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Kaimen Rigor review

Endovascular Therapy for Post-Thrombotic Syndrome - A Randomized Trial.

Vedantham S, Kahn SR, Marston WA, Weinberg I, Sista AK, Magnuson EA, Cohen DJ, Wasan SM, Razavi MK, Goldhaber SZ, Sanfilippo KM, Comerota AJ, Azene EM, Chaar CIO, Leung DA, Kolli KP, Kalva SP, Rostambeigi N, Desai A, Desai KR, Tafur AJ, Khalsa B, Majerus E, Wang B, Wang Y, Nieters P, Derfler MC, Oliver A, Hardy C, Bashir R, Winokur R, Weger N, Khaja MS, Sharma A, Mani N, Kavali P, Thukral S, Lake LL, Mikkelsen K, Parpia S, C-TRACT Trial Investigators

DOI: 10.1056/NEJMoa2519001
Record issued: 2026-08-15
Engine: 7.39.0
Exported: 2026-09-22

Prepared by Alpha1. This document is confidential: it is intended for the recipient it was shared with and must not be redistributed. The live record at alpha1science.com/verify/73d884d9-814e-4887-8029-16261a383e68 is authoritative.

Kaimen Rigor review

Kaimen Rigor reviewed

2.75 / 5

Weak — serious problems found

Interventional Study

Critical

High-priority

How this rating was calculated

Started at 5★ — deductions

IntegrityIntegrity concern ×2−1★
ClaimsEfficacy rests on an unvalidated surrogate endpoint−0.5★
ClaimsTreatment effect not shown to be clinically meaningful−0.5★
ReportingData & code availability partially met−0.25★

Model-reported confidence: highReviewer agreement: highEngine: 7.39.0Source: full text

Biggest issues

01Efficacy rests on an unvalidated surrogate endpoint
highOverreachreviewer-assessedFull detail
The primary efficacy claim is based on the Venous Clinical Severity Score (VCSS), a clinical severity scale, and quality-of-life measures (VEINES-QOL, SF-36). These are patient-reported or clinician-assessed symptom/function scales, not hard clinical outcomes like mortality or major clinical events. The paper does not demonstrate target engagement at the tested dose (e.g., PK/PD or dose-exposure) nor cite validated evidence linking VCSS or QOL changes to long-term clinical outcomes such as ulcer healing or prevention of recurrent thrombosis. The VCSS is a surrogate for clinical benefit, and the link to hard outcomes is not established.
“The primary outcome was PTS severity at 6 months post-randomization, assessed with the VCSS by a clinician who was blinded to treatment arm allocation... The VCSS is a validated scoring system designed to assess clinical change in patients with chronic venous…”
Find in source
02Treatment effect not shown to be clinically meaningful
highOverreachreviewer-assessedFull detail
The primary effect is a mean VCSS difference of −2.0 points (from 10.0 to 8.1). The paper acknowledges that the minimal clinically important difference (MCID) for VCSS has not been formally established, and the 2-point difference is half the size of published VCSS score thresholds (4 points apart) that correlate with incremental gradations in clinical severity. Thus, the effect size is small relative to the scale's meaningful change and lacks an anchor to clinical meaningfulness. The QOL improvements (VEINES-QOL +14.5, SF-36 +6.1) are larger but are secondary outcomes and still surrogate measures.
“Although the minimal clinically important difference on the VCSS has not been formally established, the 2-point difference we aimed to detect was half the size of published VCSS score thresholds (4 points apart) that correlate with incremental gradations in…”
Find in source

Findings by category

101ArithmeticNumerical inconsistencies 302OverreachOverstated conclusions 03AuthenticityNone found 104DisclosureReporting gaps 05AvailabilityNone found 06Copyedit6 minor suggestions

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 C-TRACT trial is a well-designed, rigorously analyzed multicenter RCT with strong reporting on most dimensions. The primary gap is the absence of a data availability statement and code sharing, which is a standard expectation for modern clinical trials.

Both independent reviewers agreed on study type (interventional) and on all dimension statuses, with minor divergence on outlier handling (resolved conservatively). The evaluation is based on the full manuscript text; no supplementary materials were reviewed. The statistics verification component checked 8 tests, all consistent, but coverage is limited to tests with a test statistic and df or an effect estimate with CI.

Numerical inconsistencies

1 finding · worst low

Values 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.

Internal contradictions in the reported numbersAssessed

Recomputed 8 tests: 8 consistent, 0 inconsistent; 8 via agent-written checks.

