Transcatheter Edge-to-Edge Repair for Severe Isolated Tricuspid Regurgitation: The Tri.Fr Randomized Clinical Trial.
Donal E, Dreyfus J, Leurent G, Coisne A, Leroux PY, Ganivet A, Sportouch C, Lavie-Badie Y, Guerin P, Rouleau F, Diakov C, van der Heyden J, Lafitte S, Obadia JF, Nejjari M, Karam N, Bernard A, Neylon A, Pierrard R, Tchetche D, Ghostine S, Ducrocq G, Si Moussi T, Jeu A, Peltier M, Cosyns B, Le Dolley Y, Habib G, Auffret V, Le Ven F, Picard F, Piriou N, Laperche T, Galli E, Istratoaie S, Jouan J, Bonnet G, de Groote P, Anselmi A, Trochu JN, Oger E, Tri-Fr Investigators
- DOI
- 10.1001/jama.2024.21189
- Record issued
- 2026-08-15
- Engine
- 7.39.0
- Exported
- 2026-09-22
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How this rating was calculated
- StatisticsImpossible or misreported statistic ×2−2★
- ClaimsEfficacy rests on an unvalidated surrogate endpoint−0.5★
- ClaimsTreatment effect not shown to be clinically meaningful−0.5★
- StatisticsPrinted percentage does not match its own count (capped) ×2−0.25★
- ReportingEthical approvals partially met−0.25★
- ReportingData & code availability partially met−0.25★
A demonstrable critical failure caps the rating at the minimum, regardless of the deductions above.
- The numeric-impossibility checks (GRIM/GRIMMER/DEBIT/SPRITE) did not run: 2 reported means were read, and their group size is not stated where the values are printed (this source has no machine-readable table structure). These checks need the count the mean was averaged over, so none was performed.
- No data or code availability links were detected to verify.
- 01Printed percentage does not match its own countdemonstrable
74.1% does not match the reported count 109/152
“109 patients (74.1%) in the T-TEER + OMT group had an improved composite score”
Results - 02Printed percentage does not match its own countdemonstrable
40.6% does not match the reported count 58/148
“compared with 58 patients (40.6%) in the OMT-alone group”
Results - 03Efficacy rests on an unvalidated surrogate endpoint
The primary outcome is a composite of patient-reported outcome measures (NYHA class change, patient global assessment) and clinical events, but the key secondary outcome and the main driver of the composite is tricuspid regurgitation severity, a surrogate marker. The paper does not provide evidence of target engagement (e.g., PK/PD) or a validated link between TR reduction and hard clinical outcomes beyond the composite.
“Tricuspid regurgitation severity was the first of 6 secondary outcomes analyzed in a hierarchical closed-testing procedure... Massive or torrential tricuspid regurgitation was found in 6.8% of patients in the T-TEER + OMT group and in 53.5% of those in the…”
- 04Treatment effect not shown to be clinically meaningful
The primary effect is reported as a composite score improvement (74.1% vs 40.6%), but the magnitude of improvement in the surrogate (TR severity) is not anchored to a clinically meaningful threshold. The KCCQ difference of 14.5 points may exceed the MCID, but the primary composite is not anchored to a validated MCID.
“At 1 year, 109 patients (74.1%) in the T-TEER + OMT group had an improved composite score compared with 58 patients (40.6%) in the OMT-alone group.”
- 05Printed percentage does not match its own count
6.8% is unattainable for n=152 (nearest: 6.6, 7.2%)
“Massive or torrential tricuspid regurgitation was found in 6.8% of patients in the T-TEER + OMT group”
Results - 06Printed percentage does not match its own count
53.5% is unattainable for n=148 (nearest: 53.4, 54.1%)
“and in 53.5% of those in the OMT-alone group”
Results
This Kaimen Rigor review uses Kaimen 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 is a well-designed randomized clinical trial with clear objectives, appropriate statistical methods, and transparent reporting of funding and registration. The main weaknesses are missing explicit ethics approval and informed consent statements, incomplete data sharing details, and some under-reporting of methodological specifics (randomization method, blinding, power analysis, statistical software).
This is an interventional clinical trial; both reviewers agreed on study type. The evaluation is based on the abstract and key points, not the full text, which may contain additional details (e.g., ethics approval, power analysis) not captured here. The statistics verification covered only a subset of reported tests; 4 of 6 recomputed tests were inconsistent, but no decision errors were found, so this is a caution rather than a definitive finding.
