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| ID | Type | Description | Link |
|---|---|---|---|
| 2U01HL088942-07 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Heart, Lung, and Blood Institute (NHLBI) | NIH |
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The main purpose of this research is to determine whether injecting mesenchymal precursor cells (MPC) into the heart during surgery to implant a left ventricular assist device (LVAD) is safe. MPCs are normally present in human bone marrow and have been shown to increase the development of blood vessels and new heart muscle cells in the heart. In addition, this research is being done to test whether injecting the MPCs into the heart is effective in improving heart function.
Intramyocardial injection of mesenchymal precursor cells (MPC) in patients with advanced heart failure who are treated with left ventricular assist device (LVAD) implantation may result in a renewable source of proliferating functional cardiomyocytes; induce development of capillaries and larger-size blood vessels to supply oxygen and nutrients to endogenous myocardium and newly-implanted cardiomyocytes; and release factors capable of paracrine signaling.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| MPC Intramyocardial Injection | Experimental | Intramyocardial injections of 150 million MPCs |
|
| Control Solution | Sham Comparator | Intramyocardial injections of 50% Alpha-MEM/42.5% ProFreeze NAO Freezing Medium/7.5% DMSO |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| MPC Intramyocardial Injection | Biological | Intramyocardial injection of 150 million mesenchymal precursor cells at the time of LVAD implantation |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Temporary Weans From LVAD Support Tolerated | functional status, defined by the number of temporary weans from LVAD support tolerated over the 6 months post-randomization. A successful wean is the ability to tolerate temporary weaning from LVAD support for 30 minutes without sustained symptoms of worsening heart failure. Wean failures are defined as inability to tolerate the temporary wean for 30 minutes; death; or patient too unstable, in the judgment of the primary heart failure cardiologist, to tolerate the wean attempt. | up to 6 months |
| Number of Participants With Adverse Events | Safety as assessed by number of study intervention-related adverse events | up to 6 months |
| Measure | Description | Time Frame |
|---|---|---|
| Physiologic Assessments | Echocardiographic assessments of the myocardial size and function by transthoracic echocardiography with LVAD at full support, and as tolerated following 6-Minute Walk Test (MWT) while weaned from LVAD support (for patients who tolerate wean from LVAD support for 30 minutes) | up to 12 months |
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Inclusion Criteria:
Exclusion Criteria:
Planned percutaneous LVAD implantation
Anticipated requirement for biventricular mechanical support
Concomitant arrhythmia ablation at time of LVAD implantation
-- Planned aortic valve intervention for aortic insufficiency at the time of LVAD implantation
Cardiothoracic surgery within 30 days prior to randomization
Spontaneous myocardial infarction related to ischemia due to a primary coronary event such as unstable plaque rupture, erosion or dissection within 30 days prior to randomization
Prior cardiac transplantation, LV reduction surgery, or cardiomyoplasty
Acute reversible cause of heart failure (e.g. myocarditis, profound hypothyroidism)
Stroke within 30 days prior to randomization
Platelet count < 100,000/ul within 24 hours prior to randomization
Acute infectious process: acute bacterial, fungal, or viral disease OR acute exacerbation of chronic infectious disease such as hepatitis
Presence of >10% anti-HLA antibody titers with known specificity to MPC donor HLA antigens
A known hypersensitivity to dimethyl sulfoxide (DMSO), murine, and/or bovine products
History of a known active malignancy within the past 3 years except for localized prostate cancer, cervical carcinoma in situ, breast cancer in situ, or nonmelanoma skin cancer that has been definitively treated
Presence of human immunodeficiency virus (HIV)
Received investigational intervention within 30 days prior to randomization
Treatment and/or an incomplete follow-up treatment of any investigational cell based therapy within 6 months prior to randomization
Active participation in other research therapy for cardiovascular repair/regeneration
Prior recipient of stem precursor cell therapy for cardiac repair
Pregnant or breastfeeding at time of randomization.
