- ICH GCP
- Amerikanska kliniska prövningsregistret
- Klinisk prövning NCT00300053
ACT34-CMI -- Adult Autologous CD34+ Cells
8 januari 2021 uppdaterad av: Lisata Therapeutics, Inc.
A DB, Randomized, Placebo-controlled Study of the Tolerability, Efficacy, Safety, and Dose Range of Intramyocardial CLBS14 for Reduction of Angina Episodes in Patients With Refractory Chronic Myocardial Ischemia (ACT34-CMI)
The purpose of this study is to evaluate the efficacy and safety of intramyocardial injections of CLBS14 in patients with refractory chronic myocardial ischemia.
Studieöversikt
Status
Avslutad
Betingelser
Intervention / Behandling
Detaljerad beskrivning
This is a double-blind, prospective, randomized, placebo-controlled trial to determine the tolerability, efficacy, safety and dose range of intramyocardial injections of adult autologous CD34+ cells mobilized with granulocyte colony stimulating factor (G-CSF) for the reduction of angina episodes in patients with refractory chronic myocardial ischemia.
Studietyp
Interventionell
Inskrivning (Faktisk)
321
Fas
- Fas 2
Kontakter och platser
Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.
Studieorter
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Alabama
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Birmingham, Alabama, Förenta staterna, 35211
- Cardiology PC
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Arizona
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Phoenix, Arizona, Förenta staterna, 85054
- Mayo Clinic Hospital
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Phoenix, Arizona, Förenta staterna, 85005
- Arizona Heart Institute
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California
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La Jolla, California, Förenta staterna, 92037
- Scripps Memorial Hospital
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Stanford, California, Förenta staterna, 94305
- Stanford University Hospital and Clinics
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District of Columbia
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Washington, District of Columbia, Förenta staterna, 20010
- Washington Hospital Center
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Florida
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Fort Lauderdale, Florida, Förenta staterna, 33308
- Holy Cross Hospital
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Gainesville, Florida, Förenta staterna, 32610
- University of Florida Health Science Center
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Jacksonville, Florida, Förenta staterna, 32209
- University of Florida Health Science Center
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Orlando, Florida, Förenta staterna, 32803
- Central Florida Cardiology Group
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Georgia
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Atlanta, Georgia, Förenta staterna, 30342
- Saint Joseph's Research Institute
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Illinois
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Chicago, Illinois, Förenta staterna, 60612
- Rush University Medical Center
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Chicago, Illinois, Förenta staterna, 60611
- Northwestern University Medical Center, Bluhm Cardiovascluar Institute
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Iowa
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Iowa City, Iowa, Förenta staterna, 52242
- University of Iowa Hospitals & Clinic
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Massachusetts
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Boston, Massachusetts, Förenta staterna, 02114
- Massachusetts General Hospital
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Boston, Massachusetts, Förenta staterna, 02135
- Caritas Saint Elizabeth's Medical Center
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Minnesota
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Minneapolis, Minnesota, Förenta staterna, 55407
- Abbott Northwestern Hospital
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New York
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New York, New York, Förenta staterna, 10032
- New York Presbyterian Hospital - Columbia University Medical Center
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New York, New York, Förenta staterna, 10065
- New York Presbyterian Hospital - Weill Cornell Medical College of Cornell University
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Ohio
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Cincinnati, Ohio, Förenta staterna, 45267
- University of Cincinnati Medical Center
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Cincinnati, Ohio, Förenta staterna, 45219
- The Lindner Clinical Trial Center
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Cleveland, Ohio, Förenta staterna, 44106
- University Hospitals Case Medical Center
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Pennsylvania
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Pittsburgh, Pennsylvania, Förenta staterna, 15213
- University of Pittsburgh Medical Center
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Washington
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Seattle, Washington, Förenta staterna, 98122
- Swedish Heart & Vascular - Swedish Medical Center
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Wisconsin
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Madison, Wisconsin, Förenta staterna, 53792
- University of Wisconsin Medical School
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Milwaukee, Wisconsin, Förenta staterna, 53223
- Comprehensive Cardiovascular Care Group
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Deltagandekriterier
Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.