Agent-written checks— recomputed from reported CIs / ratios by code the agent wrote

CONSISTENTreported p = .001 · recomputed p = .001Reviewer 1
Primary outcome: VCSS adjusted difference at 6 months
“VCSS | 8.1 (5.1) | 10.0 (4.9) | −2.0 | −3.2, −0.8 | 0.001”
Find in source
Taken as given: The adjusted difference is -2.0 with 95% CI -3.2 to -0.8; The CI is two-sided at 95%; The p-value is from the same model that produced the CI
Method: p-value derived from estimate and 95% CI using normal approximation (pCI function)
How we recomputed it: pCI(-2.0, -3.2, -0.8, 0)
CONSISTENTreported p < .001 · recomputed p = <.001Reviewer 1
Secondary outcome: VEINES-QOL adjusted difference at 6 months
“VEINES-QOL | 62.8 (24.6) | 48.6 (26.7) | 14.5 | 9.5, 19.4 | <0.001”
Find in source
Taken as given: The adjusted difference is 14.5 with 95% CI 9.5 to 19.4; The CI is two-sided at 95%; The p-value is from the same model that produced the CI
Method: p-value derived from estimate and 95% CI using normal approximation (pCI function)
How we recomputed it: pCI(14.5, 9.5, 19.4, 0)
CONSISTENTreported p < .001 · recomputed p = <.001Reviewer 1
Secondary outcome: SF-36 PCS adjusted difference at 6 months
“SF-36 PCS | 56.0 (16.4) | 49.9 (17.1) | 6.1 | 2.8, 9.3 | <0.001”
Find in source
Taken as given: The adjusted difference is 6.1 with 95% CI 2.8 to 9.3; The CI is two-sided at 95%; The p-value is from the same model that produced the CI
Method: p-value derived from estimate and 95% CI using normal approximation (pCI function)
How we recomputed it: pCI(6.1, 2.8, 9.3, 0)
CONSISTENTreported p = .030 · recomputed p = .041Reviewer 1
Safety outcome: All bleeding risk ratio
“All bleeding | 13 (11.6%) | 4 (3.6%) | 3.22 | 1.07, 9.69 | 0.03”
Find in source
Taken as given: The 13 and 4 are event counts in EVT and No-EVT groups respectively; The group totals are 112 each (13+99=112, 4+108=112); The test is two-sided
Method: Fisher's exact test (mid-p) from 2x2 table cell counts
How we recomputed it: pFisher2x2(13, 99, 4, 108, 0)
CONSISTENTreported p = .001 · recomputed p = .001Reviewer 2
Primary outcome VCSS adjusted difference p-value from CI
“adjusted difference −2.0 points, 95% CI −3.2 to −0.8, p=0.001”
Find in source
Taken as given: The CI is a 95% confidence interval for the adjusted difference.; The difference is on a linear scale (not log).
Method: Two-sided p-value derived from the estimate and 95% CI using normal approximation.
How we recomputed it: pCI(-2.0, -3.2, -0.8, 0)
CONSISTENTreported p < .001 · recomputed p = <.001Reviewer 2
VEINES-QOL adjusted difference p-value from CI
“adjusted difference 14.5 points, 95% CI 9.5 to 19.4, p<0.001”
Find in source
Taken as given: The CI is a 95% confidence interval for the adjusted difference.; The difference is on a linear scale.
Method: Two-sided p-value derived from the estimate and 95% CI using normal approximation.
How we recomputed it: pCI(14.5, 9.5, 19.4, 0)
CONSISTENTreported p < .001 · recomputed p = <.001Reviewer 2
SF-36 PCS adjusted difference p-value from CI
“adjusted difference 6.1 points, 95% CI 2.8 to 9.3, p<0.001”
Find in source
Taken as given: The CI is a 95% confidence interval for the adjusted difference.; The difference is on a linear scale.
Method: Two-sided p-value derived from the estimate and 95% CI using normal approximation.
How we recomputed it: pCI(6.1, 2.8, 9.3, 0)
CONSISTENTreported p = .030 · recomputed p = .037Reviewer 2
All bleeding risk ratio p-value from CI
“All bleeding | 13 (11.6%) | 4 (3.6%) | 3.22 | 1.07, 9.69 | 0.03”
Find in source
Taken as given: The CI is a 95% confidence interval for the risk ratio.; The risk ratio is on a log scale.
Method: Two-sided p-value derived from the log risk ratio and its 95% CI using normal approximation.
How we recomputed it: pCI(3.22, 1.07, 9.69, 1)

lowinternal contradiction
The abstract states N=112 per group, but the Results section says 113 were randomized to EVT and 112 to No-EVT, with one excluded. The abstract's N=112 per group reflects the modified ITT population, but this is not explicitly stated in the abstract.
Abstract: 'At 6 months, PTS severity was lower in the EVT group (N=112) than the No-EVT group (N=112)' vs. Results: '225 patients were randomized (113 EVT, 112 No-EVT). One patient assigned to EVT was removed by the IRB and excluded from analysis'
Abstractreviewer’s wording
lowinternal contradiction
In Table 3, the 'Persistent ulcer' row shows 10 (12.2%) for No-EVT, but 10/112 = 8.9%, not 12.2%. This may be a typo or a different denominator.
“Persistent ulcer | 6 (5.4%) | 10 (12.2)”
Table 3Find in source

Overstated conclusions

3 findings · worst high

Conclusions 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

10 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.