History of known or suspected hypercoagulable state in the opinion of the investigator
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| Name | Affiliation | Role |
|---|---|---|
| Patrick O'Gara, MD | Brigham and Women's Hospital | Study Chair |
| Richard Weisel, MD | Toronto General Hospital | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Southern California | Los Angeles | California | 90033 | United States | ||
| Stanford University School of Medicine |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30912838 | Derived | Yau TM, Pagani FD, Mancini DM, Chang HL, Lala A, Woo YJ, Acker MA, Selzman CH, Soltesz EG, Kern JA, Maltais S, Charbonneau E, Pan S, Marks ME, Moquete EG, O'Sullivan KL, Taddei-Peters WC, McGowan LK, Green C, Rose EA, Jeffries N, Parides MK, Weisel RD, Miller MA, Hung J, O'Gara PT, Moskowitz AJ, Gelijns AC, Bagiella E, Milano CA; Cardiothoracic Surgical Trials Network. Intramyocardial Injection of Mesenchymal Precursor Cells and Successful Temporary Weaning From Left Ventricular Assist Device Support in Patients With Advanced Heart Failure: A Randomized Clinical Trial. JAMA. 2019 Mar 26;321(12):1176-1186. doi: 10.1001/jama.2019.2341. |
| Label | URL |
|---|---|
| Cardiothoracic Surgical Network Website | View source |
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Screening started in 2014. First patient randomized in July 2015. Last patient randomized in August 2017.
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| ID | Title | Description |
|---|---|---|
| FG000 | MPC Intramyocardial Injection | MPC Intramyocardial Injection: Intramyocardial injection of 150 million mesenchymal precursor cells (MPCs) at the time of LVAD implantation |
| FG001 | Control Solution |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Aug 15, 2018 |
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|
| Control Solution | Drug |
|
|
| Histopathological Assessments of Myocardial Tissue |
| up to 12 months |
| Overall Survival | up to 12 months |
| Change in Quality of Life (QoL) | Quality of life will be assessed with the Kansas City Cardiomyopathy Questionnaire (KCCQ), a widely used tool in heart failure populations, and the Short Form 12 (SF12), a widely used overall health status measure. | 6 months and 12 months |
| Hopkins Verbal Learning Test | Cognitive performance will be assessed Hopkins Verbal Learning Test. Neurocognitive testing will be administered by clinical site personnel who have been trained and certified for test administration by the Neurocognitive Core lab personnel. | 3 months and 12 months |
| Trailmaking Tests A and B | Cognitive performance will be assessed using Trailmaking Tests A and B. Neurocognitive testing will be administered by clinical site personnel who have been trained and certified for test administration by the Neurocognitive Core lab personnel. | 3 months and 12 months |
| MCG Complex Figures | Cognitive performance will be assessed using the MCG Complex Figures. Neurocognitive testing will be administered by clinical site personnel who have been trained and certified for test administration by the Neurocognitive Core lab personnel. | 3 months and 12 months |
| Digit Span | Cognitive performance will be assessed using the MCG Complex Figures. Neurocognitive testing will be administered by clinical site personnel who have been trained and certified for test administration by the Neurocognitive Core lab personnel. | 3 months and 12 months |
| Digit Symbol Substitution Test | Cognitive performance will be assessed using the Digit Symbol Substitution Test. Neurocognitive testing will be administered by clinical site personnel who have been trained and certified for test administration by the Neurocognitive Core lab personnel. | 3 months and 12 months |
| Controlled Oral Word Association | Cognitive performance will be assessed using the Controlled Oral Word Association. Neurocognitive testing will be administered by clinical site personnel who have been trained and certified for test administration by the Neurocognitive Core lab personnel. | 3 months and 12 months |
