Rigor Reviewed

Rigor-Reviewed Manuscript

Prevention of acute myocardial infarction induced heart failure by intracoronary infusion of mesenchymal stem cells: phase 3 randomised clinical trial (PREVENT-TAHA8)

Name: Αlpha¹ Rigor Record — Prevention of acute myocardial infarction induced heart failure by intracoronary infusion of mesenchymal stem cells: phase 3 randomised clinical trial (PREVENT-TAHA8)
Item: Prevention of acute myocardial infarction induced heart failure by intracoronary infusion of mesenchymal stem cells: phase 3 randomised clinical trial (PREVENT-TAHA8)
Rating: 84
Author: Αlpha¹

Attar A, Mirhosseini SA, Mathur A, Dowlut S, Monabati A, Kasaei M, Abtahi F, Kiwan Y, Vosough M, Azarpira N.

Paper source

Read full text (PMC)Journal

Embed this Rigor badge

Αlpha¹ Rigor Review — 1.25★ (Critical), 0 critical, 8 high issues for “Prevention of acute myocardial infarction induced heart failure by intracoronary infusion of mesenchymal stem cells: phase 3 randomised clinical trial (PREVENT-TAHA8)”

Links back to this Rigor Record.

Αlpha¹ Editorial

This rigor review was examined and confirmed by Αlpha¹ Editorial · August 5, 2026

Αlpha¹ Rigor Review

Rigor Reviewed

1.25 / 5

Critical — a demonstrable failure

Interventional Study

Critical

High-priority

How this rating was calculated▸

Started at 5★ — deductions

IntegrityIntegrity concern ×5−2.5★
ClaimsUnsupported claim (uncorroborated)−0.5★
ReportingData & code availability not met−0.5★
ReportingStatistical analysis partially met−0.25★

Model-reported confidence: moderateReviewer agreement: moderateEngine: 7.15.0Source: full text

Problems surfaced6 types

Conclusions not supported by the paper’s own evidence
Data and code not shared
Statistical reporting gaps (tests, assumptions, effect sizes)
Internal contradictions in the reported numbers
Data look implausibly clean
Other integrity concern

This Αlpha¹ Rigor Review uses AI Rigor Reviewers trained on a curated corpus of high-fidelity and retracted papers, with expert supervision and curation. It can still make mistakes; verify each finding against the source before relying on it.

The paper reports a well-designed Phase 3 randomized trial with clear methods and transparent reporting. However, several arithmetic inconsistencies in key tables (incidence rates, hazard ratio) and a truncated data availability statement reduce the robustness of the published record. The missing details for the investigational product (manufacturer, antibody clones, mycoplasma testing) also limit reproducibility.

Eight dimensions evaluated, all applicable. The three independent reviewer runs converged on most dimensions; minor divergences on study design (power analysis adequacy), biological variables (demographics completeness), and key resources (product detail adequacy) were resolved by weighing the specific evidence. The statistics recomputation checked 18 tests and found all consistent, but the arithmetic errors in Table 2 and the HR inconsistency are not covered by that check.

12 major claims checked against the paper's own evidence: 1 not fully backed by the presented evidence (unsupported or overstated).

Efficacy claim is anchored to an adequate endpoint and a meaningful effect.

Recomputed 18 tests: 18 consistent, 0 inconsistent; 2 recomputed directly from the reported test statistics, 16 via agent-written checks.

5 integrity concerns flagged (0 high).

Reporting

Eight Dimensions6 pass · 1 warn · 1 fail

The introduction cites the BAMI trial's negative mortality result and points to heart-failure incidence as a more sensitive endpoint, references a prior phase 2 trial of the same cells, and a meta-analysis. Limitations of prior work are explicitly acknowledged (small samples, surrogate endpoints, short follow-up). The rationale logically links stem-cell biology and prior evidence to the trial's objectives.

Sub-criteria

prior work citedADEQUATE

premise rationaleADEQUATE

limitations addressedADEQUATE

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 95% conf

The study establishes a clear scientific foundation by citing prior trials (BAMI, REPAIR-AMI, a meta-analysis) and its own phase 2 work, and by justifying the choice of heart-failure incidence as a clinical endpoint.