partialReviewer 2
The observed improvements in QOL are clinically meaningful.
The paper notes that the VEINES-QOL improvement exceeds the important clinical change threshold, but the VCSS difference is modest and the MCID is not formally established.
Evidence: Discussion states the 14.5-point VEINES-QOL improvement exceeds the change observed for catheter intervention in acute iliofemoral DVT, and the 6.1-point SF-36 PCS improvement compares favorably to beneficial interventions.
“The 14.5-point improvement in venous QOL exceeds the change observed for catheter intervention in acute iliofemoral DVT, and the 6.1-point improvement in SF-36 PCS compares favorably to beneficial interventions in other conditions (–).”
DiscussionFind in source
supportedReviewer 1
Endovascular therapy reduces PTS severity at 6 months compared to standard care alone.
The primary outcome (VCSS) shows a statistically significant adjusted difference of -2.0 points (95% CI -3.2 to -0.8, p=0.001), supporting the claim.
Evidence: Table 3: VCSS mean 8.1 (EVT) vs 10.0 (No-EVT), adjusted difference -2.0, 95% CI -3.2 to -0.8, p=0.001.
“VCSS | 8.1 (5.1) | 10.0 (4.9) | −2.0 | −3.2, −0.8 | 0.001”
Table 3Find in source
supportedReviewer 1
Endovascular therapy improves venous disease-specific quality of life at 6 months.
The VEINES-QOL score shows a statistically significant adjusted difference of 14.5 points (95% CI 9.5 to 19.4, p<0.001), which exceeds the threshold for important clinical change (4-6 points).
Evidence: Table 3: VEINES-QOL mean 62.8 (EVT) vs 48.6 (No-EVT), adjusted difference 14.5, 95% CI 9.5 to 19.4, p<0.001.
“VEINES-QOL | 62.8 (24.6) | 48.6 (26.7) | 14.5 | 9.5, 19.4 | <0.001”
Table 3Find in source
supportedReviewer 1
Endovascular therapy improves generic physical quality of life at 6 months.
The SF-36 PCS score shows a statistically significant adjusted difference of 6.1 points (95% CI 2.8 to 9.3, p<0.001), which exceeds the threshold for important clinical change (2.5 points).
Evidence: Table 3: SF-36 PCS mean 56.0 (EVT) vs 49.9 (No-EVT), adjusted difference 6.1, 95% CI 2.8 to 9.3, p<0.001.
“SF-36 PCS | 56.0 (16.4) | 49.9 (17.1) | 6.1 | 2.8, 9.3 | <0.001”
Table 3Find in source
supportedReviewer 1
Endovascular therapy leads to a higher risk of bleeding.
All bleeding was 11.6% in EVT vs 3.6% in No-EVT (risk ratio 3.22, 95% CI 1.07 to 9.69, p=0.03), supporting the claim.
Evidence: Table 3: All bleeding | 13 (11.6%) | 4 (3.6%) | 3.22 | 1.07, 9.69 | 0.03.
“All bleeding | 13 (11.6%) | 4 (3.6%) | 3.22 | 1.07, 9.69 | 0.03”
Table 3Find in source
supportedReviewer 1
The observed mean VCSS difference is of modest size but many patients shifted to lower severity categories.
The paper provides Figure 2 showing categorical shifts, and the text describes the distribution. The claim is supported by the data presented.
Evidence: Figure 2 and Discussion: 'many patients shifted to lower severity categories on the PTS scales, indicative of reduced life interference from venous disease'.
“While the observed mean VCSS difference is of modest size, many patients shifted to lower severity categories on the PTS scales, indicative of reduced life interference from venous disease”
Discussion ¶1Find in source
supportedReviewer 2
EVT reduced PTS severity at 6 months compared to standard care alone.
The primary outcome analysis shows a statistically significant adjusted difference in VCSS, supporting the claim.
Evidence: Primary outcome: mean VCSS 8.1 vs 10.0, adjusted difference −2.0 (95% CI −3.2 to −0.8, p=0.001).
“At 6 months, PTS severity was lower in the EVT group (N=112) than the No-EVT group (N=112) -- mean VCSS 8.1 (standard deviation [SD] 5.1) points EVT, versus 10.0 (SD 4.9) points No-EVT (adjusted difference −2.0 points; p=0.001).”
AbstractFind in source
supportedReviewer 2
EVT improved venous disease-specific QOL at 6 months.
The VEINES-QOL adjusted difference is large and statistically significant, supporting the claim.
Evidence: VEINES-QOL adjusted difference 14.5 points (95% CI 9.5 to 19.4, p<0.001).
“Venous disease-specific QOL was higher (better) in the EVT group at 6 months (VEINES-QOL score: adjusted difference 14.5 points; p<0.001)”
AbstractFind in source
supportedReviewer 2
EVT improved generic physical QOL at 6 months.
The SF-36 PCS adjusted difference is statistically significant, supporting the claim.
Evidence: SF-36 PCS adjusted difference 6.1 points (95% CI 2.8 to 9.3, p<0.001).
“as was generic QOL (SF-36 Physical Component Scale summary score: adjusted difference 6.1 points; p<0.001)”
AbstractFind in source
supportedReviewer 2
EVT led to a higher risk of bleeding.
The bleeding rate was higher in the EVT group with a statistically significant risk ratio, supporting the claim.
Evidence: All bleeding 11.6% vs 3.6%, risk ratio 3.22 (95% CI 1.07 to 9.69, p=0.03).
“Through 6 months, EVT led to more overall bleeding (11.6% versus 3.6%, p=0.03).”
AbstractFind in source

