Tissue Engineered Vascular Grafts for Heart Disease

(TEVG-2 Trial)

Overseen By Victoria Shay

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Nationwide Children's Hospital

Must not be taking: Bisphosphonates

Disqualifiers: Acute renal failure, Pacemaker, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Immediate post-operative period

24 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new type of blood vessel graft, known as Second-Generation Tissue Engineered Vascular Grafts, designed for people with specific heart conditions. The goal is to determine if these grafts are safe and effective for those needing extracardiac total cavopulmonary connection. Suitable candidates are patients already planning for this heart surgery and able to give informed consent. This trial does not suit those with urgent health needs, certain kidney problems, or other specific medical conditions. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial may require you to stop taking certain medications if they could interfere with the study, such as bisphosphonates (medications that prevent bone loss). It's best to discuss your current medications with the trial investigator to see if any changes are needed.

What prior data suggests that these tissue engineered vascular grafts are safe for use in heart disease?

Research has shown that second-generation tissue-engineered vascular grafts (TEVG) have promising results in early studies. These grafts have been tested in various situations, such as replacing parts of medium-sized arteries, and have demonstrated the ability to transform into living tissues capable of growth, which is encouraging.

However, some issues have been noted. The main problem is stenosis, where the grafts can become narrow, posing the biggest obstacle to wider use. Other potential issues include thrombosis, where blood clots may form in the graft.

Overall, these findings suggest that while the grafts have potential, safety concerns remain. The current trial phase aims to better understand the treatment's tolerability and safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for heart disease, which often involve lifestyle changes, medications, or invasive procedures like bypass surgery, second-generation tissue engineered vascular grafts offer a novel approach. These grafts are unique because they're designed to mimic the body's natural blood vessels, potentially reducing the risk of rejection and complications that accompany synthetic grafts or transplants from donors. Researchers are excited about this treatment because it promises to provide a more durable and biocompatible solution, potentially improving long-term outcomes for patients with heart disease.

What evidence suggests that Second-Generation Tissue Engineered Vascular Grafts might be an effective treatment for heart disease?

Research has shown that newer types of tissue-engineered blood vessel replacements, such as the Second-Generation Tissue Engineered Vascular Grafts studied in this trial, hold promise for treating heart conditions. These replacements have successfully replaced arteries and helped the body grow its own tissue. Studies have shown good results for medium-sized arteries, with fewer issues like blood clots. These replacements can grow and adapt with the patient, making them suitable for heart surgeries in children. Early findings suggest they can safely serve as pathways in heart procedures. ^{4 6 7 8 9}

Who Is on the Research Team?

Toshiharu Shinoka, MD/PhD

Principal Investigator

Nationwide Children's Hospital

Christopher Breuer, MD

Principal Investigator

Nationwide Children's Hospital

Mark Galantowicz, MD

Principal Investigator

Nationwide Children's Hospital

Are You a Good Fit for This Trial?

This trial is for children with certain heart defects who need a special surgery called extracardiac total cavopulmonary connection. They must be able to follow the study plan and not have urgent medical issues, pacemakers, severe heart valve problems, other serious health conditions, or need graft sizes outside of 12-24 mm. Kids with high lung blood pressure or abnormal veins can't join.

Inclusion Criteria

Patient and/or legal guardian must voluntarily provide informed consent/assent for participation in the study.

I am eligible for a specific heart surgery to improve blood flow.

Exclusion Criteria

Patient has a history of another condition or significant medical problem that, in the opinion of the investigator, precludes compliance with protocol-specified procedures.

Patient or parent/legal guardian is, in the opinion of the investigator, unable to comply with protocol evaluations.

You need a graft that is not between 12 and 24 millimeters in diameter.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients with single ventricle cardiac anomalies undergo EC TCPC using a tissue engineered conduit

Immediate post-operative period

In-patient surgical procedure

Follow-up

Participants are monitored for safety and effectiveness after treatment, including adverse events and graft performance

2 years

Regular follow-up visits at Nationwide Children's Hospital

Interim Analysis

Interim analysis to assess early graft-related complications in the first 6 enrolled patients

Up to 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Second-Generation Tissue Engineered Vascular Grafts

Trial Overview The study tests second-generation tissue engineered vascular grafts (TEVG) in kids needing heart surgery to connect large veins to their lungs. It's checking if these new grafts are safe and work well over two years without using different treatment groups.

How Is the Trial Designed?

Group I: Tissue Engineered Vascular Grafts Experimental Treatment 1 Intervention

Second-Generation Tissue Engineered Vascular Grafts is already approved in United States for the following indications:

Approved in United States as Second-Generation TEVG for:

• Extracardiac Total Cavopulmonary Connection

Who Is Running the Clinical Trial?

Nationwide Children's Hospital

Lead Sponsor

Trials

354

Recruited

5,228,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Gunze Limited

Collaborator

Trials

3

Recruited

30+

Published Research Related to This Trial

Tissue-engineered vascular grafts (TEVGs) show promise in overcoming the limitations of conventional synthetic grafts, such as poor remodeling and patency issues, by utilizing biologically active cells and biodegradable scaffolds.