| Length of Stay | Length of stay of index hospitalization | up to 12 months |
| Hospitalizations | Frequency and cause of readmissions | up to 12 months |
| Hospital Costs | Hospital resource use | up to 12 months |
| Functional Status | functional status, defined by the number of temporary weans from LVAD support tolerated | up to 12 months |
| Stanford |
| California |
| 94305 |
| United States |
| University of Maryland | Baltimore | Maryland | 21201 | United States |
| University of Michigan | Ann Arbor | Michigan | 48109 | United States |
| Henry Ford Hospital | Detroit | Michigan | 48202 | United States |
| Columbia University Medical Center | New York | New York | 10032 | United States |
| Montefiore Einstein Heart Center | The Bronx | New York | 10467 | United States |
| Duke University | Durham | North Carolina | 27710 | United States |
| Cleveland Clinic Foundation | Cleveland | Ohio | 44195 | United States |
| Ohio State University | Columbus | Ohio | 43210 | United States |
| University of Pennsylvania | Philadelphia | Pennsylvania | 19104 | United States |
| University of Pittsburgh | Pittsburgh | Pennsylvania | 15213 | United States |
| Baylor Research Institute | Plano | Texas | 75093 | United States |
| University of Utah | Salt Lake City | Utah | 84132 | United States |
| University of Virginia Health Systems | Charlottesville | Virginia | 22908 | United States |
| University of Wisconsin School of Medicine and Public Health | Madison | Wisconsin | 53726 | United States |
| University of Alberta Hospital | Edmonton | Alberta | T6G 2B7 | Canada |
| Toronto General Hospital | Toronto | Ontario | M5G 2C4 | Canada |
| Institut Universitaire de Cardiologie de Quebec (Hopital Laval) | Québec | Quebec | G1V 4G5 | Canada |
Control Solution: Intramyocardial injections of 50% Alpha-MEM/42.5% ProFreeze NAO Freezing Medium/7.5% DMSO
| COMPLETED |
|
| NOT COMPLETED |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | MPC Intramyocardial Injection | MPC Intramyocardial Injection: Intramyocardial injection of 150 million mesenchymal precursor cells (MPCs) at the time of LVAD implantation |
| BG001 | Control Solution | Control Solution: Intramyocardial injections of 50% Alpha-MEM/42.5% ProFreeze NAO Freezing Medium/7.5% DMSO |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Temporary Weans From LVAD Support Tolerated | functional status, defined by the number of temporary weans from LVAD support tolerated over the 6 months post-randomization. A successful wean is the ability to tolerate temporary weaning from LVAD support for 30 minutes without sustained symptoms of worsening heart failure. Wean failures are defined as inability to tolerate the temporary wean for 30 minutes; death; or patient too unstable, in the judgment of the primary heart failure cardiologist, to tolerate the wean attempt. | Posted | Mean | Standard Deviation | number of weans | up to 6 months |
|
|
| |||||||||||||||||||||||||||||
| Primary | Number of Participants With Adverse Events | Safety as assessed by number of study intervention-related adverse events | Posted | Count of Participants | Participants | up to 6 months |
|
| |||||||||||||||||||||||||||||||
| Secondary | Physiologic Assessments | Echocardiographic assessments of the myocardial size and function by transthoracic echocardiography with LVAD at full support, and as tolerated following 6-Minute Walk Test (MWT) while weaned from LVAD support (for patients who tolerate wean from LVAD support for 30 minutes) | Not Posted | up to 12 months | Participants | ||||||||||||||||||||||||||||||||||
| Secondary | Histopathological Assessments of Myocardial Tissue | Not Posted | up to 12 months | Participants | |||||||||||||||||||||||||||||||||||
| Secondary | Overall Survival | Not Posted | up to 12 months | Participants | |||||||||||||||||||||||||||||||||||
| Secondary | Change in Quality of Life (QoL) | Quality of life will be assessed with the Kansas City Cardiomyopathy Questionnaire (KCCQ), a widely used tool in heart failure populations, and the Short Form 12 (SF12), a widely used overall health status measure. | Not Posted | 6 months and 12 months | Participants | ||||||||||||||||||||||||||||||||||