Urvalskriterier
Åldrar som är berättigade till studier
21 år till 80 år (Vuxen, Äldre vuxen)
Tar emot friska volontärer
Nej
Kön som är behöriga för studier
Allt
Beskrivning
Inclusion Criteria:
- Canadian Cardiovascular Society (CCS) functional class III or IV chronic refractory angina
- subjects without control of their angina symptoms, in spite of maximal tolerated doses of anti-anginal drugs, must be on optimal therapy for their angina and on a stable anti-anginal medication regimen for at least 1 month prior to entering the screening period of the study
- identified as unsuitable for conventional revascularization
- recent coronary angiogram (within the last 12 months) to document the coronary anatomy and to verify the revascularization procedures
- subjects must have objective evidence of inducible ischemia or viable myocardium in the potential target injection zone
- a left ventricular ejection fraction equal to or greater than 25% by ECHO or single photon emission computed tomography (SPECT) at screening
- subjects must experience at minimum an average of 7 angina or anginal equivalent episodes per week
- subjects must be able to complete a minimum of 3 minutes but nor more than 10 minutes on a treadmill following the Modified Bruce Protocol
- subjects must experience angina or anginal equivalent episodes during the screening exercise treadmill test
- female subjects must either be no longer capable of reproduction or using medically valid contraception to prevent pregnancy during the study
- subjects must be willing and able to comply with specified follow-up evaluations
Exclusion Criteria:
- predominant congestive heart failure
- myocardial infarction within 60 days of treatment
- successful or partially successful coronary revascularization procedures (any vessel) within 6 months of study enrollment
- placement of a bi-ventricular pacemaker for cardiac resynchronization therapy (CRT) for heart failure in the past 90 days
- documented stroke or transient ischemic attack (TIA) within 60 days of study enrollment
- history of moderate to severe aortic stenosis or severe aortic insufficiency; severe mitral stenosis or severe mitral insufficiency
- prosthetic aortic valve replacement
- evidence of any life-threatening arrhythmia that requires intervention on the 24-hour Holter monitor. Life-threatening arrhythmia that is successfully treated with an implantable cardioverter defibrillator (ICD) is not exclusionary.
- splenomegaly and/or severe co-morbidity associated with a reduction in life expectancy of less than 1 year, such as chronic medical illness (ie, severe chronic obstructive pulmonary disease, renal failure or cancer [exceptions: in-situ skin cancer or fully removed skin cancer other than melanoma, in-situ cervical cancer, or cancer free for 5 years with no history of a stem cell transplant])
- sickle cell disease or sickle cell trait
- platelet count greater than 10% above the upper limit of normal or a platelet count below 100,000 if on Clopidogrel or 50,000 without Clopidogrel
- hematocrit <30%
- serum creatinine >2.5 mg/dL
- any clinically significant laboratory abnormality on screening laboratories
- currently enrolled in another IDE or IND that has not completed the protocol required primary follow-up period (excludes 15 year follow up of gene therapy trials)
- history of alcohol or drug abuse within 3 months of screening
- joint or peripheral vascular disease or neurologic disease that severely limits treadmill walking
- chronic obstructive pulmonary disease that severely limits walking or FEV1 <30% predicted
- females who are pregnant or lactating
- female subjects who are capable of reproduction and will not use medically valid contraception to prevent pregnancy during the study
- subjects who test positive for HIV, hepatitis B or hepatitis C, or are on chronic immunosuppressive medications or have had a prior stem cell transplant
- subjects with a known hypersensitivity to E. coli-derived proteins, or to any component of Neupogen (Filgrastim) or G-CSF
- subjects who have a significant psychiatric disorder or mental disability that could interfere with the subject´s ability to provide informed consent and/or comply with protocol procedures
Studieplan
Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.
Hur är studien utformad?
