- Use of stents in the HAV are allowed and should be consistent with standard AVF and AVG access management practices.
- Intravascular stents may be used in cases where an adequate result is not obtained by angioplasty alone.
- At the anastomoses, a covered stent is preferable to minimize the risk of in-stent restenosis.
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Placement of a stent of any type within the cannulation zone of an AVF, AVG, or HAV to treat stenosis or pseudoaneurysm should be avoided because of the increased risk of complications such as an infection.
Stent-graft placement within the SA to treat acute hemorrhage is acceptable, but eventual revision by surgical reconstruction is recommended. Following any angioplasty or stenting procedure, post-intervention images (completion) should be obtained.
CAUTION: Drug eluting stents (DESs) have not been rigorously tested for safety or efficacy within the HAV. We cannot recommend the use of DESs within the HAV until adequate safety testing has been performed.
Surgical Interventions
- Surgical interventions or revisions are permitted and should be performed at the discretion of the surgical team
- Any method is permissible
- Additional HAV material is not available for use for surgical revision
- PLEASE REMEMBER TO SAVE A TISSUE SPECIMEN FOR THE STUDY SPONSOR in addition to following the standard pathology protocol per site specific policies.
Guidelines For Arteriovenous Access Intervention, Management, And Abandonment
The Clinical Events Committee (CEC) has developed a detailed set of access management guidelines for the AV access studies (HUMANITY and HAV ACCESS).
Content approved by WIRB 16 March, 2020
HAV Intervention Procedure Guidelines
Clinical Trial Synopsis-HUMANITY
Official Title of the Clinical Trial:
An Assessment of Humacyte’s Human Acellular Vessel in Patients Needing Renal Replacement Therapy: A Comparison with ePTFE Grafts as Conduits for Hemodialysis (HUMANITY™).
Patients with end-stage renal disease (kidney failure) who require hemodialysis, but have unsuitable vessels for creation of a dialysis fistula for access will be chosen to participate in this prospective, multicenter, multinational, randomized, comparative study. Patients will be implanted in the forearm or upper arm with either a Humacyte Vessel (HAV) or a dialysis graft, the standard of care. The 1:1 randomization (a 50/50 chance of receiving the HAV or standard graft) will occur during surgery once your surgeon has determined where the study conduit should be placed. All patients will be required to take daily aspirin (75 to 325 mg) unless they are already taking another antiplatelet agent (e.g., Plavix). Each patient will be followed by study specific visits through 2 years (24 months) of follow up after implantation (whether the vessel or graft is open and functioning or not). After 2 years, only subjects with an open and functioning access will be followed (while the access remains open) for up to 5 years (60 months) post-implantation at routine study visits
SCHEDULE OF STUDY SPECIFIC VISITS
- Screening Visit (up to 35 days prior to surgery date)
- Day 0 (Surgery day)
- Post op Day 7-15
- 1 month
- 2 months
- 3 months
- 6 months
- 9 months
- 1 year
- 18 months
- 2 years
- Visits will continue every 6 months from month 30 – 60 as long as the access remains open and functional
All visits include:
- A general physical exam
- Evaluation of the study access
- Documentation of:
- Problems
- Work done to the study access
- Perm cath placement
- Medications
Some visits will include:
- Ultrasound imaging of the study access
- Lab work
Humacyte Vessel
Phase II Clinical Trial Results
The following clinical data were adapted from the Humacyte Phase II clinical trial results as reported by Lawson, et al. The Lancet, May 2016. Two, single arm Phase II clinical trials were conducted in adults in the US and Poland to evaluate the safety and efficacy of the novel bioengineered HAV when implanted into the arms of patients with ESRD who were deemed not suitable for fistula creation to create a vascular access for dialysis. Primary endpoints were safety (freedom from immune response/infection, aneurysm, or mechanical failure, incidence of adverse events). Efficacy was assessed by primary, primary assisted and secondary patencies at 6 months. Secondary endpoints included patency and intervention rates at 12, 18 and 24 months, and changes in panel reactive antibodies (PRA) following HAV implantation. During the course of the trial, 60 HAVs were implanted into the arms of 60 patients at 6 centers across the US and Poland with planned 24 months of follow up. All patients in this report were followed for at least 1 year, or had a censoring event. Conclusion: The results of the Phase II clinical trials provide evidence of the potential safety and effectiveness of the bioengineered HAV when used for hemodialysis access as well as evidence of HAV repopulation with host vascular cells, but warrant further study in randomized controlled clinical trials.
US / POLAND
COMBINED
NUMBER OF PATIENTS IMPLANTED
60
PATENCY – NUMBER (%)
| PRIMARY PATENCY | 6 MONTHS | 36 (63%) |
|---|---|---|
| 12 MONTHS | 15 (28%) | |
| PRIMARY ASSISTED PATENCY | 6 MONTHS | 41 (73%) |
| 12 MONTHS | 20 (38%) | |
| SECONDARY PATENCY | 6 MONTHS | 54 (97%) |
| 12 MONTHS | 46 (89%) | |
INTERVENTIONS (PER PATIENT YEAR)
1.89
HAV INFECTION, NUMBER (%PPY)
1 (1.3%)