| Secondary | Hopkins Verbal Learning Test | Cognitive performance will be assessed Hopkins Verbal Learning Test. Neurocognitive testing will be administered by clinical site personnel who have been trained and certified for test administration by the Neurocognitive Core lab personnel. | Not Posted | 3 months and 12 months | Participants | ||||||||||||||||||||||||||||||||||
| Secondary | Trailmaking Tests A and B | Cognitive performance will be assessed using Trailmaking Tests A and B. Neurocognitive testing will be administered by clinical site personnel who have been trained and certified for test administration by the Neurocognitive Core lab personnel. | Not Posted | 3 months and 12 months | Participants | ||||||||||||||||||||||||||||||||||
| Secondary | MCG Complex Figures | Cognitive performance will be assessed using the MCG Complex Figures. Neurocognitive testing will be administered by clinical site personnel who have been trained and certified for test administration by the Neurocognitive Core lab personnel. | Not Posted | 3 months and 12 months | Participants | ||||||||||||||||||||||||||||||||||
| Secondary | Digit Span | Cognitive performance will be assessed using the MCG Complex Figures. Neurocognitive testing will be administered by clinical site personnel who have been trained and certified for test administration by the Neurocognitive Core lab personnel. | Not Posted | 3 months and 12 months | Participants | ||||||||||||||||||||||||||||||||||
| Secondary | Digit Symbol Substitution Test | Cognitive performance will be assessed using the Digit Symbol Substitution Test. Neurocognitive testing will be administered by clinical site personnel who have been trained and certified for test administration by the Neurocognitive Core lab personnel. | Not Posted | 3 months and 12 months | Participants | ||||||||||||||||||||||||||||||||||
| Secondary | Controlled Oral Word Association | Cognitive performance will be assessed using the Controlled Oral Word Association. Neurocognitive testing will be administered by clinical site personnel who have been trained and certified for test administration by the Neurocognitive Core lab personnel. | Not Posted | 3 months and 12 months | Participants | ||||||||||||||||||||||||||||||||||
| Secondary | Length of Stay | Length of stay of index hospitalization | Not Posted | up to 12 months | Participants | ||||||||||||||||||||||||||||||||||
| Secondary | Hospitalizations | Frequency and cause of readmissions | Not Posted | up to 12 months | Participants | ||||||||||||||||||||||||||||||||||
| Secondary | Hospital Costs | Hospital resource use | Not Posted | up to 12 months | Participants | ||||||||||||||||||||||||||||||||||
| Secondary | Functional Status | functional status, defined by the number of temporary weans from LVAD support tolerated | Not Posted | up to 12 months | Participants |
6 months for adverse events 12 months for mortality
Trial specific protocol-defined adverse event
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | MPC Intramyocardial Injection | Intramyocardial injections of 150 million MPCs MPC Intramyocardial Injection: Intramyocardial injection of 150 million mesenchymal precursor cells at the time of LVAD implantation | 15 | 106 | 88 | 106 | 33 | 106 |
| EG001 | Control Solution | Intramyocardial injections of 50% Alpha-MEM/42.5% ProFreeze NAO Freezing Medium/7.5% DMSO Control Solution | 8 | 53 | 41 | 53 | 12 | 53 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Bleeding | General disorders | CTCAE (unspecified) | Systematic Assessment |
| |
| Sustained ventricular dysrhythmia requiring defibrillation or cardioversion | Cardiac disorders | CTCAE (unspecified) | Systematic Assessment |
| |
| Sustained supraventricular dysrhythmia requiring drug treatment or cardioversion | Cardiac disorders | CTCAE (unspecified) | Systematic Assessment |
| |
