HLH - Hypoplastic Left Heart SyndromePhase 2TEVG-2NCT04467671
Two-Year Study of the Safety and Efficacy of the Second-Generation Tissue Engineered Vascular Grafts
A Phase 2 study testing Tissue Engineered Vascular Grafts in people with HLH - Hypoplastic Left Heart Syndrome and DORV, run by Nationwide Children's Hospital at 1 site in United States.
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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- HLH - Hypoplastic Left Heart Syndrome, DORV, DILV - Double Inlet Left Ventricle
- What is being tested?
- Tissue Engineered Vascular Grafts
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Jul 2020to Aug 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patients will be eligible for inclusion in the study if they meet all of the following criteria.
- Patient must be a candidate to undergo an extracardiac total cavopulmonary connection.
- Patient and/or legal guardian must voluntarily provide informed consent/assent for participation in the study.
Who cannot join
- Patients will be excluded from participation in the study if they meet any of the following criteria.
- Patient has an urgent/emergent operative status.
- Patient has acute renal failure or renal insufficiency in the opinion of the investigator
- Patient requires a graft less than 12 mm or greater than 24 mm in diameter.
- Patient has a pacemaker.
- Patient has pulmonary vascular resistance greater than 4 um2 (u=Wood's units)
Show all 12Show fewer
- Patient has abnormal venous drainage (interrupted inferior vena cava [IVC]).
- Patient presents with significant atrio-ventricular valve regurgitation that in the opinion of the investigator, makes them ineligible.
- Patient has a history of another condition or significant medical problem that, in the opinion of the investigator, precludes compliance with protocol-specified procedures.
- Patients taking any medications that in the opinion of the Investigator could interfere with the TEVG, including bisphosphonates (i.e. Clodronate or Zoledronate).
- Patient or parent/legal guardian is, in the opinion of the investigator, unable to comply with protocol evaluations.
- Preoperative hemoglobin <11.0 mg/dL at time of patient's pre-admission testing.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Victoria Shay contact
United States1 site, 1 recruiting
- Recruiting
Nationwide Children's Hospital
Columbus, Ohio, 43205
Samantha Fichtner, BSN, RN, 614-355-5764, samantha.fichtner@nationwidechildrens.org
Victoria Shay, victoria.shay@nationwidechildrens.org
About this study
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.
A single arm clinical trial evaluating the safety and efficacy of the second generation TEVG as vascular conduits for extracardiac total cavopulmonary connection.
Read the 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
- Being tested
- Tissue Engineered Vascular Grafts
- Keywords
- Fontan, TEVG, Tissue Engineered Vascular Graft
- Medical subject headings
- Hypoplastic Left Heart Syndrome, Tricuspid Atresia, Univentricular Heart, Heart Defects, Congenital, Cardiovascular Abnormalities, Cardiovascular Diseases, Heart Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tissue Engineered Vascular GraftsCombination product
Patients will undergo EC TCPC interposition grafting with a tissue engineered vascular graft and serial magnetic resonance imaging (MRI)
| Study group | Role | What they receive |
|---|---|---|
| Tissue Engineered Vascular Grafts | Experimental | Not described Receives: Combination Product: Tissue Engineered Vascular Grafts |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and Tolerability of TEVG
Assessed through graft related complications as determined by serial echocardiogram
Measured: 2 years
Safety and Tolerability of TEVG
Assessed through graft related complications as determined by serial MRI
Measured: 2 years
Safety and Tolerability of TEVG
Assessed through adverse events
Measured: 2 years
Secondary outcomes (3)
Efficacy of TEVG
Evaluate graft performance based on MRI
Measured: 2 years
Efficacy of TEVG
Measured graft volume(mL) as determined by MRI
Measured: 2 years
Efficacy of TEVG
Measured graft length (mm) as determined by MRI
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jul 2020
- Study start15 Jul 2020
- Primary completionAug 2026 (estimated)
- Study completionAug 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for HLH - Hypoplastic Left Heart SyndromeStudies of the same condition, open and under way.
