Bone Marrow Derived Adult Stem Cells for Acute Anterior Myocardial Infarction (REGEN-AMI)

• ClinicalTrials.gov Identifier: NCT00765453
• Recruitment Status: Completed
• First Posted: October 3, 2008
• Last Update Posted: March 2, 2020
• Sponsor: Barts & The London NHS Trust
• Collaborators: University College, London; Queen Mary University of London
• Information provided by (Responsible Party): Anthony Mathur, Barts & The London NHS Trust

Tracking Information

• First Submitted Date: October 2, 2008
• First Posted Date: October 3, 2008
• Last Update Posted Date: March 2, 2020
• Study Start Date: March 2008
• Actual Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: July 10, 2013): Longitudinal change in left ventricular function (ejection fraction) [ Time Frame: 1 year ]
• Original Primary Outcome Measures (submitted: October 2, 2008): Longitudinal change in left ventricular function (ejection fraction) as measured by cardiac MRI. [ Time Frame: 1 year ]

Current Secondary Outcome Measures (submitted: February 27, 2020)

• Longitudinal change in left ventricular function (ejection fraction), change in left ventricular end systolic volume, and change in infarct size [ Time Frame: 3 months ]
• Longitudinal change in left ventricular function as measured by LV angiography [ Time Frame: 6 months ]
• Longitudinal change in left ventricular function assessed by echocardiography. [ Time Frame: 6 months ]
• Change in left ventricular end systolic volume and change in infarct size. [ Time Frame: 12 months ]
• Longitudinal change in left ventricular function assessed by echocardiography. [ Time Frame: 12 months ]
• MACE [ Time Frame: 12 months ]
• Change in Quality of life [ Time Frame: 6 and 12 months ]

Original Secondary Outcome Measures (submitted: October 2, 2008)

• Longitudinal change in left ventricular function (ejection fraction) Reduction of left ventricular end systolic volume, Change in regional wall motion in infarct area and Change in infarct mass as measured by cardiac MRI [ Time Frame: 3 months ]
• Change in global ejection fraction as measured by LV angiography and improvement of myocardial contractility, assessed by contrast echocardiogram(wall motion score index). [ Time Frame: 6 months ]
• Major adverse cardiac events (MACE), Death (independent of cause and sudden death), myocardial infarction (Q-wave and Non-Q-wave), coronary revascularization [coronary bypass or PCI). [ Time Frame: 6 months ]
• Quality of life [ Time Frame: 6 months ]
• LV function as measured by cardiac MRI [ Time Frame: 12 months ]
• MACE [ Time Frame: 12 months ]
• Quality of life [ Time Frame: 12 months ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Bone Marrow Derived Adult Stem Cells for Acute Anterior Myocardial Infarction
• Official Title: Randomised Controlled Clinical Trial of the Use of Autologous Bone Marrow Derived Progenitor Cells to Salvage Myocardium in Patients With Acute Anterior Myocardial Infarction

Brief Summary

Study hypothesis :

The purpose of this study is to determine whether Intracoronary infusion of autologous bone marrow derived progenitor cells to patients undergoing primary angioplasty for acute anterior myocardial infarction will lead to an improvement in cardiac function greater than that seen by placebo alone.

Aims

• To demonstrate that it is safe and feasible to deliver autologous bone marrow derived stem cells within hours of the primary angioplasty procedure
• To demonstrate the effects of autologous bone marrow derived stem cells on cardiac function using cardiac MRI (or cardiac CT), echocardiography and left ventriculography.
• To demonstrate the effect of autologous bone marrow derived stem cells in addition to standard care leads to improvement in cardiac function compared to patients saline(placebo) and standard care.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Treatment
• Condition: Acute Myocardial Infarction

Intervention

• Other: Bone marrow derived progenitor cells or placebo infusion
  Over-the-wire balloon catheter delivers infusion into coronary vessel using a stop-flow technique
• Other: Placebo infusion
  Placebo infusion