| Pump thrombus confirmed | Injury, poisoning and procedural complications | CTCAE (unspecified) | Systematic Assessment |
| |
| Pump thrombus suspected | Injury, poisoning and procedural complications | CTCAE (unspecified) | Systematic Assessment |
| |
| Nonpump thrombus related | Injury, poisoning and procedural complications | CTCAE (unspecified) | Systematic Assessment |
| |
| Minor device malfunction | Injury, poisoning and procedural complications | CTCAE (unspecified) | Systematic Assessment |
| |
| Hemolysis | Blood and lymphatic system disorders | CTCAE (unspecified) | Systematic Assessment |
| |
| Localized nondevice infection | Infections and infestations | CTCAE (unspecified) | Systematic Assessment |
| |
| Sepsis | Infections and infestations | CTCAE (unspecified) | Systematic Assessment |
| |
| Percutaneous site and/or pocket infection | Infections and infestations | CTCAE (unspecified) | Systematic Assessment |
| |
| Toxic metabolic encephalopathy | Nervous system disorders | CTCAE (unspecified) | Systematic Assessment |
| |
| Ischemic stroke | Nervous system disorders | CTCAE (unspecified) | Systematic Assessment |
| |
| Intracranial hemorrhage | Nervous system disorders | CTCAE (unspecified) | Systematic Assessment |
| |
| Transient ischemic attack | Nervous system disorders | CTCAE (unspecified) | Systematic Assessment |
| |
| Other neurological dysfunction | Nervous system disorders | CTCAE (unspecified) | Systematic Assessment |
| |
| Renal dysfunction | Renal and urinary disorders | CTCAE (unspecified) | Systematic Assessment |
| |
| Right heart failure | Cardiac disorders | CTCAE (unspecified) | Systematic Assessment |
| |
| Potential Inflammatory Responses | General disorders | CTCAE (unspecified) | Systematic Assessment |
| |
| Pericardial Fluid Collection | Cardiac disorders | CTCAE (unspecified) | Systematic Assessment |
| |
| Vasodilatory State | Cardiac disorders | CTCAE (unspecified) | Systematic Assessment |
| |
| Hepatic Dysfunction | Hepatobiliary disorders | CTCAE (unspecified) | Systematic Assessment |
| |
| Hypertension | Vascular disorders | CTCAE (unspecified) | Systematic Assessment |
| |
| MI (Non-perioperative) | Cardiac disorders | CTCAE (unspecified) | Systematic Assessment |
| |
| Psychiatric Episode | Psychiatric disorders | CTCAE (unspecified) | Systematic Assessment |
| |
| Respiratory Failure | Respiratory, thoracic and mediastinal disorders | CTCAE (unspecified) | Systematic Assessment |
| |
| Arterial Non-CNS Thromboembolism | Vascular disorders | CTCAE (unspecified) | Systematic Assessment |
| |
| Venous Thromboembolism Event | Blood and lymphatic system disorders | CTCAE (unspecified) | Systematic Assessment |
| |
| Wound Dehiscence | Injury, poisoning and procedural complications | CTCAE (unspecified) | Systematic Assessment |
| |
| Pleural Effusion | Respiratory, thoracic and mediastinal disorders | CTCAE (unspecified) | Systematic Assessment |
| |
| Sustained SVT dysrhytmia | Cardiac disorders | CTCAE (unspecified) | Systematic Assessment | Sustained supraventricular dysrhythmia requiring drug treatment or cardioversion |
|
| Localized nondevice infection | Infections and infestations | Systematic Assessment |
| ||
| Pleural Effusion | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Sustained supraventricular dysrhythmia | Cardiac disorders | Systematic Assessment | Sustained supraventricular dysrhythmia requiring drug treatment or cardioversion |
| |
| Localized nondevice infection | Infections and infestations | Systematic Assessment |
| ||
| Pleural Effusion | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Annetine Gelijns, PhD | Icahn School of Medicine at Mount Sinai | 212-659-9567 | annetine.gelijns@mssm.edu |
| Oct 30, 2019 |
| Prot_SAP_000.pdf |
| ID | Term |
|---|---|
| D006333 | Heart Failure |
| D009202 | Cardiomyopathies |
| D018754 | Ventricular Dysfunction |
| ID | Term |
|---|---|
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
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| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
|