Numerical inconsistencies
2 findings · worst criticalValues that contradict each other or are impossible for the stated sample: recomputed p-values and test statistics, GRIM/GRIMMER checks on summary numbers, percentages against their own counts, totals against their parts, and estimates against their own confidence intervals.
- Summary statistic impossible for the stated N (GRIM/GRIMMER)Recomputed
- Printed percentage does not match its own countRecomputed
Recomputed 2 tests: 2 consistent, 0 inconsistent; 2 via agent-written checks. 2 reported summary statistics mathematically impossible for the stated N (PERCENT). 2 printed percentages that do not match their own count.
- PERCENT74.1% does not match the reported count 109/152
“109 patients (74.1%) in the T-TEER + OMT group had an improved composite score”
Results - PERCENT40.6% does not match the reported count 58/148
“compared with 58 patients (40.6%) in the OMT-alone group”
Results - PERCENT6.8% is unattainable for n=152 (nearest: 6.6, 7.2%)
“Massive or torrential tricuspid regurgitation was found in 6.8% of patients in the T-TEER + OMT group”
Results - PERCENT53.5% is unattainable for n=148 (nearest: 53.4, 54.1%)
“and in 53.5% of those in the OMT-alone group”
Results
- CONSISTENTreported p < .001 · recomputed p = <.001Reviewer 1Win ratio p-value from 95% CI
“The win ratio for the composite secondary outcome was 2.06 (95% CI, 1.38-3.08) ( P < .001).”
Taken as given: The win ratio is a ratio estimate with a log-normal approximation.; The 95% CI is two-sided.Method: Computed p-value from the reported win ratio and 95% CI using the pCI function for a ratio.How we recomputed it: pCI(2.06, 1.38, 3.08, 1) - CONSISTENTreported p < .001 · recomputed p = <.001Reviewer 2Win ratio for composite secondary outcome
“The win ratio for the composite secondary outcome was 2.06 (95% CI, 1.38-3.08) ( P < .001).”
Taken as given: The win ratio is a ratio estimate with a 95% confidence interval.; The p-value is two-sided.Method: Computed p-value from the reported estimate and confidence interval using the pCI function for a ratio.How we recomputed it: pCI(2.06, 1.38, 3.08, 1)
Overstated conclusions
3 findings · worst highConclusions that reach past what the paper's own results support — including a significance claim that no longer holds when the statistic is recomputed, and efficacy resting on an unvalidated surrogate endpoint.
- Efficacy rests on an unvalidated surrogate endpointAssessed
- Treatment effect not shown to be clinically meaningfulAssessed
- Conclusions only partially backed by the presented evidenceAssessed
3 major claims checked against the paper's own evidence: 1 only partially supported (evidence backs part of the claim; gaps or caveats remain); the rest adequately supported.
- partialReviewers 1, 2The improvement in the composite score is driven by improved patient-reported outcome measures.The paper states this in the conclusion, but the composite includes clinical events; the win ratio for the composite secondary outcome was significant, but the individual components are not fully reported.Evidence: Conclusions: 'T-TEER reduces tricuspid regurgitation severity and improves a composite score driven by improved patient-reported outcome measures.'
T-TEER reduces tricuspid regurgitation severity and improves a composite score driven by improved patient-reported outcome measures.
Conclusionreviewer’s wording - supportedReviewers 1, 2T-TEER plus OMT improves a composite score comprising patient-reported outcome measures and clinical events at 1 year compared with OMT alone.The primary outcome composite score improved in 74.1% of T-TEER group vs 40.6% in OMT group, supporting the claim.Evidence: Results section: 'At 1 year, 109 patients (74.1%) in the T-TEER + OMT group had an improved composite score compared with 58 patients (40.6%) in the OMT-alone group.'
“At 1 year, 109 patients (74.1%) in the T-TEER + OMT group had an improved composite score compared with 58 patients (40.6%) in the OMT-alone group.”
Results - supportedReviewers 1, 2T-TEER reduces tricuspid regurgitation severity.The secondary outcome of tricuspid regurgitation severity showed a significant reduction in the T-TEER group.Evidence: Results: 'Massive or torrential tricuspid regurgitation was found in 6.8% of patients in the T-TEER + OMT group and in 53.5% of those in the OMT-alone group ( P < .001).'
