Prospective Randomized Study of Mesenchymal Stem Cell Therapy in Patients Undergoing Cardiac Surgery (PROMETHEUS)

NCT00587990 | Terminated Phase 1 Results DMC FDA Drug

• 2 other identifiers: 20070598U54HL081028
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 2

Brief Summary

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).

Conditions

Stem Cell Transplantation; Ventricular Dysfunction, Left

Keywords

Chronic Ischemic Left Ventricular Dysfunction

Outcome Measures

Primary Outcomes (1)

• Number of Patients With Serious Adverse Events

  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.

  12 Months

Secondary Outcomes (18)

• Change in Infarct Scar Size (ISS) Over 18 Month Period

  Baseline, 6 Months, 18 Months

• Left Ventricular Function (LVF) in Region of MSC Injection

  Assessed at Baseline and 18 Months

• Regional Left Ventricular Wall Thickening

  Assessed at Baseline and 18 months

• Left Ventricular End Diastolic Wall Thickness

  Assessed at Baseline and 18 months

• Change in Left Ventricular End Diastolic and Systolic Volume

  Baseline, 6 Months, 18 Months

Study Arms (3)

Lower dose mesenchymal stem cell (MSC) injection

EXPERIMENTAL

Participants will receive lower dose mesenchymal stem cell injections for a total of 2 x 10\^7 cells

Biological: Lower dose mesenchymal stem cell (MSC) injection

Higher dose MSC injection

EXPERIMENTAL

Participants will receive higher dose of mesenchymal stem cell injections for a total of 2 x 10\^8 cells

Biological: Higher dose MSC injection

(3) Placebo

PLACEBO COMPARATOR

Participants will receive placebo injections

Genetic: Placebo

Interventions

Lower dose mesenchymal stem cell (MSC) injection BIOLOGICAL

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.

Lower dose mesenchymal stem cell (MSC) injection

Placebo GENETIC

Participants will receive between 10 and 20 placebo injections that consist of phosphate buffered saline (PBS) and 1% human serum albumin (HSA).

(3) Placebo

Higher dose MSC injection BIOLOGICAL

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.

Higher dose MSC injection

Eligibility Criteria

• Age: 21 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Joshua M Hare: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• Johns Hopkins University Specialized Center for Cell Based Therapy: collaborator
• The Emmes Company, LLC: collaborator

Study Sites (2)

University of Miami Miller School of Medicine

Miami, Florida, 33136, United States

Location

Johns Hopkins University School of Medicine

Baltimore, Maryland, 21205, United States

Location

Related Publications (1)

• Karantalis V, DiFede DL, Gerstenblith G, Pham S, Symes J, Zambrano JP, Fishman J, Pattany P, McNiece I, Conte J, Schulman S, Wu K, Shah A, Breton E, Davis-Sproul J, Schwarz R, Feigenbaum G, Mushtaq M, Suncion VY, Lardo AC, Borrello I, Mendizabal A, Karas TZ, Byrnes J, Lowery M, Heldman AW, Hare JM. Autologous mesenchymal stem cells produce concordant improvements in regional function, tissue perfusion, and fibrotic burden when administered to patients undergoing coronary artery bypass grafting: The Prospective Randomized Study of Mesenchymal Stem Cell Therapy in Patients Undergoing Cardiac Surgery (PROMETHEUS) trial. Circ Res. 2014 Apr 11;114(8):1302-10. doi: 10.1161/CIRCRESAHA.114.303180. Epub 2014 Feb 24.

  PMID: 24565698 RESULT

MeSH Terms

Conditions

Ventricular Dysfunction, Left

Interventions

Injections

Condition Hierarchy (Ancestors)

Ventricular Dysfunction; Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics

Limitations and Caveats

Limitations due to slow enrollment and premature closure.

Results Point of Contact

• Title: Adam Mendizabal
• Organization: EMMES Corporation

amendizabal@emmes.com

301-251-1161

Study Officials

• Joshua M. Hare, MD

  University of Miami

  PRINCIPAL INVESTIGATOR

• Gary Gerstenblith, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

• John V. Conte, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

• Steven P. Schulman, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director, Interdisciplinary Stem Cell Institute

Study Record Dates

• First Submitted: January 2, 2008
• First Posted: January 8, 2008
• Study Start: November 1, 2007
• Primary Completion: June 1, 2011
• Study Completion: June 1, 2011
• Last Updated: September 10, 2019
• Results First Posted: April 2, 2015

Record last verified: 2019-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)