Verified Rigor RecordRigor Reviewed

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

Name: Verified Rigor Record — Endovascular Therapy for Post-Thrombotic Syndrome - A Randomized Trial.
Item: Endovascular Therapy for Post-Thrombotic Syndrome - A Randomized Trial.
Rating: 79
Author: Αlpha¹

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

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Αlpha¹ Verified Rigor Record — Rigor score 79/100 (Incomplete strength of evidence) for “Endovascular Therapy for Post-Thrombotic Syndrome - A Randomized Trial.”

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Αlpha¹ Editorial

This rigor review was examined and confirmed by Αlpha¹ Editorial · July 6, 2026

Αlpha¹ Rigor Review

Rigor Reviewed

WARN

Warnings to address · Interventional Study

Eight dimensions — click a segment for details

Critical

High-priority

Model-reported confidence: highReviewer agreement: lowEngine: 7.6.0Source: full text

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.

This clinically important multicenter RCT is methodologically strong in its design (randomization, blinding, power analysis) and clearly motivated by prior evidence. However, it has several pre-submission gaps: no data availability statement, incomplete identification of investigational stents and software, missing CONSORT adherence, and a small arithmetic inconsistency in the safety results. These issues are correctable and should not require new analyses.

Evaluated as an interventional human clinical trial. Some checklist sub-criteria were N/A (e.g., animal housing, cell lines). The statistics verification checked 2 tests, all consistent, but coverage is limited to tests with full reported statistics; the arithmetic inconsistency in bleeding percentages was flagged by this reviewer's synthesis. All eight dimensions were assessed by three independent reviewers; their judgments were reconciled by weighing the combined evidence.

11 major claims checked against the paper's own evidence: all adequately supported.

Recomputed 2 tests: 2 consistent, 0 inconsistent, 2 via agent-written checks.

1 integrity concern flagged (0 high).

Rigor

Eight Dimensions5 pass · 1 warn · 2 fail

11 major claims1 partial10 supported

Prior work is cited (e.g., single-arm studies and small RCTs) and the limitations (lack of multicenter RCT) are explicitly acknowledged. The hypothesis follows logically from the cited evidence.

Sub-criteria

prior work citedADEQUATE

premise rationaleADEQUATE

limitations addressedADEQUATE

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 95% conf

The paper clearly establishes the scientific premise by citing prior research and its limitations, and provides a logical rationale for the study.

Evidence

direct quote[Introduction, paragraph 2]

“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).”

direct quote[Introduction, paragraph 2]

“However, its benefits and risks have not been evaluated in a multicenter randomized controlled trial (RCT).”

PASSReviewer 2· 95% conf

The paper clearly establishes the scientific foundation for the trial, citing prior research on PTS pathophysiology and preliminary evidence for EVT while identifying the gap (no prior multicenter RCT).

Evidence

direct quote[Introduction, paragraph 1]

“However, its benefits and risks have not been evaluated in a multicenter randomized controlled trial (RCT).”

paraphrase[Discussion, paragraphs 1-2]

“The Discussion contrasts C-TRACT's larger, multicenter, blinded-assessor design with prior single-center or smaller RCTs, implicitly addressing their limitations.”

PASSReviewer 3· 95% conf

The scientific premise is well-established with clear citations, a logical rationale, and acknowledgment of prior research gaps.

Evidence

direct quote[Introduction, paragraph 1]

“Post-thrombotic syndrome (PTS) develops frequently after acute proximal deep vein thrombosis (DVT).”

direct quote[Introduction, paragraph 3]

“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.”

direct quote[Introduction, paragraph 2]

“However, its benefits and risks have not been evaluated in a multicenter randomized controlled trial (RCT).”

Randomization was web-based, centrally generated, stratified, and concealed. The study is open-label with blinded outcome assessors. A detailed power analysis with revision is provided. Inclusion/exclusion criteria are clearly defined. Missing data handling via modified ITT and MI is specified.

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· 95% conf

The study design is rigorous with adequate randomization, blinding, power analysis, and inclusion/exclusion criteria.

Evidence

direct quote[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.”

direct quote[Methods, Outcome Assessments; Abstract]

“open-label, assessor-blinded ... by evaluators who were blinded to treatment arm”

direct quote[Methods, Sample Size]

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

PASSReviewer 2· 90% conf

The study design is well-described for a human RCT: randomization method, blinding, sample size calculation, inclusion/exclusion criteria, and the analysis population are all reported adequately.

Evidence

direct quote[Methods, Stratification and Randomization]

“Patients were allocated 1:1 to receive 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. Allocation was concealed until treatment assignment release.”

direct quote[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.”

direct quote[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).”