Designdetaljer
- Primärt syfte: Behandling
- Tilldelning: Randomiserad
- Interventionsmodell: Parallellt uppdrag
- Maskning: Trippel
Vapen och interventioner
Deltagargrupp / Arm |
Intervention / Behandling |
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Experimentell: CLBS14: Low-Dose Group
10 intramyocardial injections of 0.2 mL each of auto-CD34+ cells at a dose of 1 x 10^5 (=100000) cells/kg bodyweight
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Eligible subjects will receive subcutaneous injections of 5 µg/kg/day G-CSF for 5 days to mobilize CD34+ cells from the bone marrow to the peripheral blood.
Mononuclear cells (MNCs) will be collected via apheresis on day 5. On the day of the cell/placebo injection (day 6), the apheresis product will be enriched for CD34+ cells using the Isolex 300i Magnetic Cell Selection System (Baxter Healthcare).
Autologous CD34+ cells will be delivered in 10 intramyocardial injections of 0.2 mL at a dose of 1 x 10^5 (=100000) cells/kg bodyweight each using the MyoStar injection catheter (Biosense Webster, Inc.) into the target areas of myocardial ischemia.
Andra namn:
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Experimentell: CLBS14: High-Dose Group
10 intramyocardial injections of 0.2 mL each of auto-CD34+ cells at a dose of 5 x 10^5 (=500000) cells/kg bodyweight
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Eligible subjects will receive subcutaneous injections of 5 µg/kg/day G-CSF for 5 days to mobilize CD34+cells from the bone marrow to the peripheral blood.
Mononuclear cells (MNCs) will be collected via apheresis on day 5. On the day of the cell/placebo injection (day 6), the apheresis product will be enriched for CD34+ cells using the Isolex 300i Magnetic Cell Selection System (Baxter Healthcare).
Autologous CD34+ cells will be delivered in 10 intramyocardial injections of 0.2 mL at a dose of 5 x 10^5 (=500000) cells/kg bodyweight each using the MyoStar injection catheter (Biosense Webster, Inc.) into the target areas of myocardial ischemia.
Andra namn:
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Placebo-jämförare: Placebo injection
10 intramyocardial injections of 0.2 mL each of 0.9% NaCl (saline) in 5% autologous plasma
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Eligible subjects will receive subcutaneous injections of 5 µg/kg/day G-CSF for 5 days to mobilize CD34+ cells from the bone marrow to the peripheral blood.
Mononuclear cells (MNCs) will be collected via apheresis on day 5. On the day of the cell/placebo injection (day 6), the apheresis product will be enriched for CD34+ cells using the Isolex 300i Magnetic Cell Selection System (Baxter Healthcare).
Placebo will be delivered in 10 intramyocardial injections of 0.2 mL each of 0.9% NaCl (saline) in 5% autologous plasma into the target areas of myocardial ischemia.
Andra namn:
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Vad mäter studien?
Primära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
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Number of Angina Episodes Per Week at 6 and 12 Months
Tidsram: 6 and 12 months
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The number of angina episodes were collected via an electronic subject diary for four weeks at Baseline and at 6 and 12 months.
The four-week angina episodes (per week mean) were used as the frequency for each visit.
A lower number represents fewer angina episodes.
A lower number is better.
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6 and 12 months
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Sekundära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
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Exercise Treadmill Test According to Modified Bruce Protocol: Mean Change From Baseline in Duration of Exercise
Tidsram: Change from Baseline to 6 months and change from baseline to 12 months after treatment
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A modified Bruce Protocol Exercise Treadmill Test was used to evaluate duration of exercise in all subjects.
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Change from Baseline to 6 months and change from baseline to 12 months after treatment
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Number of Participants With Change in Canadian Cardiovascular Society Anginal Classification Levels
Tidsram: Baseline and 12 months after treatment
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The Canadian Cardiovascular Society (CCS) Functional Classification of Angina is as follows:
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Baseline and 12 months after treatment
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Changes From Baseline in Seattle Angina Questionnaire (SAQ) Scores at 6 Months
Tidsram: Baseline to 6 months after treatment
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Angina symptoms were evaluated based on the Seattle Angina Questionnaire (SAQ), which was used to analyze the following: physical limitations, angina stability, angina frequency, treatment satisfaction, and disease perception.