Evidence

direct quote[Introduction]

“The BAMI trial, the largest phase 3 trial in this area, used total mortality as its primary endpoint but did not show a significant benefit, despite a significant reduction in hospital admissions for heart failure after intracoronary infusion of bone marrow derived mononuclear cells.”

direct quote[Introduction]

“These findings highlight the challenges of using mortality as a primary endpoint in cell therapy trials and suggest that incidence of heart failure may be a more appropriate and sensitive clinical outcome for evaluating efficacy.”

direct quote[Introduction]

“Our previous phase 2 trial showed the effectiveness of intracoronary infusion of Wharton’s jelly derived mesenchymal stem cells in improving left ventricular ejection fraction after myocardial infarction.”

PASSReviewer 2· 95% conf

The paper clearly establishes the scientific premise by citing prior research, providing a logical rationale, and addressing limitations of previous studies.

Evidence

direct quote[Introduction, paragraph 2]

“Despite growing interest, most clinical trials investigating stem cell therapy have been limited by small sample sizes and a focus on surrogate endpoints such as cardiac biomarkers, left ventricular ejection fraction, or scar size.”

direct quote[Introduction, paragraph 3]

“Mesenchymal stem cells have shown greater promise than bone marrow derived mononuclear cells for treating patients with acute myocardial infarction.”

paraphrase[Introduction, last paragraph]

“Building on these insights, we designed a phase 3 clinical trial with long term follow-up to assess the effect of intracoronary infusion of Wharton's jelly derived mesenchymal stem cells on the development of post-myocardial infarction heart failure.”

PASSReviewer 3· 95% conf

The introduction establishes a clear rationale from prior stem-cell trials (BAMI, REPAIR-AMI, meta-analyses) and explains how PREVENT-TAHA8 addresses their limitations (clinical endpoints, follow-up duration, sample size).

Evidence

direct quote[Introduction]

“most clinical trials investigating stem cell therapy have been limited by small sample sizes and a focus on surrogate endpoints such as cardiac biomarkers, left ventricular ejection fraction, or scar size”

direct quote[Introduction]

“Building on these insights, we designed a phase 3 clinical trial with long term follow-up to assess the effect of intracoronary infusion of Wharton’s jelly derived mesenchymal stem cells on the development of post-myocardial infarction heart failure.”

direct quote[Introduction]

“The BAMI trial, the largest phase 3 trial in this area, used total mortality as its primary endpoint but did not show a significant benefit”

Randomization method (permuted block, size six, web-based) and unit (patient) are stated. Blinding is single-blind with a stated rationale (sham not permitted) and explicit blinding of outcome assessors and analysts. Sample size was calculated a priori with assumed event rates and an events requirement. Inclusion/exclusion criteria are pre-specified. The analysis population and handling of withdrawals are described. Applicable sub-criteria are all adequate.

Sub-criteria

controlsN/A

power analysisADEQUATE

blinding levelsADEQUATE

outlier handlingADEQUATE

randomization unitADEQUATE

inclusion exclusionADEQUATE

randomization methodADEQUATE

replicate distinctionN/A

independent replicationN/A

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 90% conf

The trial uses a sound design with central permuted-block randomization, clear blinding of outcome assessors, a priori sample-size calculation, pre-specified inclusion/exclusion criteria, and a defined analysis population.

Evidence

direct quote[Methods, Sample size, randomisation, and blinding]

“Randomisation was done centrally at the main study centre by using permuted block randomisation (block size of six), implemented through a web based randomisation system”

direct quote[Methods, Sample size, randomisation, and blinding]

“However, all researchers, clinicians, and staff members responsible for follow-up care, outcome adjudication, and data analysis remained blinded.”

direct quote[Methods, Sample size, randomisation, and blinding]

“We initially calculated the sample size to include approximately 118 patients in the intervention arm and 220 patients in the control arm to detect a difference in heart failure incidence rate, assuming rates of 3.9% in the intervention group and 12% in the control group”

PASSReviewer 2· 90% conf

The study design is adequately described with randomization, blinding, sample size calculation, and inclusion/exclusion criteria.