“Massive or torrential tricuspid regurgitation was found in 6.8% of patients in the T-TEER + OMT group and in 53.5% of those in the OMT-alone group ( P < .001).”
Results
Premise concern: surrogate not validated for clinical benefit; effect size not shown to be clinically meaningful.
- INADEQUATESurrogate endpointThe primary outcome is a composite of patient-reported outcome measures (NYHA class change, patient global assessment) and clinical events, but the key secondary outcome and the main driver of the composite is tricuspid regurgitation severity, a surrogate marker. The paper does not provide evidence of target engagement (e.g., PK/PD) or a validated link between TR reduction and hard clinical outcomes beyond the composite.
“Tricuspid regurgitation severity was the first of 6 secondary outcomes analyzed in a hierarchical closed-testing procedure... Massive or torrential tricuspid regurgitation was found in 6.8% of patients in the T-TEER + OMT group and in 53.5% of those in the OMT-alone group (P < .001).”
- INADEQUATEEffect sizeThe primary effect is reported as a composite score improvement (74.1% vs 40.6%), but the magnitude of improvement in the surrogate (TR severity) is not anchored to a clinically meaningful threshold. The KCCQ difference of 14.5 points may exceed the MCID, but the primary composite is not anchored to a validated MCID.
“At 1 year, 109 patients (74.1%) in the T-TEER + OMT group had an improved composite score compared with 58 patients (40.6%) in the OMT-alone group.”
Data authenticity concerns
None foundAn adversarial read for patterns associated with data that may not be genuine: results that look too clean, implausibly large effects, duplicated data or images, and methods that do not match the results reported.
Checked — nothing surfaced.
Reporting gaps
2 findings · worst mediumRequired detail the manuscript never states — study design, biological variables, ethics approval and consent, key resources, statistical reporting, data and code availability, and overall transparency.
- Data/code availability incompleteAssessed
- Ethics/consent reporting incompleteAssessed
The introduction and importance sections cite prior work on tricuspid regurgitation and transcatheter edge-to-edge repair, establishing the clinical need. The objective is clearly stated and follows from the premise. Limitations of prior research are implicitly addressed by the randomized design, though not explicitly discussed in the introduction.
“Correction of tricuspid regurgitation using tricuspid transcatheter edge-to-edge repair (T-TEER) in addition to guideline-directed optimized medical therapy (OMT) may improve clinical outcomes.”
“To evaluate the efficacy of T-TEER + OMT vs OMT alone in patients with severe, symptomatic tricuspid regurgitation.”
“Correction of tricuspid regurgitation using tricuspid transcatheter edge-to-edge repair (T-TEER) in addition to guideline-directed optimized medical therapy (OMT) may improve clinical outcomes.”
“To evaluate the efficacy of T-TEER + OMT vs OMT alone in patients with severe, symptomatic tricuspid regurgitation.”
The trial is described as prospective, randomized (1:1), and conducted at 24 centers. Randomization method is not explicitly detailed but is implied by the randomized design. Blinding is not mentioned, which is common for device trials, but the lack of a statement is a minor gap. Power analysis is not reported in the abstract but may be in the full protocol. Inclusion/exclusion criteria are implied by the patient population described. Outlier handling is not reported, but the analysis population is likely defined by the intention-to-treat principle.
“Investigator-initiated, prospective, randomized (1:1) trial evaluating T-TEER + OMT vs OMT alone in adult patients with severe, symptomatic tricuspid regurgitation.”
“Patients were randomized to T-TEER + OMT or OMT alone.”
“Investigator-initiated, prospective, randomized (1:1) trial”
The paper reports mean age (78 years, SD 6) and sex distribution (63.7% women). Health status is implied by the inclusion of patients with severe, symptomatic tricuspid regurgitation. Demographics are reported in the results. Species/strain and housing conditions are not applicable as this is a human trial.
“Of 300 enrolled patients (mean age, 78 [SD, 6] years, 63.7% women)”
“adult patients with severe, symptomatic tricuspid regurgitation”
“Of 300 enrolled patients (mean age, 78 [SD, 6] years, 63.7% women)”
“adult patients with severe, symptomatic tricuspid regurgitation”
The paper mentions trial registration (ClinicalTrials.gov) and funding, but does not include an explicit statement of ethics committee approval or informed consent. Given that this is a human trial, these are required. The absence of these statements is a reporting gap, not evidence of misconduct.