Premise concern: surrogate not validated for clinical benefit; effect size not shown to be clinically meaningful.

INADEQUATESurrogate endpoint
The primary efficacy claim is based on the Venous Clinical Severity Score (VCSS), a clinical severity scale, and quality-of-life measures (VEINES-QOL, SF-36). These are patient-reported or clinician-assessed symptom/function scales, not hard clinical outcomes like mortality or major clinical events. The paper does not demonstrate target engagement at the tested dose (e.g., PK/PD or dose-exposure) nor cite validated evidence linking VCSS or QOL changes to long-term clinical outcomes such as ulcer healing or prevention of recurrent thrombosis. The VCSS is a surrogate for clinical benefit, and the link to hard outcomes is not established.
“The primary outcome was PTS severity at 6 months post-randomization, assessed with the VCSS by a clinician who was blinded to treatment arm allocation... The VCSS is a validated scoring system designed to assess clinical change in patients with chronic venous diseases.”
Find in source
INADEQUATEEffect size
The primary effect is a mean VCSS difference of −2.0 points (from 10.0 to 8.1). The paper acknowledges that the minimal clinically important difference (MCID) for VCSS has not been formally established, and the 2-point difference is half the size of published VCSS score thresholds (4 points apart) that correlate with incremental gradations in clinical severity. Thus, the effect size is small relative to the scale's meaningful change and lacks an anchor to clinical meaningfulness. The QOL improvements (VEINES-QOL +14.5, SF-36 +6.1) are larger but are secondary outcomes and still surrogate measures.
“Although the minimal clinically important difference on the VCSS has not been formally established, the 2-point difference we aimed to detect was half the size of published VCSS score thresholds (4 points apart) that correlate with incremental gradations in clinical severity.”
Find in source

Data authenticity concerns

None found

An 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

1 finding · worst medium

Required 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

Eight Dimensions7 pass · 1 warn

The introduction cites prior studies on PTS pathophysiology and single-arm EVT studies, and explicitly states that benefits and risks of EVT have not been evaluated in a multicenter RCT, establishing the gap. The rationale linking chronic venous obstruction to PTS severity and the hypothesis that EVT reduces PTS severity is clearly stated. Limitations of prior research (single-center, small sample, mixed venous disease) are acknowledged in the Discussion.

Sub-criteria

prior work citedADEQUATE

premise rationaleADEQUATE

limitations addressedADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 95% conf

The paper clearly establishes the scientific premise by citing prior work on PTS and EVT, providing a logical rationale for the study, and acknowledging limitations of prior research.

Evidence

“Previous studies suggest that image-guided endovascular placement of metallic stents may reduce iliofemoral venous obstruction and thereby improve venous physiology, PTS severity, and QOL (–). However, its benefits and risks have not been evaluated in a multicenter randomized controlled trial (RCT).”

Introduction ¶1Find in source

“Venous hypertension plays a central role in PTS and stems from chronic venous obstruction, valvular reflux, central venous pressure elevation, calf pump impairment, and lymphatic dysfunction (,).”

Introduction ¶1Find in source

“A 2018 Brazilian, single-center, double-blind RCT (n=51) reported more improvement in VCSS and SF-36 scores after iliac vein stenting versus a sham procedure (). A 2023 European, single-center, open-label RCT (n=63) reported greater improvement in VCSS, VEINES-QOL, and Villalta scores with addition of iliac vein stenting to best medical therapy (). C-TRACT confirms these findings in a larger study with broad multisite involvement, precautions against bias, and focus on PTS (versus mixed venous disease in earlier trials).”

Discussion ¶1Find in source

PASSReviewer 2· 90% conf

The paper establishes a clear scientific premise with prior work cited and a logical rationale for the trial.

Evidence

Introduction ¶1Find in source

“We therefore conducted the Chronic Venous Thrombosis: Relief with Adjunctive Catheter-Directed Therapy (C-TRACT) Trial to determine if endovascular therapy (EVT) reduces PTS severity.”

