MSCs for Prevention of MI-induced HF

NCT05043610 | Completed Phase 3 DMC

• 1 other identifier: IR.SUMS.REC.1400.409
• Study Type: interventional
• Target: 420
• Locations: 1 country
• Sites: 3

Brief Summary

Results from recent clinical trials on bone marrow mononuclear cell (BM-MNC) transplantation show that this intervention can help reduce the incidence of heart failure (HF) after acute myocardial infarction (AMI). However, no study has evaluated the effect of the transplantation of mesenchymal stem cells (MSCs) on a clinical endpoint such as HF. This single-blinded, randomized, multicenter trial aims to establish whether the intracoronary infusion of umbilical cord-derived Wharton's jelly MSCs (WJ-MSCs) helps prevent HF development after AMI. The study will enroll 240 patients 3 to 7 days following an AMI treated with primary percutaneous coronary intervention (PPCI). Only patients aged below 65 years with impaired LV function (LVEF \< 40%) will be included. Patients will be randomized to receive either a single intracoronary infusion of WJ-MSCs or standard care. The primary outcome of this study is the assessment of HF development during long-term follow-up (three years). Since the efficacy of MSCs is higher than BM-MNCs after AMI in the improvement of LVEF, it would be probable that these cells may have a better clinical effect as well. However, no study has evaluated the impact of the transplantation of MSCs on a clinical endpoint such as HF. This study will help determine whether or not the infusion of intracoronary WJ-MSCs in AMI patients with impaired LVEF would prevent HF development and future adverse events.

Conditions

Myocardial Infarction, Acute; Myocardial Infarction First; Myocardial Infarction, Anterior Wall; Cardiac Remodeling, Ventricular; STEMI; Regenerative Medicine; Heart Failure

Keywords

WJ-MSCs; Myocardial infarction; Heart failure; Regenerative medicine; Tissue therapy; Stem cell therapy

Outcome Measures

Primary Outcomes (1)

• Incidence of Heart Failure

  The incidence of heart failure during the follow-up period.

  Checked at three years

Secondary Outcomes (3)

• Change in Left Ventricular Function from base line

  At baseline and after six months

• Cardiovascular Death

  Checked at three years

• Composite outcome of cardiovascular death and heart failure incidence

  Checked at three years

Study Arms (2)

WJ-MSCs intracoronary infusion + standard care

EXPERIMENTAL

In the experimental group, 3-7 days after an acute anterior myocardial infarction treated successfully with primary percutaneous coronary intervention, 120 patients will receive a single intracoronary infusion of 10\^7 umbilical cord-derived Wharton's Jelly Mesenchymal Stem Cells (WJ-MSCs) alongside conventional treatment.

Biological: Umbilical Cord-Derived Wharton's Jelly Mesenchymal Stem Cells (WJ-MSCs); Other: Conventional Treatment

standard care (Control Group)

ACTIVE COMPARATOR

In the control group, after an acute anterior myocardial infarction treated successfully with primary percutaneous coronary intervention, 240 patients will receive only conventional treatment.

Other: Conventional Treatment

Interventions

Umbilical Cord-Derived Wharton's Jelly Mesenchymal Stem Cells (WJ-MSCs) BIOLOGICAL

cGMP grade WJ-MSCs. 10\^7 WJ-MSCs will be delivered through the intracoronary route. WJ-MSCs will be infused at a rate of 2.5 ml/min across three portions.

WJ-MSCs intracoronary infusion + standard care

Conventional Treatment OTHER

Beta-blocker, angiotensin-converting enzyme (ACE) inhibitor, aldosterone antagonist, aspirin, ticagrelor, statin, and glyceryl trinitrate plus cardiac rehabilitation.

WJ-MSCs intracoronary infusion + standard care; standard care (Control Group)

Eligibility Criteria

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

You may qualify if:

• Age 18-65 years
• Either gender
• First myocardial infarction in the preceding 3 to 7 days
• Post-acute myocardial infarction left ventricular ejection fraction \< 40%
• Negative pregnancy test (for women of reproductive age)
• Written informed consent

You may not qualify if:

• A history of any prior cardiac conditions (valvular, ischemic, or congenital disorders)
• Regional wall motion abnormalities outside the region of the infarction
• LV dysfunction due to other etiologies like non-ischemic cardiomyopathy, anthracycline use, or ethanol abuse (\> 6 oz./day regularly)
• Poor echocardiography window
• Active infection, malignancy, or autoimmune disease

Sponsors & Collaborators

• Shiraz University of Medical Sciences: lead
• National Institute of Medical Research Development (NIMAD), Iran: collaborator

Study Sites (3)

Al-Zahra Heart Hospital, Shiraz University of Medical Sciences

Shiraz, Fars, Iran

Location

Faghihi Hospital

Shiraz, Fars, Iran

Location

Namazee Hospital

Shiraz, Fars, Iran

Location

Related Publications (13)

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  PMID: 35927674 BACKGROUND

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  PMID: 18955667 BACKGROUND

• Hellermann JP, Jacobsen SJ, Gersh BJ, Rodeheffer RJ, Reeder GS, Roger VL. Heart failure after myocardial infarction: a review. Am J Med. 2002 Sep;113(4):324-30. doi: 10.1016/s0002-9343(02)01185-3.

