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

Cardiovascular Diseases Clinical Trial

— TEVG-2  

Official title:

Prospective, Open-labeled, Single-arm Clinical Trial to Evaluate the Safety and Efficacy of the Second-generation Tissue Engineered Vascular Graft as Vascular Conduits for Extracardiac Total Cavopulmonary Connection.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04467671
• Other study ID #: IDE18703
• Secondary ID: 1UG3HL1486931UH3
• Status: Recruiting
• Phase: Phase 2
• Start date: July 15, 2020
• Est. completion date: August 2027

Study information

• Verified date: August 2023
• Source: Nationwide Children's Hospital
• Contact: Samantha Fichtner, BSN, RN
• Phone: 614-355-5764
• Email: samantha.fichtner[@]nationwidechildrens.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 24
• Est. completion date: August 2027
• Est. primary completion date: August 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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.

Related Conditions & MeSH terms

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

Intervention

Combination Product:
• Tissue Engineered Vascular Grafts
Patients will undergo EC TCPC interposition grafting with a tissue engineered vascular graft and serial magnetic resonance imaging (MRI)

Locations

Country	Name	City	State
United States	Nationwide Children's Hospital	Columbus	Ohio

Sponsors (4)

Lead Sponsor	Collaborator
Nationwide Children's Hospital	Gunze Limited, National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

References & Publications (6)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety and Tolerability of TEVG	Assessed through graft related complications as determined by serial echocardiogram	2 years
Primary	Safety and Tolerability of TEVG	Assessed through graft related complications as determined by serial MRI	2 years
Primary	Safety and Tolerability of TEVG	Assessed through adverse events	2 years
Secondary	Efficacy of TEVG	Evaluate graft performance based on MRI	2 years
Secondary	Efficacy of TEVG	Measured graft volume(mL) as determined by MRI	2 years
Secondary	Efficacy of TEVG	Measured graft length (mm) as determined by MRI	2 years