Two-Year Study of the Safety and Efficacy of the Second-Generation Tissue Engineered Vascular Grafts

NCT ID: NCT04467671

Last Updated: 2025-06-27

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-07-15
• Study Completion Date: 2027-08-31

Brief Summary

A single arm clinical trial evaluating the safety and efficacy of the second generation TEVG as vascular conduits for extracardiac total cavopulmonary connection.

Detailed Description

This investigation is a prospective, open-labeled clinical trial determining the safety of the use of tissue engineered vascular grafts as conduits for EC TCPC. Patients will be monitored for adverse events (AE) and serious adverse events (SAE). Special attention will be paid to the incidence of stenosis. We will determine graft-related morbidity and mortality for the second generation TEVGs which will include any post-operative complication such as any aneurismal dilation, stenosis, thromboembolic or infectious event that requires treatment and is thought to be caused by the graft as determined by the investigators and confirmed by the data safety monitoring board. The graft related complication rates will be compared between the first and second generation TEVGs. An interim analysis will be performed to assess the incidence of early (<6 month) graft-related complications in the first 6 enrolled patients. Safety and tolerability will be assessed through serial imaging, to determine the effect of growth and remodeling on graft performance through echocardiography and 4-dimensional MRI. All appropriate patients requiring EC TCPC who meet study inclusion/exclusion criteria will be evaluated for enrollment in the clinical trial. All enrolled subjects will be required to have follow-up visits at Nationwide Children's Hospital for a minimum of 2 years following implant. After obtaining informed consent for the patient's parents, patients with single ventricle cardiac anomalies will undergo EC TCPC using a tissue engineered conduit. Post-operative care and monitoring will follow an established, standardized, clinical algorithm in which the patient's clinical status including complications and measurements of graft function will be serially evaluated and recorded over a two year period using physical examination, echocardiography, and MRI.

Conditions

HLH - Hypoplastic Left Heart Syndrome; DORV; DILV - Double Inlet Left Ventricle; Mitral Atresia; Tricuspid Atresia; Unbalanced AV Canal; Single-ventricle; Heart Defects, Congenital; Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Tissue Engineered Vascular Grafts

Group Type: EXPERIMENTAL

Tissue Engineered Vascular Grafts

Intervention Type: COMBINATION_PRODUCT

Patients will undergo EC TCPC interposition grafting with a tissue engineered vascular graft and serial magnetic resonance imaging (MRI)

Interventions

Tissue Engineered Vascular Grafts

Patients will undergo EC TCPC interposition grafting with a tissue engineered vascular graft and serial magnetic resonance imaging (MRI)

Intervention Type: COMBINATION_PRODUCT

Eligibility Criteria

Inclusion Criteria

• Patients will be eligible for inclusion in the study if they meet all of the following criteria.

1. Patient must be a candidate to undergo an extracardiac total cavopulmonary connection.

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

Exclusion Criteria

• Patients will be excluded from participation in the study if they meet any of the following criteria.

1. Patient has an urgent/emergent operative status.

2. Patient has acute renal failure or renal insufficiency in the opinion of the investigator

3. Patient requires a graft less than 12 mm or greater than 24 mm in diameter.

4. Patient has a pacemaker.

5. Patient has pulmonary vascular resistance greater than 4 um2 (u=Wood's units)

6. Patient has abnormal venous drainage (interrupted inferior vena cava [IVC]).

7. Patient presents with significant atrio-ventricular valve regurgitation that in the opinion of the investigator, makes them ineligible.

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

9. Patients taking any medications that in the opinion of the Investigator could interfere with the TEVG, including bisphosphonates (i.e. Clodronate or Zoledronate).