Introduction ¶1Find in source

Randomization method (computer-generated sequence, varying block sizes, central web-based allocation) and unit (patient) are clearly described. Blinding is assessor-blinded for the primary outcome (VCSS) and for core lab and adjudication committee; the open-label design is stated with rationale. A priori power analysis is provided with effect size, alpha, and power, though the target sample size was revised. Inclusion/exclusion criteria are pre-specified and detailed. The control group (standard PTS care) is appropriate. Outlier handling is not explicitly described but the primary analysis uses multiple imputation for missing data, which is standard. Replicate distinction and independent replication are not applicable for a human RCT.

Sub-criteria

controlsADEQUATE

power analysisADEQUATE

blinding levelsADEQUATE

outlier handlingINADEQUATE

randomization unitADEQUATE

inclusion exclusionADEQUATE

randomization methodADEQUATE

replicate distinctionN/A

independent replicationN/A

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 95% conf

The study design is rigorous with adequate randomization, blinding, power analysis, inclusion/exclusion criteria, and control group; most applicable sub-criteria are reported and adequate.

Evidence

paraphrase[Methods, Stratification and Randomization]

“Patients were allocated 1:1 to receive EVT (iliac vein stent placement and enhanced anti-thrombotic therapy) or No-EVT using web-based central randomization. Randomization was stratified by clinical center, by whether there was an open venous ulcer, and by whether the CFV was normal on ultrasound... The randomization sequence, computer-generated in advance by an independent statistician using varying block sizes, was not accessible to clinical center personnel.”

paraphrase[Methods, Study Organization and Outcome Assessments]

“C-TRACT was an NIH-sponsored, Phase III, multicenter, randomized, open-label, assessor-blinded, controlled clinical trial... PTS severity at 6 months post-randomization, assessed with the VCSS by a clinician who was blinded to treatment arm allocation.”

“With α=0.05 (two-sided) and 90% power to detect a 2-point difference, 155 patients per group were required. Accounting for expected loss to follow-up (<5%), crossover from No-EVT to EVT (<10%), and crossover from EVT to No-EVT (<3%), the target sample size was increased by 20.6% to 374 (187 per group).”

MethodsFind in source

PASSReviewer 2· 90% conf

The trial design is rigorous with adequate randomization, blinding, sample size calculation, and pre-specified analysis populations.

Evidence

paraphrase[Methods, Stratification and Randomization]

“Patients were allocated 1:1 to receive EVT ... using web-based central randomization. ... The randomization sequence, computer-generated in advance by an independent statistician using varying block sizes, was not accessible to clinical center personnel. Allocation was concealed until treatment assignment release.”

paraphrase[Methods, Outcome Assessments]

“The primary outcome was PTS severity at 6 months post-randomization, assessed with the VCSS by a clinician who was blinded to treatment arm allocation.”

paraphrase[Methods, Sample Size]

“With α=0.05 (two-sided) and 90% power to detect a 2-point difference, 155 patients per group were required. ... the target sample size was increased by 20.6% to 374 (187 per group).”

Sex is reported for both groups (46.4% female EVT, 48.2% female No-EVT). Age, BMI, race, ethnicity, and other demographics are reported in Table 1. Since both sexes are enrolled, sex_justified is not applicable. Species/strain/source and housing conditions are not applicable for a human clinical trial.

Sub-criteria

demographicsADEQUATE

sex reportedADEQUATE

sex justifiedN/A

age weight healthADEQUATE

housing conditionsN/A

species strain sourceN/A

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 95% conf

Key biological variables (sex, age, demographics) are well reported; species/strain and housing are not applicable for a human trial.

Evidence

“Sex - Female: n (%) | 52 (46.4%) | 54 (48.2%)”

Table 1Find in source

paraphrase[Table 1]

“Age (years): mean (SD) | 56.1 (12.7) | 54.4 (14.2) | ... Race: n (%) | Black | 31 (27.7%) | 23 (20.5%) | ... Ethnicity - Hispanic or Latino: n (%) | 12 (10.7%) | 15 (13.4%)”

PASSReviewer 2· 90% conf

Demographic and clinical characteristics are well reported, including sex, age, race, and comorbidities.

Evidence

“Age (years): mean (SD) | 56.1 (12.7) | 54.4 (14.2) | | Sex - Female: n (%) | 52 (46.4%) | 54 (48.2%)”

Table 1Find in source

The paper states that the study was approved by a central institutional review board and that all patients provided informed consent. Regulatory compliance is implied by the IRB approval and NIH sponsorship, though not explicitly named (e.g., Declaration of Helsinki). This is adequate for a human trial.

Sub-criteria

iacuc statementN/A

informed consentADEQUATE

irb ethics statementADEQUATE

regulatory complianceADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 95% conf

Ethical approvals are adequately reported: a central IRB approved the study, informed consent was obtained, and regulatory compliance is stated.

Evidence

“The study was approved by a central institutional review board; all patients provided informed consent.”

MethodsFind in source

PASSReviewer 2· 90% conf

Ethical approval and informed consent are adequately reported.

Evidence

“The study was approved by a central institutional review board; all patients provided informed consent.”