Recent advancements in TEVG technology, including improved scaffold materials and design, have led to successful clinical trials, indicating their potential for clinical applications and the development of 'off-the-shelf' solutions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tissue engineered vascular grafts: current state of the field. Ong, CS., Zhou, X., Huang, CY., et al.[2018]

Small-diameter tissue-engineered vascular grafts (TEVGs) are still not widely used in clinical settings, despite significant advancements in tissue engineering, highlighting a critical unmet need in medical treatments.

The review emphasizes the potential role of stem cells in developing TEVGs and suggests future research directions to enhance the viability and effectiveness of these grafts for clinical applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stem cells for tissue engineered vascular bypass grafts. Askari, F., Solouk, A., Shafieian, M., et al.[2018]

Tissue-engineered vascular grafts (TEVGs) show potential for creating functional blood vessels in children, with a study using a lamb model revealing that the polymer scaffold loses structural integrity within 26 weeks, while fragments can last up to 52 weeks.

Neotissue formation initially results from an inflammatory response to the scaffold, but as it degrades, the remodeling process shifts to being driven by mechanical forces, ultimately leading to a neovessel that behaves like a natural blood vessel and supports biological growth.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tissue engineered vascular grafts transform into autologous neovessels capable of native function and growth. Blum, KM., Zbinden, JC., Ramachandra, AB., et al.[2023]

In a study involving 25 patients with single ventricle physiology, tissue-engineered vascular grafts were successfully implanted as conduits, showing no graft-related mortality over a mean follow-up of 5.8 years.

The main issue observed was graft stenosis, which occurred in four patients but was treatable with percutaneous angioplasty, indicating that while the grafts are generally safe, monitoring for stenosis is essential.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Late-term results of tissue-engineered vascular grafts in humans. Hibino, N., McGillicuddy, E., Matsumura, G., et al.[2022]

Tissue-engineered vascular grafts (TEVGs) show potential advantages over traditional synthetic grafts, including reduced complications and improved integration with the body.

Current research, including both animal and human studies, indicates promising results for TEVGs, but further development is necessary before they can be widely adopted as replacements for conventional grafts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Current Status of Tissue-Engineered Vascular Grafts. Jaspan, VN., Hines, GL.[2015]

Endothelialization is crucial for preventing thrombosis in tissue-engineered vascular grafts (TEVGs), especially those with small diameters (<6 mm), which are prone to complications after transplantation.

The review highlights the importance of selecting appropriate types of endothelialization and seed cells to enhance the long-term success and patency rates of TEVGs, suggesting that tailored approaches could improve outcomes based on graft size and length.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selection of different endothelialization modes and different seed cells for tissue-engineered vascular graft. Cai, Q., Liao, W., Xue, F., et al.[2021]

The first clinical trial of tissue engineered vascular grafts (TEVG) using autologous bone marrow-derived cells showed an excellent safety profile, indicating that this approach is safe for patients with cardiovascular diseases.

However, about 16% of the grafts experienced stenosis (narrowing) within the first seven years, highlighting a significant complication that needs further research to improve the design and function of future TEVGs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vascular tissue engineering: towards the next generation vascular grafts. Naito, Y., Shinoka, T., Duncan, D., et al.[2011]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04467671

NCT04467671 | Two-Year Study of the Safety and Efficacy ... A single arm clinical trial evaluating the safety and efficacy of the second generation TEVG as vascular conduits for extracardiac total cavopulmonary ...

2. reporter.nih.gov reporter.nih.gov/project-details/10589938

Project Details - NIH RePORTER In this study, we will evaluate the short-term (2 year) safety and efficacy of a second-generation TEVG for use as an extracardiac conduit in children with ...

3. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1002/mba2.88

Tissue‐engineered vascular grafts for cardiovascular ... These materials showed promising results in aorto-iliac replacements and medium-sized arteries (6–8 mm). Complications such as, thrombosis and ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9974789/

Tissue Engineering of Vascular Grafts: A Case Report ... The fundamental premise underlying our work is that tissue engineering can augment congenital heart surgery by regenerating autologous cardiovascular neotissue ...

5. withpower.com withpower.com/trial/phase-3-heart-defects-congenital-6-2020-90ca9?condition=Single+Ventricle+Heart&overallStatus=Recruiting&hasNoPlacebo=false

Tissue Engineered Vascular Grafts for Heart Disease A single arm clinical trial evaluating the safety and efficacy of the second generation TEVG as vascular conduits for extracardiac total cavopulmonary ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04467671

NCT04467671 | Two-Year Study of the Safety and Efficacy ... A single arm clinical trial evaluating the safety and efficacy of the second generation TEVG as vascular conduits for extracardiac total cavopulmonary ...

7. reporter.nih.gov reporter.nih.gov/search/jfexWcl_ykqPLooUp6cgaA/project-details/10589938

breuer, christopher kane In this study, we will evaluate the short-term (2 year) safety and efficacy of a second-generation TEVG for use as an extracardiac conduit in children with ...

8. jacc.org jacc.org/doi/10.1016/j.jacbts.2025.04.008

Tissue Engineered Vascular Grafts: A Quarter Century ... The pooled results from both trials identified TEVG stenosis as the main graft-related complication limiting broader clinical adoption of this ...

9. ahajournals.org ahajournals.org/doi/10.1161/ATVBAHA.122.318236

Tissue Engineering of Vascular Grafts: A Case Report ... Results of our first-in-human study demonstrated feasibility as the TEVG transformed into a living vascular graft having an ability to grow, ...