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

11. Preoperative hemoglobin <11.0 mg/dL at time of patient's pre-admission testing.

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

Gunze Limited

OTHER

Sponsor Role: collaborator

National Institutes of Health (NIH)

NIH

Sponsor Role: collaborator

Nationwide Children's Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Christopher Breuer, MD

Role: STUDY_CHAIR

Nationwide Children's Hospital

Toshiharu Shinoka, MD/PhD

Role: STUDY_CHAIR

Nationwide Children's Hospital

Mark Galantowicz, MD

Role: PRINCIPAL_INVESTIGATOR

Nationwide Children's Hospital

Locations

Nationwide Children's Hospital

Columbus, Ohio, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Samantha Fichtner, BSN, RN

Role: CONTACT

samantha.fichtner@nationwidechildrens.org

614-355-5764

Victoria Shay

Role: CONTACT

victoria.shay@nationwidechildrens.org

Facility Contacts

Samantha Fichtner, BSN, RN

Role: primary

samantha.fichtner@nationwidechildrens.org

614-355-5764

Victoria Shay

Role: backup

victoria.shay@nationwidechildrens.org

References

Drews JD, Pepper VK, Best CA, Szafron JM, Cheatham JP, Yates AR, Hor KN, Zbinden JC, Chang YC, Mirhaidari GJM, Ramachandra AB, Miyamoto S, Blum KM, Onwuka EA, Zakko J, Kelly J, Cheatham SL, King N, Reinhardt JW, Sugiura T, Miyachi H, Matsuzaki Y, Breuer J, Heuer ED, West TA, Shoji T, Berman D, Boe BA, Asnes J, Galantowicz M, Matsumura G, Hibino N, Marsden AL, Pober JS, Humphrey JD, Shinoka T, Breuer CK. Spontaneous reversal of stenosis in tissue-engineered vascular grafts. Sci Transl Med. 2020 Apr 1;12(537):eaax6919. doi: 10.1126/scitranslmed.aax6919.

Reference Type: BACKGROUND

PMID: 32238576 (View on PubMed)

Ruiz-Rosado JD, Lee YU, Mahler N, Yi T, Robledo-Avila F, Martinez-Saucedo D, Lee AY, Shoji T, Heuer E, Yates AR, Pober JS, Shinoka T, Partida-Sanchez S, Breuer CK. Angiotensin II receptor I blockade prevents stenosis of tissue engineered vascular grafts. FASEB J. 2018 Jun 15;32(12):fj201800458. doi: 10.1096/fj.201800458. Online ahead of print.

Reference Type: BACKGROUND

PMID: 29906242 (View on PubMed)

Lee YU, Mahler N, Best CA, Tara S, Sugiura T, Lee AY, Yi T, Hibino N, Shinoka T, Breuer C. Rational design of an improved tissue-engineered vascular graft: determining the optimal cell dose and incubation time. Regen Med. 2016 Mar;11(2):159-67. doi: 10.2217/rme.15.85. Epub 2016 Feb 29.

Reference Type: BACKGROUND

PMID: 26925512 (View on PubMed)

Kurobe H, Tara S, Maxfield MW, Rocco KA, Bagi PS, Yi T, Udelsman BV, Dean EW, Khosravi R, Powell HM, Shinoka T, Breuer CK. Comparison of the biological equivalence of two methods for isolating bone marrow mononuclear cells for fabricating tissue-engineered vascular grafts. Tissue Eng Part C Methods. 2015 Jun;21(6):597-604. doi: 10.1089/ten.TEC.2014.0442. Epub 2014 Dec 29.

Reference Type: BACKGROUND

PMID: 25397868 (View on PubMed)

Kurobe H, Maxfield MW, Naito Y, Cleary M, Stacy MR, Solomon D, Rocco KA, Tara S, Lee AY, Sinusas AJ, Snyder EL, Shinoka T, Breuer CK. Comparison of a closed system to a standard open technique for preparing tissue-engineered vascular grafts. Tissue Eng Part C Methods. 2015 Jan;21(1):88-93. doi: 10.1089/ten.TEC.2014.0160.

Reference Type: BACKGROUND

PMID: 24866863 (View on PubMed)

Hibino N, McGillicuddy E, Matsumura G, Ichihara Y, Naito Y, Breuer C, Shinoka T. Late-term results of tissue-engineered vascular grafts in humans. J Thorac Cardiovasc Surg. 2010 Feb;139(2):431-6, 436.e1-2. doi: 10.1016/j.jtcvs.2009.09.057.

Reference Type: BACKGROUND

PMID: 20106404 (View on PubMed)

Other Identifiers

5UH3HL148693

Identifier Type: NIH

Identifier Source: secondary_id

View Link

IDE18703

Identifier Type: -

Identifier Source: org_study_id