NCT03079401

Brief Summary

Patients under the age of 5, with a diagnosis of hypoplastic left heart syndrome (HLHS), unbalanced atrioventricular canal (uAVC), or borderline left heart who are undergoing staged LV recruitment following bidirectional Glenn (BDG) or undergoing BDG with plans for LV recruitment will be considered for enrollment in this study. Those patients enrolled in the study will be randomized to either the experimental arm or control arm of the study. Those patients randomized to the experimental arm will receive mesenchymal precursor cells (MPCs) injected directly into the LV endocardium during their LV recruitment or BDG procedure. Those patients randomized to the control arm will receive normal standard of care during their procedure with no injection of MPCs. It is believed that injection of MPCs will help improve the chances of those patients with single ventricle or borderline left ventricle being converted to biventricular circulation which could improve quality of life and longevity over palliation.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
19

participants targeted

Target at P25-P50 for phase_1

Timeline
Completed

Started Nov 2017

Longer than P75 for phase_1

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

March 8, 2017

Completed
6 days until next milestone

First Posted

Study publicly available on registry

March 14, 2017

Completed
9 months until next milestone

Study Start

First participant enrolled

November 27, 2017

Completed
5.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 19, 2022

Completed
1 year until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2024

Completed
Last Updated

April 21, 2023

Status Verified

April 1, 2023

Enrollment Period

5.1 years

First QC Date

March 8, 2017

Last Update Submit

April 20, 2023

Conditions

Hypoplastic Left Heart SyndromeAtrioventricular Canal

Keywords

biventricular conversion

Outcome Measures

Primary Outcomes (2)

  • Safety- Incidence of severe adverse events

    Subjects will be SAE free for 24 months following injection of MPCs (in comparison of treatment arm to control arm.

    24 months

  • Safety- Absence of PRA status change or local inflammation

    Subjects will be free from Panel Reactive Antibody (PRA) status change for 24 months following injection of MPCs (in comparison of treatment arm to control arm). If there is a PRA of \>5%, a donor specific antibody test will be completed,

    24 months

Secondary Outcomes (3)

  • Efficacy- rate of biventricular conversion

    12 months

  • Efficacy- improvement of LV end diastolic pressure

    12 months

  • Efficacy- improvement of LV mass/volume ratio

    12 months

Study Arms (2)

Treatment Arm

EXPERIMENTAL

Those randomized to the treatment arm will receive MPCs injected directly into the LV endocardium following clinical surgical maneuvers to recruit the LV (mitral valve repair, aortic valve repair, and/or resection of endocardial fibroelastosis) or BDG. MPCs will be delivered directly into the LV endocardium via a 23-25 gauge needle following completion of all surgical procedures. A total dose of 20 million cells will be delivered, divided evenly into \~11 injections of 50 µL each. The total volume is not to exceed 2.0 mL.

Biological: MPC; rexlemestrocel-L

Control Arm

NO INTERVENTION

Those subjects randomized to the control arm will receive standard LV recruitment or BDG with no injection.

Interventions

MPC; rexlemestrocel-LBIOLOGICAL

MPCs will be injected into the patient's myocardium during planned surgical procedures.

Also known as: Allogeneic Mesenchymal Precursor Cell
Treatment Arm

Eligibility Criteria

AgeUp to 5 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17)

You may qualify if:

  • Patients with a history of single ventricle palliation (Stage 1 palliation, PA band, or hybrid procedure) undergoing bidirectional Glenn (BDG) with simultaneous left ventricle (LV) recruitment procedures or those patients undergoing LV recruitment procedures will be considered for enrollment.

You may not qualify if:

  • Patients with current or history of myocardial tumors
  • Patients with aortic or mitral atresia
  • Patients with a history of high grade ventricular arrhythmias
  • Patients with a known allergy to dimethyl sulfoxide (DMSO)
  • Patient has known allergy to mouse and/or cow products.
  • Patient is prior recipient of stem cell therapy for cardiac repair.
  • Patient has received treatment and/or is within an incomplete follow-up treatment of any investigational cell based therapy within 6 months prior to randomization.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

Related Publications (4)

  • Emani SM, del Nido PJ. Strategies to maintain biventricular circulation in patients with high-risk anatomy. Semin Thorac Cardiovasc Surg Pediatr Card Surg Annu. 2013;16(1):37-42. doi: 10.1053/j.pcsu.2013.01.003.

    PMID: 23561816BACKGROUND

  • Emani SM, McElhinney DB, Tworetzky W, Myers PO, Schroeder B, Zurakowski D, Pigula FA, Marx GR, Lock JE, del Nido PJ. Staged left ventricular recruitment after single-ventricle palliation in patients with borderline left heart hypoplasia. J Am Coll Cardiol. 2012 Nov 6;60(19):1966-74. doi: 10.1016/j.jacc.2012.07.041. Epub 2012 Oct 10.

    PMID: 23062531BACKGROUND

  • Ascheim DD, Gelijns AC, Goldstein D, Moye LA, Smedira N, Lee S, Klodell CT, Szady A, Parides MK, Jeffries NO, Skerrett D, Taylor DA, Rame JE, Milano C, Rogers JG, Lynch J, Dewey T, Eichhorn E, Sun B, Feldman D, Simari R, O'Gara PT, Taddei-Peters WC, Miller MA, Naka Y, Bagiella E, Rose EA, Woo YJ. Mesenchymal precursor cells as adjunctive therapy in recipients of contemporary left ventricular assist devices. Circulation. 2014 Jun 3;129(22):2287-96. doi: 10.1161/CIRCULATIONAHA.113.007412. Epub 2014 Mar 28.

    PMID: 24682346BACKGROUND

  • Psaltis PJ, Carbone A, Nelson AJ, Lau DH, Jantzen T, Manavis J, Williams K, Itescu S, Sanders P, Gronthos S, Zannettino AC, Worthley SG. Reparative effects of allogeneic mesenchymal precursor cells delivered transendocardially in experimental nonischemic cardiomyopathy. JACC Cardiovasc Interv. 2010 Sep;3(9):974-83. doi: 10.1016/j.jcin.2010.05.016.

    PMID: 20850099BACKGROUND

MeSH Terms

Conditions

Hypoplastic Left Heart SyndromeEndocardial Cushion Defects

Condition Hierarchy (Ancestors)

Heart Defects, CongenitalCardiovascular AbnormalitiesCardiovascular DiseasesHeart DiseasesCongenital AbnormalitiesCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesHeart Septal Defects

Study Officials

  • Sitaram M Emani, MD

    Boston Children's Hospital

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Principal Investigator

Study Record Dates

First Submitted

March 8, 2017

First Posted

March 14, 2017

Study Start

November 27, 2017

Primary Completion

December 19, 2022

Study Completion

January 1, 2024

Last Updated

April 21, 2023

Record last verified: 2023-04

Data Sharing

IPD Sharing
Will not share

Locations

US(1)