Prospective Randomized Study of Mesenchymal Stem Cell Therapy in Patients Undergoing Cardiac Surgery (PROMETHEUS) (PROMETHEUS)
19. august 2019 opdateret af: Joshua M Hare
A Phase I/II, Randomized, Double-Blinded, Placebo-Controlled Study of the Safety and Efficacy of Intramyocardial Injection of Autologous Human Mesenchymal Stem Cells (MSCs) in Patients With Chronic Ischemic Left Ventricular Dysfunction Secondary to Myocardial Infarction (MI) Undergoing Cardiac Surgery for Coronary Artery Bypass Grafting (CABG)
Heart attacks are a leading cause of death in both men and women in the United States.
When a person has a heart attack, blood is unable to reach a certain area of the heart, and if the blood supply is not re-established quickly, that area of the heart can suffer permanent damage.
While recovery from a heart attack can be managed through medications and lifestyle changes, these treatments can not reverse the original damage to the heart.
Current research is focusing on the development of cell-based therapies using stem cells to repair organs that have been irreversibly damaged by disease.
A specific form of stem cells, called adult mesenchymal stem cells (MSCs), has shown promise for heart repair.
This study will evaluate the safety and effectiveness of injecting MSCs into the heart to repair and restore heart function in people who have had a heart attack and who are having heart surgery for coronary artery bypass grafting (CABG).
Studieoversigt
Status
Afsluttet
Intervention / Behandling
Detaljeret beskrivelse
Participation in this study will last 18 months. Potential participants will undergo initial screening 5 to 7 weeks prior to CABG surgery. Screening will include a physical exam, blood draw, pregnancy test, questions about medical history, current medications, and alcohol or drug use, an electrocardiogram (ECG), magnetic resonance imaging (MRI) of the heart, questionnaires, an echocardiogram and a computed tomography (CT) scan. Eligible participants will then undergo two baseline visits within 6 weeks of their scheduled surgery. Baseline Visit 1 will consist of vital sign measurements, a bone marrow aspiration to obtain MSCs and a blood draw for a biomarker test. Baseline Visit 2 will include treadmill test, 6-minute walk test, pulmonary function (FEV1) study and a 48 Hour Ambulatory ECG. After the second baseline visit, participants will be assigned randomly to receive either MSCs or placebo after surgery.
On the day of surgery, once all of the bypass grafts have been placed, a high or low dose of MSCs or placebo will be injected into a damaged area of the heart that did not receive a bypass graft. After receiving the injections, participants will remain in the hospital for up to 7 days. During this stay, participants will undergo a daily blood draw, urine test, ECG, and ambulatory ECG monitoring for the first 96 hours after surgery.
Upon being discharged, participants will return for monthly visits for 6 months and for follow-up visits 12 and 18 months after surgery. These visits will repeat most initial screening and baseline tests. There will be one additional visit 14 days after surgery, which will include questions about side effects, a physical exam, and a 48-hour ambulatory ECG.
Undersøgelsestype
Interventionel
Tilmelding (Faktiske)
9
Fase
- Fase 2
- Fase 1
Kontakter og lokationer
Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.
Studiesteder
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Florida
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Miami, Florida, Forenede Stater, 33136
- University of Miami Miller School of Medicine
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Maryland
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Baltimore, Maryland, Forenede Stater, 21205
- Johns Hopkins University School Of Medicine
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Deltagelseskriterier
Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.
Berettigelseskriterier
Aldre berettiget til at studere
21 år til 80 år (Voksen, Ældre voksen)
Tager imod sunde frivillige
Ingen
Køn, der er berettiget til at studere
Alle
Beskrivelse
Inclusion Criteria:
- Diagnosis of chronic ischemic heart failure caused by a heart attack
- Scheduled to undergo cardiac surgery for CABG
- Ejection fraction between 15% and 50%
- Presence of an akinetic or dyskinetic region by standard imaging
Exclusion Criteria:
- Glomerular filtration rate of less than 50 mL/min/1.73m2 at study entry
- Contraindication to performance of an MRI scan
- Bone marrow dysfunction, as evidenced by a 20% or more deviation from normal hematocrit, white blood cell count, or platelet values without another explanation
- A coagulopathy condition not due to a reversible cause (i.e., Coumadin)
- Known, serious radiographic contrast allergy
- Known allergies to penicillin or streptomycin
- Organ transplant recipient
- Clinical history of malignancy within 5 years of study entry (e.g., patients with prior malignancy must be disease free for 5 years), except curatively treated basal cell carcinoma, squamous cell carcinoma, or cervical carcinoma
- Non-cardiac condition that limits lifespan to less than 1 year
- On chronic therapy with immunosuppressant medication
- Serum positive for HIV, hepatitis B, or hepatitis C
- Female who is pregnant, nursing, or of child-bearing potential and not practicing effective birth control methods
Studieplan
Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: Randomiseret
- Interventionel model: Parallel tildeling
- Maskning: Dobbelt
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
|---|---|
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Eksperimentel: Lower dose mesenchymal stem cell (MSC) injection
Participants will receive lower dose mesenchymal stem cell injections for a total of 2 x 10^7 cells
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Participants will receive between 10 and 20 intramyocardial injections of 2 million MSCs per 0.25-0.5 cubic centimeter (cc) for a total of 2 x 10^7 cells.