Study Arms

• Experimental: Intracoronary
  Patients will be randomised in a 1:1 ratio to receive intracoronary injections of bone marrow derived stem/progenitor cells or placebo infusion through a percutaneous route
  Intervention: Other: Bone marrow derived progenitor cells or placebo infusion
• Placebo Comparator: Placebo
  Placebo infusion
  Intervention: Other: Placebo infusion

Publications *

• Choudry F, Hamshere S, Saunders N, Veerapen J, Bavnbek K, Knight C, Pellerin D, Locca D, Westwood M, Rakhit R, Crake T, Kastrup J, Parmar M, Agrawal S, Jones D, Martin J, Mathur A. A randomized double-blind control study of early intra-coronary autologous bone marrow cell infusion in acute myocardial infarction: the REGENERATE-AMI clinical trialdagger. Eur Heart J. 2016 Jan 14;37(3):256-63. doi: 10.1093/eurheartj/ehv493. Epub 2015 Sep 23.
• Hamshere S, Choudhury T, Jones DA, Locca D, Mills P, Rothman M, Knight C, Parmar M, Agrawal S, Martin J, Mathur A. A randomised double-blind control study of early intracoronary autologous bone marrow cell infusion in acute myocardial infarction (REGENERATE-AMI). BMJ Open. 2014 Feb 18;4(2):e004258. doi: 10.1136/bmjopen-2013-004258.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 10, 2013): 100
• Original Estimated Enrollment (submitted: October 2, 2008): 102
• Actual Study Completion Date: March 2018
• Actual Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Patients presenting to the Heart Attack Centre with acute anterior myocardial infarction (ST elevation in at least 2 contiguous anterior leads ≥ 0.2 mV) and treated with acute PCI with stent implantation within 24 hours after symptom onset
• Acute PCI / stent implantation has been successful (residual stenosis visually < 30% and TIMI flow ≥ 2).
• At the time of inclusion patient no longer requires i.v. catecholamines or mechanical hemodynamic support (aortic balloon pump)
• Significant regional wall motion abnormality in LV angiogram at the time of acute PCI in the LAD territory
• Age 18 - 80 Years (primary angioplasty confers an adverse prognosis in those over the age of 80 years)
• Written informed consent in the recruiting centres native language

Exclusion Criteria:

• Regional wall motion abnormality outside the area involved in the index acute myocardial infarction
• Need to revascularise additional vessels, outside the infarct artery as a planned procedure (these vessels can be treated at baseline)
• Arteriovenous malformations or aneurysms
• Active infection, or fever or diarrhoea within last 4 weeks
• Chronic inflammatory disease
• Known HIV infection or active hepatitis
• Neoplastic disease without documented remission within the past 5 years
• Cerebrovascular insult within 3 months
• Impaired renal function (creatinine > 200mmol) at the time of cell therapy
• Significant liver disease (GOT > 2x upper limit) or spontaneous INR > 1,5)
• Anemia (hemoglobin < 8.5 mg/dl)
• Platelet count < 100.000/µl
• Hypersplenism
• Known allergy or intolerance to clopidogrel, heparin or abciximab
• History of bleeding disorder
• Gastrointestinal bleeding within 3 months
• Major surgical procedure or trauma within 2 months
• Uncontrolled hypertension
• Pregnancy
• Mental retardation leading to inability to obtain informed consent
• Previously performed stem / progenitor cell therapy
• Participation in another clinical trial within the last 30 days

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Denmark, Switzerland, United Kingdom

Administrative Information

• NCT Number: NCT00765453
• Other Study ID Numbers: 07/Q0603/76; 2007-002-144
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Anthony Mathur, Barts & The London NHS Trust
• Original Responsible Party: Anthony Mathur, Barts & The London NHS Trust
• Current Study Sponsor: Barts & The London NHS Trust
• Original Study Sponsor: Same as current

Collaborators

• University College, London
• Queen Mary University of London

Investigators

• Principal Investigator: Anthony Mathur, FRCP FESC Ph; Barts and the London NHS Trust

• PRS Account: Barts & The London NHS Trust
• Verification Date: February 2020