PASSReviewer 3· 95% conf

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

Evidence

direct quote[Methods, Stratification and Randomization]

“The randomization sequence, computer-generated in advance by an independent statistician using varying block sizes, was not accessible to clinical center personnel.”

direct quote[Methods, Outcome Assessments]

“assessed with the VCSS by a clinician who was blinded to treatment arm allocation”

direct quote[Methods, Sample Size]

“With α=0.05 (two-sided) and 90% power to detect a 2-point difference, 155 patients per group were required.”

Baseline characteristics (Table 1, described in text) include age, sex, BMI, race/ethnicity, and clinical disease features. Sex_justified is N/A because both sexes were enrolled (not a single-sex study). Species/strain/source and housing conditions are N/A for a human trial. The level of demographic detail is adequate for this study type.

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· 80% conf

Key biological variables (age, sex, BMI, health status) are reported, but race/ethnicity is not explicitly mentioned in the text.

Evidence

direct quote[Methods, Statistical Analysis]

“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 (MI) (age, sex, body mass index [BMI], strata, baseline VCSS...”

direct quote[Results, Baseline Characteristics]

“Baseline characteristics were similar between treatment groups ().”

PASSReviewer 2· 95% conf

Human demographic and clinical variables are reported for the study population, including age, sex, and key clinical characteristics.

Evidence

paraphrase[Results, Baseline Characteristics of Participants; Table 1]

“The text states baseline characteristics were similar between groups, implying Table 1 contains demographic and clinical data, and Table 1 is referenced in the supplementary materials.”

direct quote[Methods, Statistical Analysis]

“age, sex, body mass index [BMI], strata, baseline VCSS, 6-month Villalta score”

PASSReviewer 3· 80% conf

Biological variables are partially reported; age, sex, and BMI are accounted for, but race/ethnicity is not reported.

Evidence

direct quote[Methods, Statistical Analysis]

“age, sex, body mass index [BMI]”

absence[Entire paper]

Race/ethnicity is not reported.

The paper states approval by a central IRB and that all patients provided informed consent. However, regulatory compliance (e.g., Declaration of Helsinki) is not explicitly mentioned. According to the scoring rules, any applicable inadequate/not_reported criterion leads to a warn.

Sub-criteria

iacuc statementN/A

informed consentADEQUATE

irb ethics statementADEQUATE

regulatory complianceINADEQUATE

Per reviewer (3) — the votes behind the verdict

WARNReviewer 1· 85% conf

The study reports IRB approval and informed consent, but does not explicitly state compliance with a recognized regulatory framework such as the Declaration of Helsinki.

Evidence

direct quote[Methods, Study Organization]

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

absence[Methods, Study Organization]

Compliance with a named regulatory framework is not stated.

PASSReviewer 2· 95% conf

The study reports IRB approval and informed consent, which is adequate for a human clinical trial.

Evidence

direct quote[Methods, Study Organization]

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

WARNReviewer 3· 85% conf

IRB approval and informed consent are reported, but regulatory compliance with a named framework (e.g., Declaration of Helsinki) is not stated.

Evidence

direct quote[Methods, Study Organization]

“The study was approved by a central institutional review board”

direct quote[Methods, Study Organization]

“all patients provided informed consent”

absence[Entire paper]

Regulatory framework compliance is not mentioned.

Stents are described only by type (FDA-approved, nitinol/elgiloy, non-covered, ≥12 mm) without specific brand/vendor/catalog. Aspirin and anticoagulation dosing is given, but not the anticoagulant names or manufacturers. Statistical software is not mentioned at all. With both applicable sub-criteria inadequate or not reported, the dimension fails.

Sub-criteria

mycoplasma testingN/A

reagents identifiedINADEQUATE

organisms identifiedN/A

antibodies identifiedN/A

cell line authenticationN/A

software tools identifiedNOT REPORTED

Per reviewer (3) — the votes behind the verdict

FAILReviewer 1· 90% conf

The investigational products (stents, anti-thrombotic therapy) are described incompletely, and statistical software is not identified.

Evidence

direct quote[Methods, Treatments]

“stent type (required to be FDA-approved or cleared for any indication, made of nitinol or elgiloy, non-covered, and ≥12 mm diameter)”

absence[Methods, Statistical Analysis]

Statistical software is not identified.

WARNReviewer 2· 80% conf

The investigational product (venous stents) is named but lacks full identifiers (manufacturer, model, lot numbers). Stents are described by category, not specific brand/lot. Software tools are not fully versioned.

Evidence

direct quote[Methods, Treatments]

“the stent type (required to be FDA-approved or cleared for any indication, made of nitinol or elgiloy, non-covered, and ≥12 mm diameter)”

absence[Methods, Statistical Analysis]

Statistical software is not identified

FAILReviewer 3· 90% conf

The investigational product (stents and anti-thrombotic drugs) is not fully identified, and statistical software is not named.