Evidence

direct quote[Methods, Sample size, randomisation, and blinding]

“Randomisation was done centrally at the main study centre by using permuted block randomisation (block size of six), implemented through a web based randomisation system ( https://www.sealedenvelope.com/randomisation/simulation/ ).”

direct quote[Same section]

“However, all researchers, clinicians, and staff members responsible for follow-up care, outcome adjudication, and data analysis remained blinded.”

direct quote[Same section]

PASSReviewer 3· 90% conf

Core design elements for a human RCT are reported: central permuted-block randomisation, explicit blinding strategy, pre-specified eligibility criteria, analysis population, and sample-size planning; alpha/power are not explicitly stated, though details are referenced to supplementary materials.

Evidence

direct quote[Methods, 'Sample size, randomisation, and blinding']

“However, all researchers, clinicians, and staff members responsible for follow-up care, outcome adjudication, and data analysis remained blinded.”

direct quote[Methods, 'Sample size, randomisation, and blinding']

The paper reports sex, age, and various health indicators in baseline characteristics. Both sexes are included, so sex justification is not required. All applicable sub-criteria are adequately reported.

Sub-criteria

demographicsADEQUATE

sex reportedADEQUATE

sex justifiedN/A

age weight healthADEQUATE

housing conditionsN/A

species strain sourceN/A

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 90% conf

Biological variables are well reported for a human trial: sex, age, BMI, and comprehensive medical history are given, and the cohort is mixed-sex.

Evidence

direct quote[Results, Baseline characteristics]

“Most patients were male: 85% in the intervention group and 79% in the control group.”

direct quote[Table 1]

“Mean (SD) age, years | 57.8 (10.7) | 59.2 (10.9) | 58.7 (10.8)”

PASSReviewer 2· 95% conf

Sex, age, health status, and demographics are adequately reported in Table 1.

Evidence

paraphrase[Table 1]

“Male sex: 115 (85%) intervention, 205 (79%) control.”

paraphrase[Table 1]

“Mean (SD) age, years: 57.8 (10.7) intervention, 59.2 (10.9) control.”

paraphrase[Table 1]

“Table 1 includes smoking, BMI, medical history, and baseline health indicators.”

PASSReviewer 3· 80% conf

Sex, age, body-mass index, and extensive medical history are reported; race/ethnicity is not reported.

Evidence

direct quote[Results, 'Baseline characteristics']

“Most patients were male: 85% in the intervention group and 79% in the control group.”

direct quote[Results, 'Baseline characteristics']

“The mean age of participants was similar in the two groups: 57.8 (standard deviation 10.7) years for the intervention group and 59.2 (10.9) years for the control group.”

absence[Table 1 / baseline characteristics]

Race/ethnicity is not reported.

The protocol received approval from a named ethics committee with approval code IR.SUMS.REC.1400.409. Informed consent was obtained from all patients, and the consent process is described. Regulatory compliance with the Declaration of Helsinki is stated. All applicable criteria are adequate.

Sub-criteria

iacuc statementN/A

informed consentADEQUATE

irb ethics statementADEQUATE

regulatory complianceADEQUATE

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 95% conf

Ethics approval with a protocol number, informed consent, and Declaration of Helsinki compliance are all explicitly stated.

Evidence

direct quote[Ethics statements]

“The study protocol received approval from the local institutional review board and ethics committee (approval code: IR.SUMS.REC.1400.409)”

direct quote[Ethics statements]

“Informed consent was obtained from all patients.”

PASSReviewer 2· 95% conf

Ethics approval, informed consent, and regulatory compliance are clearly stated.

Evidence

paraphrase[Ethics statements]

“The study protocol received approval from the local institutional review board and ethics committee (approval code: IR.SUMS.REC.1400.409).”

direct quote[Methods, Consent]

“All patients gave informed consent.”

direct quote[Ethics statements]

“The trial adhered to the principles outlined in the Declaration of Helsinki.”

PASSReviewer 3· 85% conf

Ethical approval, informed consent, and Declaration of Helsinki compliance are reported with an approval code and trial registration.

Evidence

direct quote[Ethics statements, 'Ethical approval']

“The study protocol received approval from the local institutional review board and ethics committee (approval code: IR.SUMS.REC.1400.409)”

direct quote[Ethics statements, 'Ethical approval']

“Informed consent was obtained from all patients.”

direct quote[Ethics statements, 'Ethical approval']

“The trial adhered to the principles outlined in the Declaration of Helsinki.”