The injections will be administered following completion of CABG surgery.
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Eksperimentel: Higher dose MSC injection
Participants will receive higher dose of mesenchymal stem cell injections for a total of 2 x 10^8 cells
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Participants will receive between 10 and 20 intramyocardial injections of 20 million MSCs per 0.25-0.5 cc for a total of 2 x 10^8 cells.
The injections will be administered following completion of CABG surgery.
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Placebo komparator: (3) Placebo
Participants will receive placebo injections
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Participants will receive between 10 and 20 placebo injections that consist of phosphate buffered saline (PBS) and 1% human serum albumin (HSA).
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Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
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Number of Patients With Serious Adverse Events
Tidsramme: 12 Months
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Six-month post-CABG surgery serious adverse event (SAE) proportion of patients experiencing a composite of sustained ventricular arrhythmias, (lasting longer than 15 seconds), with hemodynamic compromise, sudden unexpected death at six months, ectopic tissue formation at 12 months by chest/abdomen/pelvis CT exam.
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12 Months
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Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
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Change in Infarct Scar Size (ISS) Over 18 Month Period
Tidsramme: Baseline, 6 Months, 18 Months
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Change in infarct scar size (ISS) between baseline and 6-month and 18 month visits as determined by delayed contrast-enhanced MRI.
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Baseline, 6 Months, 18 Months
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Left Ventricular Function (LVF) in Region of MSC Injection
Tidsramme: Assessed at Baseline and 18 Months
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The Left Ventricular Function differences in the region of MSC injection were evaluated.
LVF is evaluated via ECHO as the percentage of ejected blood.
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Assessed at Baseline and 18 Months
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Regional Left Ventricular Wall Thickening
Tidsramme: Assessed at Baseline and 18 months
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Difference between baseline and 18 month regional left ventricular wall thickening as determined by MRI.
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Assessed at Baseline and 18 months
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Left Ventricular End Diastolic Wall Thickness
Tidsramme: Assessed at Baseline and 18 months
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Difference between the baseline and 18 month left ventricular end diastolic wall thickness as determined by MRI and echocardiogram.
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Assessed at Baseline and 18 months
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Change in Left Ventricular End Diastolic and Systolic Volume
Tidsramme: Baseline, 6 Months, 18 Months
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Change in left ventricular end diastolic and systolic volume as determined by MRI and echocardiogram.
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Baseline, 6 Months, 18 Months
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Change in Left Ventricular Ejection Fraction
Tidsramme: Baseline to 6 Months, Baseline to 18 Months
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Change between baseline to 6-month and 18-month left ventricular ejection fraction (LVEF) as determined by MRI and echocardiogram.
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Baseline to 6 Months, Baseline to 18 Months
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Change in Peak Volume Oxygen
Tidsramme: Baseline, 6 Months, 18 Months
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Change in Peak VO2 as determined by treadmill test (mL/mg/min) from Baseline to 6 and from baseline to 18 months
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Baseline, 6 Months, 18 Months
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Change in Six Minute Walk Test
Tidsramme: Baseline, 6 Months, 18 Months
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Change in Six Minute Walk Test (in meters) from Baseline to 6 Months and Baseline to 18 Months
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Baseline, 6 Months, 18 Months
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Change in NYHA Functional Class
Tidsramme: Baseline to 6 Months, 6 months to 18 Months
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Change in New York Heart Association (NYHA) Functional Classification based on patient's self reported activity level. Worsened: documented increase in limitations of physical activity as self-described by subject Improved: documented decrease in limitations of physical activity as self-described by subject Unchanged: no documented change in limitations of physical activity as self-described by subject |
Baseline to 6 Months, 6 months to 18 Months
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Minnesota Living With Heart Failure Questionnaire Scores
Tidsramme: Assessed at 6 Months and 18 Months
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Minnesota Living with Heart Failure (MLHF) questionnaire has a total score from 0 to 105.