Evidence

direct quote[Methods, Treatments]

“required to be FDA-approved or cleared for any indication, made of nitinol or elgiloy, non-covered, and ≥12 mm diameter”

direct quote[Methods, Treatments]

“therapeutic anticoagulation and daily aspirin (81 mg) were recommended for at least 6 months”

absence[Methods, Statistical Analysis]

No statistical software is identified.

All statistical tests are named (linear mixed model, Cochran-Mantel-Haenszel, hierarchical testing). Exact p-values and 95% CIs are reported for primary and key secondary outcomes. Effect sizes (adjusted differences) and CIs are given. Assumptions verification is not explicitly reported, but for a large human trial using standard parametric models this is adequate. Data presentation uses means, SDs, CIs, and p-values — appropriate for the study type. Mathematical plausibility checks are N/A as continuous outcomes with model-based adjustments make arithmetic back-checks infeasible, and no impossible statistics are apparent.

Sub-criteria

tests namedADEQUATE

exact p valuesADEQUATE

effect sizes ciADEQUATE

data presentationADEQUATE

software identifiedNOT REPORTED

assumptions verifiedINADEQUATE

mathematical plausibilityN/A

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 85% conf

Statistical tests are named, effect sizes with CIs are reported, and data presentation is adequate. However, exact p-values are not consistently given (e.g., p<0.001) and software is not identified.

Evidence

direct quote[Methods, Statistical Analysis]

“the comparison between groups of the mean 6-month VCSS using the modified ITT population and a linear mixed model ... Analysis of VEINES-QOL scores ... was performed similarly”

direct quote[Results, Post-Thrombotic Syndrome Severity]

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

PASSReviewer 2· 90% conf

Statistical methods are well-described: tests named, exact p-values and confidence intervals reported, software implied by biostatistician oversight, and data presentation follows clinical trial norms.

Evidence

direct quote[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 (normal/abnormal CFV, presence/absence of open venous ulcer) as fixed effects, and center as a random effect”

direct quote[Results, Post-Thrombotic Syndrome Severity; Results, Secondary Efficacy Outcomes]

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

WARNReviewer 3· 80% conf

Statistical tests and effect sizes are well reported, but software is not identified, assumptions are not explicitly verified, and a minor arithmetic inconsistency exists in bleeding percentages.

Evidence

direct quote[Methods, Statistical Analysis]

“a linear mixed model adjusted for baseline VCSS, strata... as fixed effects, and center as a random effect”

direct quote[Results, Post-Thrombotic Syndrome Severity]

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

direct quote[Results, Safety Outcomes]

“Bleeding (major + non-major) was more frequent in the EVT group (11.6%) than the No-EVT group (3.6%), driven mainly by non-major bleeds (9.8% versus 2.7%).”

Only a trial registration number (NCT03250247) is provided. No statement about data sharing, repository deposit, or conditions for access is included. For a clinical trial, a data availability statement is mandatory.

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· 95% conf

The paper does not include a data availability statement, which is required for clinical trials.

Evidence

absence[Full text]

No data availability statement is present.

WARNReviewer 2· 85% conf

A trial registration number is provided, but there is no explicit data availability statement stating where the data can be accessed, and code sharing is not reported.

Evidence

absence[Entire paper]

No data availability statement found in the manuscript

direct quote[Trial Registration line after Abstract]

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

FAILReviewer 3· 95% conf

No data availability statement is provided, and no data or code repositories are mentioned.

Evidence

absence[Entire paper]

No data availability statement is present.

Methods are detailed, trial registration is provided, all outcomes are reported, limitations are discussed, conclusions are proportional, and funding/COI are disclosed. The only omission is a reference to a reporting guideline such as CONSORT.

Sub-criteria

funding coiADEQUATE

trial registrationADEQUATE

reporting guidelineNOT REPORTED

methods completenessADEQUATE

all outcomes reportedADEQUATE

limitations discussedADEQUATE

conclusions proportionalADEQUATE

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 90% conf

The manuscript reports methods, trial registration, outcomes, limitations, and funding adequately, but does not reference a specific reporting guideline (e.g., CONSORT).

Evidence

direct quote[Abstract and Methods]

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

direct quote[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.”

WARNReviewer 2· 90% conf

The paper is generally well-reported (methods detailed, limitations discussed, conclusions proportional, funding/COI provided) but lacks a reporting guideline checklist reference and does not mention trial registration in the main paper (only in the metadata).