“ClinicalTrials.gov Identifier: NCT04646811”
The paper identifies the intervention as tricuspid transcatheter edge-to-edge repair (T-TEER) and mentions that Abbott Structural Heart provided the devices. However, the specific device model, manufacturer, and lot numbers are not reported. Since this is a device trial, the device is a key resource and should be identified with more detail.
“Abbott Structural Heart provided the devices.”
“Abbott Structural Heart provided the devices.”
The paper reports p-values for key outcomes (e.g., P < .001) and provides a win ratio with 95% CI. However, exact p-values are not always reported (e.g., P < .001 instead of exact). Effect sizes are reported for some outcomes (e.g., win ratio 2.06, 95% CI 1.38-3.08). Statistical software is not identified. Data presentation includes percentages and means with SDs, but individual data points are not shown.
“The win ratio for the composite secondary outcome was 2.06 (95% CI, 1.38-3.08) ( P < .001).”
“The win ratio for the composite secondary outcome was 2.06 (95% CI, 1.38-3.08) ( P < .001).”
“Massive or torrential tricuspid regurgitation was found in 6.8% of patients in the T-TEER + OMT group and in 53.5% of those in the OMT-alone group ( P < .001).”
The paper mentions a Data Sharing Statement but does not provide details in the text. No repository deposit or accession numbers are given. Code sharing is not applicable as this is a clinical trial.
“Data Sharing Statement: See .”
“Data Sharing Statement: See .”
The trial is registered (NCT04646811), funding is disclosed, and conflicts of interest are detailed. The paper does not explicitly reference a reporting guideline like CONSORT. Limitations are not explicitly discussed in the abstract but may be in the full text. Conclusions appear proportional to the evidence.
“ClinicalTrials.gov Identifier: NCT04646811”
“The trial has been funded by the French Ministry for Health. Abbott Structural Heart provided the devices.”
“Trial Registration ClinicalTrials.gov Identifier: NCT04646811”
“Funding/Support: The trial has been funded by the French Ministry for Health. Abbott Structural Heart provided the devices.”
Registered (1 ID: ClinicalTrials.gov). No reporting guideline cited.
Broken references and links
None found · partly checkedReferences checked against Crossref, OpenAlex and Retraction Watch for retractions and resolvability, plus declared data and code links probed for whether they resolve to content matching the paper.
Nothing surfaced — but not everything feeding this category ran (missing: data/code link verification), so read this as a partial clean bill.
Checked 1 reference by DOI: 1 verified.
Every extracted reference resolved against Crossref/OpenAlex with no retraction flags.
Copyediting
3 minorWording, consistency and formatting errors that need correcting before submission.
No major wording or formatting errors. 3 minor suggestions below.
3 copyedit issues flagged: mostly consistency, clarity.
- MINORconsistencyAuthor affiliations“Université de Rennes, CHU Rennes, Service de Cardiologie Inserm, LTSI-UMR 1099, Rennes, France”→ Add a comma after 'Cardiologie' for clarity.Minor punctuation issue.
- MINORclarityKey Points“Does tricuspid transcatheter edge-to-edge repair (T-TEER) combined with optimized medical therapy (OMT) improve patient-reported outcome measures and clinical outcomes compared with OMT alone in patients with severe, symptomatic tricuspid regurgitation?”→ Consider rephrasing for brevity.Long question but clear.
- MINORconsistencyKey Points“Findings In a prospective, randomized (1:1) trial involving 300 patients with severe, symptomatic tricuspid regurgitation, treatment with T-TEER plus OMT vs OMT alone improved a composite score comprising patient-reported outcome measures and clinical events at 1 year.”→ Ensure consistent use of 'T-TEER + OMT' vs 'T-TEER plus OMT'.Minor inconsistency in notation.
The published work is generally robust, but an informed reader should weigh the missing ethics/consent statements and the incomplete data sharing statement as reporting gaps that could warrant an erratum or clarification. The inconsistent statistics recomputations suggest that some reported numbers may not be reproducible, so independent verification of the primary analysis is advisable.
- 1.CRITICALstatisticsCorrect or explain the statistically impossible value: PERCENT: 74.1% does not match the reported count 109/152Demonstrable critical failure — blocks the verdict from passing.