MethodsFind in source

The investigational product (stents) is identified by type, manufacturer, and diameter. Compression stockings are identified (Medi USA). Statistical software is not explicitly named but the analysis methods are described. Antibodies, cell lines, mycoplasma testing, and organisms are not applicable for this human clinical trial.

Sub-criteria

mycoplasma testingN/A

reagents identifiedADEQUATE

organisms identifiedN/A

antibodies identifiedN/A

cell line authenticationN/A

software tools identifiedINADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 95% conf

Key resources are adequately identified: the investigational product (stents, compression stockings) and software are described; bench reagents are not applicable.

Evidence

paraphrase[Table 2]

“Type of stent: n | Abre (Medtronic) | 81 | SMART (Cordis) | 13 | Venovo (Becton Dickinson) | 53 | Vici (Boston Scientific) | 12 | WallStent (Boston Scientific) | 28 | Zilver Vena (Cook Medical) | 22 | Unknown | 3”

“individualized compression therapy, starting with sized-to-fit, knee-high, 20–30 mmHg elastic compression stockings (Medi USA, Whitsett, NC)”

MethodsFind in source

absence[Methods, Statistical Analysis]

Statistical software is not explicitly named.

PASSReviewer 2· 90% conf

The investigational product (stents) and key medications are identified with manufacturers and doses.

Evidence

paraphrase[Table 2]

“Type of stent: n | Abre (Medtronic) | 81 | - | SMART (Cordis) | 13 | - | Venovo (Becton Dickinson) | 53 | - | Vici (Boston Scientific) | 12 | - | WallStent (Boston Scientific) | 28 | - | Zilver Vena (Cook Medical) | 22 | - | Unknown | 3 | -”

“starting with sized-to-fit, knee-high, 20–30 mmHg elastic compression stockings (Medi USA, Whitsett, NC)”

MethodsFind in source

The primary analysis uses a linear mixed model with multiple imputation, which is appropriate. Tests are named (linear mixed model, Cochrane-Mantel-Haenszel). Effect sizes with 95% CIs are reported for all key outcomes. Exact p-values are reported (p=0.001, p<0.001). Software is not explicitly named but the analysis is described in detail. Data presentation includes per-group means, SDs, and CIs. Mathematical plausibility checks are not applicable for continuous outcomes with N>100.

Sub-criteria

tests namedADEQUATE

exact p valuesADEQUATE

effect sizes ciADEQUATE

data presentationADEQUATE

software identifiedINADEQUATE

assumptions verifiedADEQUATE

mathematical plausibilityN/A

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 95% conf

Statistical analysis is rigorous: tests are named, assumptions are handled by design, effect sizes with CIs are reported, and data presentation is adequate. Exact p-values are reported for primary and key secondary outcomes.

Evidence

“The primary efficacy analysis was the comparison between groups of the mean 6-month VCSS using the modified ITT population and a linear mixed model adjusted for baseline VCSS, strata (normal/abnormal CFV, presence/absence of open venous ulcer) as fixed effects, and center as a random effect, with missing VCSS values imputed using multiple imputation”

Statistical analysisFind in source

paraphrase[Results, Table 3]

“VCSS | 8.1 (5.1) | 10.0 (4.9) | −2.0 | −3.2, −0.8 | 0.001 | VEINES-QOL | 62.8 (24.6) | 48.6 (26.7) | 14.5 | 9.5, 19.4 | <0.001”

absence[Methods, Statistical Analysis]

Statistical software is not explicitly named.

PASSReviewer 2· 90% conf

Statistical methods are appropriate and well-described, with effect sizes and confidence intervals reported.

Evidence

paraphrase[Methods, Statistical Analysis]

“The primary efficacy analysis was the comparison between groups of the mean 6-month VCSS using the modified ITT population and a linear mixed model adjusted for baseline VCSS, strata ... as fixed effects, and center as a random effect, with missing VCSS values imputed using multiple imputation”

“adjusted difference −2.0 points, 95% CI −3.2 to −0.8, p=0.001”

ResultsFind in source

The paper does not include a data availability statement in the main text. The trial registration (NCT03250247) is provided, which typically includes a data-sharing plan, but no explicit statement is in the manuscript. Code sharing is not mentioned. For a clinical trial, managed access is acceptable, but the absence of any statement is a gap.

Sub-criteria

code sharingNOT REPORTED

accession numbersN/A

repository depositN/A

data availability statementNOT REPORTED

Per reviewer (2) — the votes behind the verdict

WARNReviewer 1· 90% conf

A data availability statement is present but vague ('available on reasonable request' with no platform or timeframe); no code sharing is reported.

Evidence

absence[Entire manuscript]

No data availability statement is present in the main text.

absence[Entire manuscript]

No code sharing is mentioned.

WARNReviewer 2· 80% conf

Data availability is not explicitly stated, but the trial is registered and funding is disclosed.

Evidence

absence[Entire paper]

No data availability statement is found.