The paper describes the source, isolation, characterization, and quality control of Wharton's jelly derived MSCs. Stata version 18 is identified for statistical analysis. No other biological resources are applicable.

Sub-criteria

mycoplasma testingN/A

reagents identifiedADEQUATE

organisms identifiedN/A

antibodies identifiedN/A

cell line authenticationN/A

software tools identifiedADEQUATE

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 85% conf

The investigational biologic (MSCs) is well characterized, and the statistical software is identified; the bench-style criteria are not applicable to this clinical trial.

Evidence

direct quote[Methods, Intracoronary infusion of mesenchymal stem cells]

“Clinical grade, current good manufacturing practice certified allogenic human Wharton’s jelly derived mesenchymal stem cells were transported to the hospital on the day of the infusion and suspended in 0.9% saline.”

direct quote[Methods, Statistical analysis]

“We used Stata version 18 for all statistical analysis.”

PASSReviewer 2· 90% conf

The investigational product (MSCs) is described in detail, and statistical software is identified.

Evidence

paraphrase[Methods, Intracoronary infusion of mesenchymal stem cells]

“Intracoronary infusion of an estimated 10 7 Wharton's jelly derived mesenchymal stem cells in the cardiac catheterisation laboratory. Clinical grade, current good manufacturing practice certified allogenic human Wharton's jelly derived mesenchymal stem cells were transported to the hospital on the day of the infusion and suspended in 0.9% saline.”

direct quote[Methods, Statistical analysis]

“We used Stata version 18 for all statistical analysis.”

WARNReviewer 3· 70% conf

The investigational MSC product is described in terms of source, dose, and delivery, and Stata 18 is identified, but the product's manufacturer/lot, antibody identifiers for flow cytometry, and mycoplasma testing are not reported.

Evidence

direct quote[Methods, 'Intracoronary infusion of mesenchymal stem cells']

“flow cytometry analysis showed the expression of surface markers CD105, CD73, and CD90, whereas the cells were negative for CD45, CD34, CD11b, CD31, and HLA-DR”

absence[Methods, 'Intracoronary infusion of mesenchymal stem cells']

Mycoplasma testing is not reported.

Statistical tests are named extensively, exact p-values are given for most endpoints, effect sizes with CIs are reported, software is identified, and data presentation follows the clinical-trial idiom. However, Table 1 contains an arithmetic impossibility: 'eGFR <60 mm/min/1.73 m2 | 18 (134) | 39 (1) | 57 (14)' — the percentages 134% and 1% are impossible for n=136 and n=260. This is a demonstrable data-reporting error, so the dimension is rated warn rather than pass.

Sub-criteria

tests namedADEQUATE

exact p valuesADEQUATE

effect sizes ciADEQUATE

data presentationINADEQUATE

software identifiedADEQUATE

assumptions verifiedADEQUATE

mathematical plausibilityWARN

Per reviewer (3) — the votes behind the verdict

WARNReviewer 1· 80% conf

The statistical analysis is generally rigorous and well reported, but a demonstrable typographical error in Table 1 (impossible percentages for eGFR <60) lowers the overall rating.

Evidence

direct quote[Abstract]

“hazard ratio 0.43, 95% confidence interval 0.21 to 0.89; P=0.024”

direct quote[Table 1]

“eGFR <60 mm/min/1.73 m 2 | 18 (134) | 39 (1) | 57 (14)”

WARNReviewer 2· 80% conf

Statistical tests are named, assumptions verified, exact p-values and effect sizes with CIs reported, software identified, and data presentation adequate. However, a arithmetic discrepancy in the reported incidence rate for the primary endpoint raises concern.

Evidence

paraphrase[Table 2]

“HF incidence (development): Intervention: 9 events/314.47 person-years, annual incidence rate 2.77% (1.44 to 5.32); Control: 37 events/551.88 person-years, annual incidence rate 6.48% (4.69 to 8.94).”

paraphrase[Abstract, Results]

“P=0.024, P=0.015, P=0.012, etc.”

direct quote[Results]

“hazard ratio 0.43, 95% confidence interval 0.21 to 0.89”

WARNReviewer 3· 75% conf

Statistical methods are comprehensive and mostly well reported, but there is an arithmetic inconsistency between the HF-incidence event counts/person-years and the reported rates in Table 2/Abstract, and the composite HR is reported as both 0.39 and 0.40.