- More trials run by Nationwide Children's HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Nationwide Children's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI), Gunze Limited, National Institutes of Health (NIH)
- Responsible party
- Sponsor
- Investigators
- Christopher Breuer, MD, Study chair, Nationwide Children's HospitalToshiharu Shinoka, MD/PhD, Study chair, Nationwide Children's HospitalMark Galantowicz, MD, Principal investigator, Nationwide Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04467671
- Sponsor's protocol ID
- IDE18703
- Other IDs
- 5UH3HL148693
- Acronym
- TEVG-2
- Status last verified
- Jun 2025
- First submitted
- 30 Jun 2020
- Last updated
- 27 Jun 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- Yes: Biological Samples: We plan to make available representative samples of the bone marrow-derived mononuclear cells and seeded scaffold to a NIH-designated entity (RM Innovation Catalyst) for in depth and independent characterization. Specifically, for each TEVG manufactured, 1 ml of bone marrow-derived mononuclear cells and a 5mm x 5mm section of the seeded scaffold will be sampled, packed, and transported to the RM Innovation Catalyst per their instructions. In addition, copies of the batch record and completed certificate of analysis will be forwarded to the NIH-designated laboratory.
Publications
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.
PubMed 32238576Ruiz-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.
PubMed 29906242Lee 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.
PubMed 26925512Kurobe 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.
PubMed 25397868Kurobe 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.
PubMed 24866863Hibino 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.
PubMed 20106404
Study at a glance
From the registry record, last updated by the sponsor on 27 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT04467671
- Acronym / sponsor ID
- TEVG-2 / IDE18703
- Conditions
- HLH - Hypoplastic Left Heart Syndrome, DORV, DILV - Double Inlet Left Ventricle, Mitral Atresia, Tricuspid Atresia, Unbalanced AV Canal
- Keywords
- Fontan, TEVG, Tissue Engineered Vascular Graft
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 24 participants (estimated)
- Lead sponsor
- Nationwide Children's HospitalUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI), Gunze Limited, National Institutes of Health (NIH)
- Study start
- 15 Jul 2020 (actual)
- Primary completion
- Aug 2026 (estimated)
- Study completion
- Aug 2027 (estimated)
- First posted
- 13 Jul 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Tissue Engineered Vascular Grafts | Experimental | Combination Product: Tissue Engineered Vascular Grafts |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- Patients will be eligible for inclusion in the study if they meet all of the following criteria.
Key exclusion criteria (12 listed)
- Patients will be excluded from participation in the study if they meet any of the following criteria.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tissue Engineered Vascular GraftsPatients will undergo EC TCPC interposition grafting with a tissue engineered vascular graft and serial magnetic resonance imaging (MRI) | Combination product | Tissue Engineered Vascular Grafts |
Primary outcome
Safety and Tolerability of TEVG
Time frame: 2 years
Assessed through graft related complications as determined by serial echocardiogram
Safety and Tolerability of TEVG
Time frame: 2 years
Assessed through graft related complications as determined by serial MRI
Safety and Tolerability of TEVG
Time frame: 2 years
Assessed through adverse events
3 secondary outcomes
Efficacy of TEVG
Time frame: 2 years
Efficacy of TEVG
Time frame: 2 years
Efficacy of TEVG
Time frame: 2 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jun 2025.
- Background: PubMed 32238576Drews 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.
- Background: PubMed 29906242Ruiz-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.
- Background: PubMed 26925512Lee 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.
- Background: PubMed 25397868Kurobe 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.
- Background: PubMed 24866863Kurobe 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.
- Background: PubMed 20106404Hibino 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.
- Individual participant dataSharing planned: Yes. Biological Samples: We plan to make available representative samples of the bone marrow-derived mononuclear cells and seeded scaffold to a NIH-designated entity (RM Innovation Catalyst) for in depth and independent characterization. Specifically, for each TEVG manufactured, 1 ml of bone marrow-derived mononuclear cells and a 5mm x 5mm section of the seeded scaffold will be sampled, packed, and transported to the RM Innovation Catalyst per their instructions. In addition, copies of the batch record and completed certificate of analysis will be forwarded to the NIH-designated laboratory.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Victoria Shay contact
Christopher Breuer, MD study chair
Nationwide Children's Hospital
Toshiharu Shinoka, MD/PhD study chair
Nationwide Children's Hospital
Mark Galantowicz, MD principal investigator
Nationwide Children's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Tissue Engineered Vascular Grafts in people with HLH - Hypoplastic Left Heart Syndrome and DORV, run by Nationwide Children's Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 27 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Samantha Fichtner, BSN, RN (614-355-5764, samantha.fichtner@nationwidechildrens.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety and Tolerability of TEVG (time frame: 2 years). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04467671, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jun 2025.