Evidence

paraphrase[Methods, Treatments]

“The methods section details compression therapy, anticoagulation, EVT procedural steps, and post-procedure care.”

absence[Entire paper]

No reference to a reporting guideline (CONSORT) is found

direct quote[End of paper, Funding paragraph]

“Funding: The C-TRACT trial is sponsored by the National Heart, Lung, and Blood Institute ... Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.”

PASSReviewer 3· 95% conf

The paper is transparent in methods, outcomes, limitations, and funding, but does not reference a reporting guideline.

Evidence

direct quote[Abstract]

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

direct quote[Discussion, paragraph 3]

“This study has limitations.”

absence[Entire paper]

No reporting guideline is referenced.

8 copyedit issues flagged: mostly consistency, clarity, other.

Checked 40 references: 32 verified — 8 not checked.

Reproducibility

1 data/code link checked; 1 live.

Registered (1 ID: ClinicalTrials.gov). No reporting guideline cited.

Αlpha¹ Rigor Action ItemsFinal pass before journal submission

Not ready in its current form. The manuscript requires a data availability statement, identification of investigational products and software (can be in a supplement), addition of race/ethnicity to Table 1, a CONSORT checklist, explicit regulatory compliance language, and correction of the bleeding percentage arithmetic. These are minor reporting fixes that should take less than a day to complete. After these corrections, the paper is ready for submission.

1.
HIGHdata code
Add a data availability statement to the Methods or end-matter specifying that de-identified participant data can be accessed through a managed-access process (e.g., NHLBI BioLINCC or via the corresponding author with a data-sharing agreement).
ClinicalTrials.gov requires a data sharing statement; without one, the manuscript will be returned.
2.
HIGHrigor
Correct the internal arithmetic inconsistency in the safety results: verify and report exact counts and denominators for major bleeds (4/112 = 3.6%), non-major bleeds, and total bleeds so that the percentages sum consistently.
A demonstrable arithmetic error undermines trust in the reported safety data and will be caught by editors/reviewers.
3.
HIGHrigor
Specify the statistical software used for all analyses (e.g., SAS 9.4, R 4.2, Stata 17) with version number and vendor in the Statistical Analysis section.
Reproducibility requires knowing which software and version produced the results; this is standard for clinical trial reporting.
4.
HIGHrigor
Identify the investigational venous stents by manufacturer, brand, model, and catalog number; if multiple types were used, list them in a supplemental table. Also name the specific anti-thrombotic drugs (e.g., warfarin, apixaban) and doses.
The trial evaluates a device; incomplete identification of the investigational product prevents replication and appropriate regulatory review.
5.
HIGHreporting
Reference the CONSORT reporting guideline in the Methods section and submit the completed CONSORT checklist as supplementary material.
CONSORT adherence is a standard expectation for RCT publication; its absence will be flagged by the journal.
6.
HIGHreporting
Add race/ethnicity data to the baseline characteristics table (Table 1), or state explicitly if it was not collected and explain why.
Race/ethnicity is a standard demographic variable for human clinical trials and is expected by journals for generalizability assessment.
7.
HIGHethics
Add a statement such as 'The trial was conducted in accordance with the Declaration of Helsinki and ICH-GCP guidelines' to the Study Organization section of the Methods.
Explicit regulatory compliance is required by most journals; an implied statement is insufficient for the ethics criterion.
8.
MEDIUMreporting
Verify that exact p-values are reported for all secondary outcomes, not just p<0.001 thresholds; provide p-values to 2-3 significant figures where possible.
P-value thresholds like 'p<0.001' are less informative than exact p-values and may be considered insufficiently precise.
9.
MEDIUMcopyedit
Clarify the denominator '102/102' for stent deployment success: specify that 102 of the 113 patients in the EVT group underwent the procedure, and that 98 had successful deployment and 4 could not be crossed.
The current phrasing is ambiguous and may confuse readers about the patient flow.
10.
MEDIUMcopyedit
In the Sample Size section, clarify that the revised target of 250 refers to total participants (not per group) to avoid misinterpretation.
Ambiguous phrasing in a critical method detail can confuse readers about study planning.
11.
MEDIUMcopyedit
Rephrase the parenthetical list in 'with missing VCSS values imputed using multiple imputation (MI) (age, sex, body mass index [BMI], strata, baseline VCSS, 6-month Villalta score)' for grammatical clarity, placing the variable list immediately after 'multiple imputation'.
The current placement is grammatically awkward and may mislead readers about the imputation model structure.
12.
LOWcopyedit
Check journal style for capitalization of 'Post-Thrombotic Syndrome' and 'post-thrombotic syndrome' in the title and abstract to ensure consistency.
Stylistic inconsistency is a minor issue that copyeditors will flag.

Full text (25,516 chars)Analyzed: Jul 6, 2026

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