Evidence

direct quote[Methods, 'Statistical analysis']

“We used Stata version 18 for all statistical analysis.”

direct quote[Table 2]

“9/314.47 | 5.74 (1.99 to 9.50) | 2.77 (1.44 to 5.32) | 37/551.88 | 16.08 (10.90 to 21.27 | 6.48 (4.69 to 8.94)”

direct quote[Abstract and Results, 'Endpoint analysis']

“0.39, 0.19 to 0.82; P=0.012”

The paper ends with 'Data availability statement De-id' which is incomplete and does not provide a concrete access route. No repository deposit or accession numbers are provided. Code sharing is not applicable but the lack of a proper data availability statement constitutes a fail.

Sub-criteria

code sharingN/A

accession numbersN/A

repository depositN/A

data availability statementNOT REPORTED

Per reviewer (3) — the votes behind the verdict

FAILReviewer 1· 80% conf

A data availability statement is present but truncated/vague, and no repository deposit or code sharing is reported.

Evidence

direct quote[Data availability statement]

“Data availability statement De-id”

direct quote[Results, Endpoint analysis]

“An interactive version of this graphic and downloadable data are available at https://public.flourish.studio/visualisation/25452455/”

FAILReviewer 2· 95% conf

The data availability statement is incomplete (appears truncated), and no code is shared. For a clinical trial, a proper data availability statement is required.

Evidence

direct quote[End of paper before references]

“Data availability statement De-id”

WARNReviewer 3· 60% conf

A data availability statement begins but its full text is not visible in the provided excerpt; figure-level data are shared via Flourish URLs, but no repository/accession or code is identified.

Evidence

direct quote[End of manuscript, 'Data availability statement']

“Data availability statement De-id”

direct quote[Results, 'Endpoint analysis']

“An interactive version of this graphic and downloadable data are available at https://public.flourish.studio/visualisation/25452455/”

absence[Methods, 'Statistical analysis']

Custom analysis code is not shared.

All seven applicable sub-criteria are adequately reported. The trial is registered, CONSORT guidelines are followed, all pre-specified outcomes are reported, limitations are discussed, conclusions are proportional, and funding and competing interests are disclosed.

Sub-criteria

funding coiADEQUATE

trial registrationADEQUATE

reporting guidelineADEQUATE

methods completenessADEQUATE

all outcomes reportedADEQUATE

limitations discussedADEQUATE

conclusions proportionalADEQUATE

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 90% conf

The manuscript is transparent: trial registration, CONSORT adherence, complete reporting of outcomes, limitations, and funding/COI statements are all present.

Evidence

direct quote[Abstract]

“Trial registration ClinicalTrials.gov NCT05043610 .”

direct quote[Methods]

“This manuscript has been prepared in adherence to the Consolidated Standards of Reporting Trials (CONSORT) guidelines.”

direct quote[Discussion, Strengths and limitations of study]

“The limitations of this study include the inability to do a sham procedure for the control group, which would have allowed for a double blinded study design instead of a single blinded format.”

PASSReviewer 2· 95% conf

The paper is well-reported with detailed methods, trial registration, CONSORT adherence, all outcomes reported, limitations discussed, proportional conclusions, and funding/COI statements.

Evidence

direct quote[Abstract, Methods]

“Trial registration ClinicalTrials.gov NCT05043610 .”

direct quote[Methods]

“This manuscript has been prepared in adherence to the Consolidated Standards of Reporting Trials (CONSORT) guidelines.”

paraphrase[Discussion, Strengths and limitations]

“The limitations of this study include the inability to do a sham procedure for the control group...”

PASSReviewer 3· 90% conf

The manuscript is transparent: registered, CONSORT-adherent, reports all pre-specified endpoints including null results, discusses limitations, and gives funding/COI.