  PMID: 12361819 BACKGROUND

• Lewis EF, Moye LA, Rouleau JL, Sacks FM, Arnold JM, Warnica JW, Flaker GC, Braunwald E, Pfeffer MA; CARE Study. Predictors of late development of heart failure in stable survivors of myocardial infarction: the CARE study. J Am Coll Cardiol. 2003 Oct 15;42(8):1446-53. doi: 10.1016/s0735-1097(03)01057-x.

  PMID: 14563590 BACKGROUND

• Juilliere Y, Cambou JP, Bataille V, Mulak G, Galinier M, Gibelin P, Benamer H, Bouvaist H, Meneveau N, Tabone X, Simon T, Danchin N; FAST-MI Investigators. Heart failure in acute myocardial infarction: a comparison between patients with or without heart failure criteria from the FAST-MI registry. Rev Esp Cardiol (Engl Ed). 2012 Apr;65(4):326-33. doi: 10.1016/j.recesp.2011.10.027. Epub 2012 Feb 20.

  PMID: 22357361 BACKGROUND

• Braunwald E. Cell-Based Therapy in Cardiac Regeneration: An Overview. Circ Res. 2018 Jul 6;123(2):132-137. doi: 10.1161/CIRCRESAHA.118.313484. No abstract available.

  PMID: 29976683 BACKGROUND

• Taylor DA, Atkins BZ, Hungspreugs P, Jones TR, Reedy MC, Hutcheson KA, Glower DD, Kraus WE. Regenerating functional myocardium: improved performance after skeletal myoblast transplantation. Nat Med. 1998 Aug;4(8):929-33. doi: 10.1038/nm0898-929.

  PMID: 9701245 BACKGROUND

• Kocher AA, Schuster MD, Szabolcs MJ, Takuma S, Burkhoff D, Wang J, Homma S, Edwards NM, Itescu S. Neovascularization of ischemic myocardium by human bone-marrow-derived angioblasts prevents cardiomyocyte apoptosis, reduces remodeling and improves cardiac function. Nat Med. 2001 Apr;7(4):430-6. doi: 10.1038/86498.

  PMID: 11283669 BACKGROUND

• Williams AR, Hare JM. Mesenchymal stem cells: biology, pathophysiology, translational findings, and therapeutic implications for cardiac disease. Circ Res. 2011 Sep 30;109(8):923-40. doi: 10.1161/CIRCRESAHA.111.243147.

  PMID: 21960725 BACKGROUND

• Houtgraaf JH, den Dekker WK, van Dalen BM, Springeling T, de Jong R, van Geuns RJ, Geleijnse ML, Fernandez-Aviles F, Zijlsta F, Serruys PW, Duckers HJ. First experience in humans using adipose tissue-derived regenerative cells in the treatment of patients with ST-segment elevation myocardial infarction. J Am Coll Cardiol. 2012 Jan 31;59(5):539-40. doi: 10.1016/j.jacc.2011.09.065. No abstract available.

  PMID: 22281257 BACKGROUND

• Jeong H, Yim HW, Park HJ, Cho Y, Hong H, Kim NJ, Oh IH. Mesenchymal Stem Cell Therapy for Ischemic Heart Disease: Systematic Review and Meta-analysis. Int J Stem Cells. 2018 May 30;11(1):1-12. doi: 10.15283/ijsc17061.

  PMID: 29482311 BACKGROUND

• Gao LR, Chen Y, Zhang NK, Yang XL, Liu HL, Wang ZG, Yan XY, Wang Y, Zhu ZM, Li TC, Wang LH, Chen HY, Chen YD, Huang CL, Qu P, Yao C, Wang B, Chen GH, Wang ZM, Xu ZY, Bai J, Lu D, Shen YH, Guo F, Liu MY, Yang Y, Ding YC, Yang Y, Tian HT, Ding QA, Li LN, Yang XC, Hu X. Intracoronary infusion of Wharton's jelly-derived mesenchymal stem cells in acute myocardial infarction: double-blind, randomized controlled trial. BMC Med. 2015 Jul 10;13:162. doi: 10.1186/s12916-015-0399-z.

  PMID: 26162993 BACKGROUND

• Attar A, Mirhosseini SA, Mathur A, Dowlut S, Monabati A, Kasaei M, Abtahi F, Kiwan Y, Vosough M, Azarpira N. Prevention of acute myocardial infarction induced heart failure by intracoronary infusion of mesenchymal stem cells: phase 3 randomised clinical trial (PREVENT-TAHA8). BMJ. 2025 Oct 29;391:e083382. doi: 10.1136/bmj-2024-083382.

  PMID: 41224473 DERIVED

MeSH Terms

Conditions

Myocardial Infarction; Anterior Wall Myocardial Infarction; Ventricular Remodeling; ST Elevation Myocardial Infarction; Heart Failure

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis; Pathological Conditions, Anatomical

Study Officials

• Armin Attar, MD

  Department of Cardiovascular Medicine, TAHA clinical trial group, Shiraz University of Medical Sciences, Shiraz, Iran

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Single-blinded
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of cardiovascular regeneration and genetics program, and cardiovascular diseases' registries, Principal Investigator, Clinical Professor

Model Details: A single-blinded, randomized, multicenter trial.

Study Record Dates

• First Submitted: August 29, 2021
• First Posted: September 14, 2021
• Study Start: September 15, 2021
• Primary Completion: November 1, 2024
• Study Completion: November 1, 2024
• Last Updated: November 4, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: The study protocol is published.
• Access Criteria: Supporting data will be made available upon reasonable request. All inquiries should be sent to the study director, Dr. Armin Attar.

Locations

IR (3)