The SAQ consisted of 11 questions with 5 or 6 possible responses.
Responses were ordinal values (1-7, 10, 11, 97, depending on the type of question; no uniform ranges throughout); responses that corresponded to the lowest level of functioning (worse outcomes) were assigned values of 1, while responses that corresponded to higher functioning levels (better outcome) were assigned a higher ordinal value.
If the response to any of these questions was 97 it was recoded as a missing value.
Each scale can have a scored value ranging from 0 to 100.
A larger number is better.
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Baseline to 6 months after treatment
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Changes From Baseline to 6 Months in Short Form 36 (SF-36) Parameters
Tidsram: Baseline to 6 months after treatment
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The Short Form 36 (SF-36) health survey form was used to analyze physical functioning, role limitations due to physical health, bodily pain, general health perceptions, vitality, social functioning, role limitations due to emotional problems, general mental health, and health transition.
Responses were coded as ordinal numbers going from worst (=1) to best (=highest number).
These ordinal scores were transformed into scales ranging from 0 to 100.
Higher numbers are generally considered better.
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Baseline to 6 months after treatment
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Change in Anti-anginal Medication (ie, Nitroglycerin) Use
Tidsram: Baseline to 6 months
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The mean nitroglycerin use per week was analyzed at baseline and 6 months
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Baseline to 6 months
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Samarbetspartners och utredare
Det är här du hittar personer och organisationer som är involverade i denna studie.
Sponsor
Utredare
- Studierektor: Caladrius Study DIrector, Lisata Therapeutics, Inc.
Publikationer och användbara länkar
Den som ansvarar för att lägga in information om studien tillhandahåller frivilligt dessa publikationer. Dessa kan handla om allt som har med studien att göra.
Allmänna publikationer
- Losordo DW, Henry TD, Davidson C, Sup Lee J, Costa MA, Bass T, Mendelsohn F, Fortuin FD, Pepine CJ, Traverse JH, Amrani D, Ewenstein BM, Riedel N, Story K, Barker K, Povsic TJ, Harrington RA, Schatz RA; ACT34-CMI Investigators. Intramyocardial, autologous CD34+ cell therapy for refractory angina. Circ Res. 2011 Aug 5;109(4):428-36. doi: 10.1161/CIRCRESAHA.111.245993. Epub 2011 Jul 7.
- Henry TD, Schaer GL, Traverse JH, Povsic TJ, Davidson C, Lee JS, Costa MA, Bass T, Mendelsohn F, Fortuin FD, Pepine CJ, Patel AN, Riedel N, Junge C, Hunt A, Kereiakes DJ, White C, Harrington RA, Schatz RA, Losordo DW; ACT. Autologous CD34+ Cell Therapy for Refractory Angina: 2-Year Outcomes From the ACT34-CMI Study. Cell Transplant. 2016;25(9):1701-1711. doi: 10.3727/096368916X691484. Epub 2016 May 4.
- Povsic TJ, Losordo DW, Story K, Junge CE, Schatz RA, Harrington RA, Henry TD. Incidence and clinical significance of cardiac biomarker elevation during stem cell mobilization, apheresis, and intramyocardial delivery: an analysis from ACT34-CMI. Am Heart J. 2012 Nov;164(5):689-697.e3. doi: 10.1016/j.ahj.2012.06.022.
Studieavstämningsdatum
Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.
Studera stora datum
Studiestart
1 april 2006
Primärt slutförande (Faktisk)
1 mars 2008
Avslutad studie (Faktisk)
1 mars 2009
Studieregistreringsdatum
Först inskickad
6 mars 2006
Först inskickad som uppfyllde QC-kriterierna
6 mars 2006
Första postat (Uppskatta)
8 mars 2006
Uppdateringar av studier
Senaste uppdatering publicerad (Faktisk)
26 januari 2021
Senaste inskickade uppdateringen som uppfyllde QC-kriterierna
8 januari 2021
Senast verifierad
1 januari 2021
Mer information
Termer relaterade till denna studie
Nyckelord
Ytterligare relevanta MeSH-villkor
Andra studie-ID-nummer
- 24779
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