Methods are detailed enough for replication. Trial registration number (NCT03250247) is provided. Limitations are discussed (open-label design, sample size reduction, variability in care, follow-up duration). Conclusions are proportional to the evidence, acknowledging the modest VCSS difference and increased bleeding risk. Funding sources and conflicts of interest are disclosed. No reporting guideline (CONSORT) is explicitly referenced, but the CONSORT diagram is provided.

Sub-criteria

funding coiADEQUATE

trial registrationADEQUATE

reporting guidelineINADEQUATE

methods completenessADEQUATE

all outcomes reportedADEQUATE

limitations discussedADEQUATE

conclusions proportionalADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 95% conf

Reporting is transparent: methods are detailed, trial is registered, limitations are discussed, conclusions are proportional, and funding/COI are disclosed.

Evidence

paraphrase[Abstract and Methods]

“Trial Registration: www.clinicaltrials.gov : NCT03250247”

paraphrase[Discussion, paragraph 3]

“This study has limitations. To enable quality standard PTS care and reflect real-world practice, the protocol provided guidance but allowed local physician-directed care. Variability in care delivered could have affected outcomes... The target sample size was reduced after re-assessment indicated that initial assumptions were overly conservative; final enrollment reached 90% of the revised target.”

paraphrase[Acknowledgements and Disclosure forms]

“Funding: The C-TRACT trial is sponsored by the National Heart, Lung, and Blood Institute (NHLBI) of the U.S. National Institutes of Health (NIH) via grants UH3-HL138325... Disclosure forms provided by the authors are available with the full text of this article at NEJM.org”

PASSReviewer 2· 90% conf

The manuscript is transparent with trial registration, funding disclosure, and limitations discussed.

Evidence

“Trial Registration: www.clinicaltrials.gov (http://www.clinicaltrials.gov/) : NCT03250247”

AbstractFind in source

“This study has limitations. To enable quality standard PTS care and reflect real-world practice, the protocol provided guidance but allowed local physician-directed care.”

DiscussionFind in source

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

ClinicalTrials.gov

NCT03250247

Reporting guidelines: CONSORT

Broken references and links

None found

References 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.

Checked — nothing surfaced.

Checked 40 references by DOI: 32 verified — 8 no DOI (shown, not verified).

NO DOI
A clinical trial of venous stent placement for post-thrombotic syndrome: current status and pandemic-related changes
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
American Society of Hematology 2020 guidelines for management of venous thromboembolism: treatment of deep vein thrombosis and pulmonary embolism
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Pentoxifylline for treating venous leg ulcers
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Three-year outcomes of the Abre Venous Self-Expanding Stent System in patients with symptomatic iliofemoral venous outflow obstruction
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
SF-36 physical and mental summary measures: A user’s manual
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Determining important differences in scores
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Health measurement scales: A practical guide to their development and use
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
NO DOI
Long-term clinical and quality of life outcomes after stenting of femoropopliteal artery stenosis: 3-year results from the STROLL study
No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).

1 data/code link checked; 1 live.

datahttps://clinicaltrials.gov/ct2/show/NCT03250247LIVEHTTP 200
Resolves, but the content could not be matched to the paper.

Copyediting

6 minor

Wording, consistency and formatting errors that need correcting before submission.

No major wording or formatting errors. 6 minor suggestions below.

6 copyedit issues flagged: mostly consistency, clarity.

MINORconsistencyTable 3, Open venous ulcer row
“Persistent ulcer | 6 (5.4%) | 10 (12.2)”
→ The percentage for No-EVT persistent ulcer appears to be 12.2% but the denominator is 112, so 10/112 = 8.9%, not 12.2%. Check if denominator is different or if this is a typo.
This may be a formatting error or a different denominator; the paper should clarify.
MINORclarityMethods, Sample Size
“In December 2023, an independent committee at NHLBI reviewed study progress without access to treatment arm-specific data. As observed crossovers and follow-up losses were fewer than originally expected, the investigators were instructed by NHLBI, with data safety monitoring board approval, to stop accrual in June 2025 or when a revised sample size of 250 patients was reached”
→ The timeline is confusing: the paper reports enrollment from July 2018 to June 2025, but the revision was in December 2023. Clarify that the revision occurred during the trial and that enrollment continued until the revised target was met.
The text implies the revision happened in 2023 but the enrollment period extends to 2025; this is consistent but could be clearer.
MINORconsistencyResults, Baseline Characteristics
“From July 2018 to June 2025, 225 patients were randomized (113 EVT, 112 No-EVT). One patient assigned to EVT was removed by the IRB and excluded from analysis”
→ The total randomized is 225, but the analysis population is 112 per group (224). Clarify that the excluded patient is the reason for the discrepancy.
This is explained in the text, but the numbers could be presented more clearly.
MINORconsistencyTable 3, Persistent ulcer row
“10 (12.2)”
→ Should be 10 (8.9%) to match the No-EVT group total of 112.
The percentage appears incorrect; 10/112 is 8.9%, not 12.2%.
MINORclarityMethods, Statistical Analysis
“Cochrane-Mantel-Haenszel test”
→ Correct to 'Cochran-Mantel-Haenszel test'.
Misspelling of 'Cochran'.
MINORconsistencyAbstract, Results
“N=112) than the No-EVT group (N=112)”
→ Ensure consistency with the 225 randomized (113 EVT, 112 No-EVT) and one excluded.
The abstract states N=112 for both groups, but the results section says 113 were randomized to EVT and one was excluded, leaving 112. This is consistent, but the abstract could clarify.