A higher score indicates that participants heart failure is preventing them from living their lives measured at two time points.
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Assessed at 6 Months and 18 Months
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Incidence of Major Adverse Cardiac Events (MACE)
Tidsramme: 18 Months
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Incidence of Major Adverse Cardiac Events (MACE).
A composite incidence of (1) death, (2) hospitalization for heart failure, or (3) non-fatal recurrent Ml.
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18 Months
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Number of Participants With Abnormal 48-Hour Ambulatory ECG Recordings
Tidsramme: Assessed at 6 Months, 12 Months, and 18 Months
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Ambulatory ECG monitoring is the most widely employed technology for the evaluation of a patient with symptoms suggestive of cardiac arrhythmia or conduction abnormality. When the patient returns for follow up the 48- Hour Ambulatory monitor provides the data to the site staff to detect any abnormal recordings based upon standard ECG protocol. |
Assessed at 6 Months, 12 Months, and 18 Months
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Change in Pulmonary Function
Tidsramme: Baseline, 6 Months, 12 Months, 18 Months
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Change in Pulmonary Function from Baseline to 6 month, Baseline to 12 month, and Baseline to 18 month visits as measured by forced expiratory volume in 1 second (FEV1)
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Baseline, 6 Months, 12 Months, 18 Months
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Serial Troponin Values (ng/mL)
Tidsramme: Assessed at Baseline, 12 hours, 24 hours, 36 hours, and 48 hours post CABG
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Serial Troponin Values (ng/mL) Values from Baseline to 48 Hours Post CABG
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Assessed at Baseline, 12 hours, 24 hours, 36 hours, and 48 hours post CABG
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Creatinine Kinase - Muscle/Brain (MB) (ng/mL)
Tidsramme: Assessed at Baseline, 12 Hours, 24 Hours, 36 Hours, and 48 hours post CABG
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Creatinine Kinase MB (ng/mL) Values every 12 hours from Baseline to 48 Hours Post CABG
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Assessed at Baseline, 12 Hours, 24 Hours, 36 Hours, and 48 hours post CABG
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Number of Clinically Significant Laboratory Values
Tidsramme: 18 Months
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Clinically significant laboratory values are first determined via standard laboratory normal values from a CAP and CLIA certified Laboratory and then assessed by investigator based on specific patient conditions and disease state.
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18 Months
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Rate of Treatment Emergent Adverse Events
Tidsramme: Assessed at 6 Months, 12 Months, and 18 Months
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Rate of Treatment Emergent Adverse Events Post Coronary Artery Bypass Graft (CABG) at 6 Months, 12 Months, and 18 Months
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Assessed at 6 Months, 12 Months, and 18 Months
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Number of Abnormal Echocardiogram Readings 2 Days Post CABG.
Tidsramme: Day 2
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The number of abnormal Echocardiogram readings 2 Days Post CABG will be documented based on transthoracic Echocardiographic standards.
However, although Echocardiograms 2 days post CABG operation may show abnormalities which is standard in this population, this testing is instrumental because it measures End- diastolic wall thickness and Left ventricular volumes at end-diastole and end-systole.
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Day 2
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Samarbejdspartnere og efterforskere
Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.
Sponsor
Samarbejdspartnere
Efterforskere
- Ledende efterforsker: Joshua M. Hare, MD, University of Miami
- Ledende efterforsker: Gary Gerstenblith, MD, Johns Hopkins University
- Ledende efterforsker: John V. Conte, MD, Johns Hopkins University
- Ledende efterforsker: Steven P. Schulman, MD, Johns Hopkins University
Publikationer og nyttige links
Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.
Datoer for undersøgelser
Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.
Studer store datoer
Studiestart
1. november 2007
Primær færdiggørelse (Faktiske)
1. juni 2011
Studieafslutning (Faktiske)
1. juni 2011
Datoer for studieregistrering
Først indsendt
2. januar 2008
Først indsendt, der opfyldte QC-kriterier
3. januar 2008
Først opslået (Skøn)
8. januar 2008
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
10. september 2019
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
19. august 2019
Sidst verificeret
1. august 2019
Mere information
Begreber relateret til denne undersøgelse
Yderligere relevante MeSH-vilkår
Andre undersøgelses-id-numre
- 20070598
- U54HL081028 (U.S. NIH-bevilling/kontrakt)
Plan for individuelle deltagerdata (IPD)
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