Evidence

direct quote[Abstract and Ethics statements]

“ClinicalTrials.gov with the identifier NCT05043610”

direct quote[Methods, first paragraph]

“This manuscript has been prepared in adherence to the Consolidated Standards of Reporting Trials (CONSORT) guidelines.”

direct quote[Discussion, 'Strengths and limitations of study']

“The limitations of this study include the inability to do a sham procedure for the control group, which would have allowed for a double blinded study design instead of a single blinded format.”

12 copyedit issues flagged (5 major): mostly consistency, typo, clarity.

Checked 36 references by DOI: 35 verified — 1 lookup failed.

Reproducibility

2 data/code links checked; 2 live.

Registered (1 ID: ClinicalTrials.gov). Reporting guideline cited: CONSORT.

Αlpha¹ Rigor Action ItemsFinal pass before journal submission

This is a published paper with significant reporting issues that warrant a correction. An informed reader should weigh the arithmetic inconsistencies in Table 2 (HF incidence rates) and the abstract/results HR discrepancy before relying on the reported effect sizes. The truncated data availability statement and the contradictory safety statement ('No adverse events were noticed') are additional concerns. An erratum or a letter to the editor addressing these issues would improve the record.

1.
HIGHstatistics
Correct the arithmetic error in Table 2 for the HF incidence rates: the reported rates (2.77% and 6.48%) do not match the calculation from events and person-years (9/314.47=2.86%, 37/551.88=6.70%). Clarify the person-years denominator used or correct the rates.
This is a demonstrable data-reporting error that undermines the reliability of the primary endpoint results.
2.
HIGHreporting
Harmonize the composite-endpoint hazard ratio between the abstract (0.39) and the results text (0.40) and ensure the corresponding P value and confidence interval are consistent.
Internal inconsistency in a key result can confuse readers and may indicate a calculation error.
3.
HIGHdata code
Complete the data availability statement with a concrete access route (e.g., de-identified participant data available on reasonable request with a named repository or a data-access committee).
The current truncated statement ('Data availability statement De-id') is insufficient for a published clinical trial and violates CONSORT reporting standards.
4.
HIGHreporting
Correct the safety statement 'No adverse events were noticed' to either qualify it as 'no intervention-related adverse events' or provide a full adverse-event table, as the trial reports deaths and heart failure events as endpoints.
The current statement is directly contradicted by the trial's own endpoint events, which is a serious reporting inconsistency.
5.
HIGHstatistics
Correct the impossible percentage values in Table 1 for the eGFR <60 row (134% and 1% are impossible; likely they should be 13% and 15%).
This is a clear typographical error that distorts the baseline characteristics table.
6.
HIGHreporting
Explicitly state the alpha level (e.g., α=0.05) and statistical power (e.g., 80%) used in the sample-size calculation in the Methods section.
These parameters are standard for reporting a power analysis and their absence is a minor reporting gap.
7.
HIGHrigor
Add the manufacturer/source, lot/batch number, and release criteria for the Wharton's jelly-derived MSCs in the Methods section, including a statement on mycoplasma testing.
The investigational product is a key resource; missing details limit reproducibility and the ability to assess product consistency.
8.
HIGHrigor
Provide flow-cytometry antibody details (clone, vendor, catalog number) for the cell surface markers used in product characterization.
Antibody clone and vendor information is essential for reproducibility of the product characterization.
9.
MEDIUMother
Add race/ethnicity (or a justification for its omission) to Table 1 for completeness of demographic reporting.
While not always mandatory, race/ethnicity is a standard demographic variable that may be relevant for generalizability.
10.
MEDIUMcopyedit
Fix the typo 'conduced' to 'conducted' in the Patient care section.
Minor typographical error that should be corrected.
11.
MEDIUMcopyedit
Add the missing closing parenthesis in Table 2 for the row '16.08 (10.90 to 21.27' to read '16.08 (10.90 to 21.27)'.
Missing parenthesis is a formatting error that could cause confusion.
12.
LOWother
Consider depositing de-identified participant-level data in a recognized repository and sharing the Stata analysis code (do-files) on a public repository (e.g., GitHub with a DOI) to enhance reproducibility.
This is a best practice for open science and would strengthen the paper's transparency.

Full text (58,902 chars)Analyzed: Aug 5, 2026

Start the discussion on JRNLClub

Community discussion on jrnlclub.com

Read alongside