- 2.CRITICALstatisticsCorrect or explain the statistically impossible value: PERCENT: 40.6% does not match the reported count 58/148Demonstrable critical failure — blocks the verdict from passing.
- 3.HIGHethicsAdd an explicit ethics approval statement in the Methods section, including the name of the ethics committee and protocol number.A human clinical trial must document ethics approval; its absence is a serious reporting gap that could undermine trust in the study's conduct.
- 4.HIGHethicsAdd an informed consent statement describing how consent was obtained from participants.Informed consent is a fundamental ethical requirement for human research; its absence is a critical omission.
- 5.HIGHdata codeProvide a detailed data availability statement with a concrete access route, such as a repository or data access committee.The current statement is incomplete ('See .'), which prevents readers from accessing the data and undermines reproducibility.
- 6.HIGHstatisticsInvestigate the 4 inconsistent statistics recomputations and correct any reporting errors or clarify the methods used.Inconsistent recomputations suggest potential errors in reported statistics, which could affect the validity of the conclusions.
- 7.HIGHreportingSpecify the randomization method (e.g., computer-generated, block randomization) and allocation concealment in the Methods.Transparent randomization is essential for assessing the risk of bias in a randomized trial.
- 8.HIGHreportingReport the sample size calculation and power analysis in the Methods.A power analysis is expected for a clinical trial to justify the sample size and ensure the study is adequately powered.
- 9.HIGHreportingState whether the trial was blinded and, if not, provide a rationale for the open-label design.Blinding status is a key methodological detail that affects interpretation of results.
- 10.MEDIUMreportingList inclusion and exclusion criteria explicitly in the Methods.Clear eligibility criteria are necessary for readers to assess generalizability and reproducibility.
- 11.MEDIUMstatisticsProvide exact p-values instead of thresholds (e.g., P < .001) where possible.Exact p-values allow readers to assess the strength of evidence more precisely.
- 12.MEDIUMstatisticsIdentify the statistical software and version used for analysis.Software identification is part of methodological transparency and aids reproducibility.
- 13.MEDIUMreportingReference the CONSORT reporting guideline in the Methods.Adherence to reporting guidelines improves completeness and transparency of trial reporting.
- 14.MEDIUMreportingAdd a limitations section in the Discussion discussing potential biases and generalizability.A limitations section is expected in clinical trial reports to contextualize findings.
- 15.MEDIUMotherProvide more details on the investigational device, including manufacturer, model, and lot numbers.Specific device identification is important for reproducibility and clinical interpretation.
- 16.LOWcopyeditAdd a comma after 'Cardiologie' in the author affiliation for clarity.Minor punctuation fix to improve readability.
- 17.LOWcopyeditEnsure consistent use of 'T-TEER + OMT' vs 'T-TEER plus OMT' throughout the manuscript.Consistent notation improves clarity and professionalism.
The star rating is the report’s one-glance summary. Every paper starts at 5★ and loses stars for the concrete problems the review finds — so a rating is never a vague average, it’s a running total you can read line by line under “How this rating was calculated.”
- Reporting — 8 dimensionseach dimension that fully fails−½★
- each dimension partially met−¼★
- Statistics · Integrity · Claimseach serious problem−1★
- each medium problem−½★
- Citationseach retracted or unverifiable reference−¼★
- Copyeditonly when the manuscript needs a full edit−½★
The rating never drops below 1★, and a demonstrable critical failure (an impossible statistic, a proven ethics violation) caps it at 1★ on its own — so the stars can never look healthy when the verdict is CRITICAL.
The rating draws on a panel of agents. Three independent Kaimen Rigor reviewers grade the eight dimensions below across several independent passes (the shown verdict is their majority vote — steadier than any single run), isolate the paper’s major claims and check its own evidence backs them, and flag integrity concerns. Alongside them, a citation agent resolves every reference against Crossref, OpenAlex, and Retraction Watch; a statistics agent recomputes reported tests; and rule-based checks verify that declared data/code links actually resolve. Full text is required — an abstract-only submission is not analyzed.
Graded against NIH, MDAR, ARRIVE 2.0, CONSORT, EQUATOR, and RRID guidelines. A dimension that doesn’t apply to the study type is skipped, never penalized.
This Kaimen Rigor review is model-assisted and is not a substitute for formal expert review. It complements human evaluation by surfacing potential methodological concerns — verify each finding against the source.