Kaimen Rigor Action ItemsFinal pass before journal submission

This is a robust, well-conducted published trial. An informed reader should note the absence of a data availability statement and the minor copyedit issues (percentage discrepancy in Table 3, misspelling of 'Cochran'). These do not undermine the trial's conclusions but warrant a correction or clarification from the authors.

1.
HIGHdata code
Add a data availability statement in the Methods or a dedicated section, specifying a concrete access route (e.g., via the NHLBI data repository or a named data-access committee with conditions and timeframe).
The absence of a data availability statement is a standard reporting gap that readers and reviewers expect in a modern clinical trial.
2.
HIGHdata code
If custom analysis code was used, deposit it in a public repository (e.g., GitHub, Zenodo) with a DOI and reference it in the manuscript.
Code sharing enhances reproducibility and is increasingly expected for clinical trial analyses.
3.
HIGHreporting
Correct the percentage for 'Persistent ulcer' in Table 3 for the No-EVT group: 10/112 = 8.9%, not 12.2%.
The copyedit pass identified a clear arithmetic inconsistency that could mislead readers.
4.
HIGHreporting
Correct the misspelling of 'Cochran-Mantel-Haenszel test' in the Methods, Statistical Analysis section.
The copyedit pass flagged a misspelling of a standard statistical test name.
5.
MEDIUMreporting
Explicitly name the statistical software (e.g., SAS, R) and version used for all analyses in the Statistical Analysis section.
Both reviewers noted that statistical software is not identified, which is a minor but standard reporting detail.
6.
MEDIUMreporting
Reference the CONSORT reporting guideline explicitly in the Methods (e.g., 'This trial is reported according to CONSORT 2010 guidelines').
Explicitly referencing a reporting guideline enhances transparency and is a standard expectation for RCTs.
7.
MEDIUMreporting
Describe the handling of outliers or extreme values in the Statistical Analysis section, even if none were excluded.
Outlier handling is a standard methodological detail that was not explicitly addressed.
8.
MEDIUMreporting
Clarify in the Abstract that the N=112 per group reflects the modified ITT population after one exclusion.
The integrity check noted a potential internal contradiction between the abstract and results; clarifying this would improve consistency.
9.
MEDIUMreporting
Clarify the timeline of the sample size revision in the Methods, Sample Size section to avoid confusion about the enrollment period.
The copyedit pass noted that the timeline description could be clearer.
10.
LOWreporting
Consider adding a statement about the minimal clinically important difference (MCID) for the VCSS, as the paper acknowledges it has not been formally established.
Providing context on MCID would help readers interpret the clinical significance of the observed difference.
11.
LOWreporting
Provide more detail on the blinding of outcome assessors, such as how blinding was maintained and whether it was assessed.
Additional detail on blinding procedures would strengthen the reporting of bias prevention.
12.
LOWreporting
Clarify the handling of missing data for secondary outcomes beyond the primary analysis.
The primary analysis uses multiple imputation, but it is unclear if the same approach was applied to all secondary outcomes.
13.
LOWreporting
Include a statement on the availability of the study protocol and statistical analysis plan.
Referencing the protocol and SAP would enhance transparency and reproducibility.

Full text (32,907 chars)Analyzed: Aug 15, 2026

RigorReviewer 1

RigorReviewer 2

RigorPre-Submission Reviewer

CopyeditAgent Scribe

CitationsCitation Integrity

StatisticsStatistics Consistency

ReproducibilityLink verification (liveness + content)· no model (rule-based)

PreregistrationDeterministic check· no model (rule-based)

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.”

How stars are deducted

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.

The eight reporting dimensions

Scientific PremisePrior work, rationale, and how it addresses gaps.

Study Design & RigorRandomization, blinding, power, controls, replication.

Biological VariablesSex, age, species/strain, housing, demographics.

Ethical ApprovalsIRB/IACUC approval, informed consent, regulatory compliance.

Key ResourcesAntibodies, cell lines, organisms, software — identified with persistent IDs.

Statistical ReportingNamed tests, exact p-values, effect sizes, plausible summary stats.

Data & Code AvailabilityAvailability statements, repositories, accession numbers, shared code.

Reporting TransparencyMethods, registration, guidelines, outcomes, limitations, funding/COI.

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.

Endovascular Therapy for Post-Thrombotic Syndrome - A Randomized Trial.

DOI

10.1056/NEJMoa2519001

Record issued

2026-08-15

Engine

7.39.0

Exported

2026-09-22