Document Detail


Effect of the use and timing of bone marrow mononuclear cell delivery on left ventricular function after acute myocardial infarction: the TIME randomized trial.
MedLine Citation:
PMID:  23129008     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
CONTEXT: While the delivery of cell therapy after ST-segment elevation myocardial infarction (STEMI) has been evaluated in previous clinical trials, the influence of the timing of cell delivery on the effect on left ventricular function has not been analyzed.
OBJECTIVES: To determine the effect of intracoronary autologous bone marrow mononuclear cell (BMC) delivery after STEMI on recovery of global and regional left ventricular function and whether timing of BMC delivery (3 days vs 7 days after reperfusion) influences this effect.
DESIGN, SETTING, AND PATIENTS: A randomized, 2 × 2 factorial, double-blind, placebo-controlled trial, Timing In Myocardial infarction Evaluation (TIME) enrolled 120 patients with left ventricular dysfunction (left ventricular ejection fraction [LVEF] ≤ 45%) after successful primary percutaneous coronary intervention (PCI) of anterior STEMI between July 17, 2008, and November 15, 2011, as part of the Cardiovascular Cell Therapy Research Network sponsored by the National Heart, Lung, and Blood Institute.
INTERVENTIONS: Intracoronary infusion of 150 × 106 BMCs or placebo (randomized 2:1) within 12 hours of aspiration and cell processing administered at day 3 or day 7 (randomized 1:1) after treatment with PCI.
MAIN OUTCOME MEASURES: The primary end points were change in global (LVEF) and regional (wall motion) left ventricular function in infarct and border zones at 6 months measured by cardiac magnetic resonance imaging and change in left ventricular function as affected by timing of treatment on day 3 vs day 7. The secondary end points included major adverse cardiovascular events as well as changes in left ventricular volumes and infarct size.
RESULTS: The mean (SD) patient age was 56.9 (10.9) years and 87.5% of participants were male. At 6 months, there was no significant increase in LVEF for the BMC group (45.2% [95% CI, 42.8% to 47.6%] to 48.3% [95% CI, 45.3% to 51.3%) vs the placebo group (44.5% [95% CI, 41.0% to 48.0%] to 47.8% [95% CI, 43.4% to 52.2%]) (P = .96). There was no significant treatment effect on regional left ventricular function observed in either infarct or border zones. There were no significant differences in change in global left ventricular function for patients treated at day 3 (−0.9% [95% CI, −6.6% to 4.9%], P = .76) or day 7 (1.1% [95% CI, −4.7% to 6.9%], P = .70). The timing of treatment had no significant effect on regional left ventricular function recovery. Major adverse events were rare among all treatment groups.
CONCLUSION: Among patients with STEMI treated with primary PCI, the administration of intracoronary BMCs at either 3 days or 7 days after the event had no significant effect on recovery of global or regional left ventricular function compared with placebo.
TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00684021.
Authors:
Jay H Traverse; Timothy D Henry; Carl J Pepine; James T Willerson; David X M Zhao; Stephen G Ellis; John R Forder; R David Anderson; Antonis K Hatzopoulos; Marc S Penn; Emerson C Perin; Jeffrey Chambers; Kenneth W Baran; Ganesh Raveendran; Charles Lambert; Amir Lerman; Daniel I Simon; Douglas E Vaughan; Dejian Lai; Adrian P Gee; Doris A Taylor; Christopher R Cogle; James D Thomas; Rachel E Olson; Sherry Bowman; Judy Francescon; Carrie Geither; Eileen Handberg; Casey Kappenman; Lynette Westbrook; Linda B Piller; Lara M Simpson; Sarah Baraniuk; Catalin Loghin; David Aguilar; Sara Richman; Claudia Zierold; Daniel B Spoon; Judy Bettencourt; Shelly L Sayre; Rachel W Vojvodic; Sonia I Skarlatos; David J Gordon; Ray F Ebert; Minjung Kwak; Lemuel A Moyé; Robert D Simari;
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Publication Detail:
Type:  Journal Article; Randomized Controlled Trial; Research Support, N.I.H., Intramural    
Journal Detail:
Title:  JAMA : the journal of the American Medical Association     Volume:  308     ISSN:  1538-3598     ISO Abbreviation:  JAMA     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-12-13     Completed Date:  2012-12-14     Revised Date:  2014-01-14    
Medline Journal Info:
Nlm Unique ID:  7501160     Medline TA:  JAMA     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2380-9     Citation Subset:  AIM; IM    
Data Bank Information
Bank Name/Acc. No.:
ClinicalTrials.gov/NCT00684021
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MeSH Terms
Descriptor/Qualifier:
Aged
Bone Marrow Transplantation / methods*
Double-Blind Method
Female
Humans
Magnetic Resonance Imaging
Male
Middle Aged
Myocardial Infarction / complications,  therapy*
Time Factors
Treatment Outcome
Ventricular Dysfunction, Left / complications,  therapy*
Grant Support
ID/Acronym/Agency:
5 U01 HL087318-04/HL/NHLBI NIH HHS; U01 HL087318/HL/NHLBI NIH HHS
Investigator
Investigator/Affiliation:
Sonia Skarlatos / ; David Gordon / ; Ray Ebert / ; Wendy Taddei-Peters / ; Min Jung Kwak / ; Beckie Chamberlin / ; Robert Simari / ; Timothy Henry / ; Jay Traverse / ; David McKenna / ; Beth Jorgenson / ; Rachel Olson / ; Stephen Ellis / ; Marc Penn / ; Saif Anwaruddin / ; James Harvey / ; Jane Reese Koc / ; Carrie Geither / ; Mark Jarosz / ; Cindy Oblak / ; James Willerson / ; Emerson Perin / ; Guilherme Silva / ; James Chen / ; Casey Kappenman / ; Deirdre Smith / ; Lynette Westbrook / ; Carl Pepine / ; Barry Byrne / ; David Anderson / ; John Wingard / ; Eileen Handberg / ; Tempa Curry / ; Diann Fisk / ; David Zhao / ; Antonis Hatzopoulos / ; Allen Naftilan / ; Sherry Bowman / ; Judy Francescon / ; Karen Prater / ; Ken Baran / ; Jody LaRock / ; Jeffrey Chambers / ; Betty Hargan / ; Ganesh Raveendran / ; Emily Caldwell / ; Barb Bruhn-Ding / ; Daniel Simon / ; Marco Costa / ; Stacey Mazzurco / ; Charles Lambert / ; Elizabeth Szymanski / ; Amir Lerman / ; Kelly Noonan / ; Biswajit Kar / ; Lemuel Moyé / ; Dejian Lai / ; Linda Piller / ; Lara Simpson / ; Sarah Baraniuk / ; Shreela Sharma / ; Judy Bettencourt / ; Shelly Sayre / ; Rachel Vojvodic / ; Larry Cormier / ; Robert Brown / ; Diane Eady / ; Kristen Lucas / ; Sibi Mathew / ; Michelle Cohen / ; Adrian Gee / ; Sara Richman / ; David Aguilar / ; Catalin Loghin / ; John Forder / ; Christopher R Cogle / ; Elizabeth Wise / ; James Thomas / ; Allen Borowski / ; Annitta Flinn / ; Cathy McDowell / ; Doris Taylor / ; Claudia Zierold / ; Marjorie Carlson /
Comments/Corrections
Comment In:
Nat Rev Cardiol. 2013 Jan;10(1):8   [PMID:  23165067 ]
JAMA. 2012 Dec 12;308(22):2405-6   [PMID:  23117584 ]
Erratum In:
JAMA. 2013 Jan 23;309(4):343

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