Rigor Reviewed

Rigor-Reviewed Manuscript

Anti-inflammatory therapy with low-dose IL-2 in acute coronary syndromes: a randomized phase 2 trial.

Name: Αlpha¹ Rigor Record — Anti-inflammatory therapy with low-dose IL-2 in acute coronary syndromes: a randomized phase 2 trial.
Item: Anti-inflammatory therapy with low-dose IL-2 in acute coronary syndromes: a randomized phase 2 trial.
Rating: 96
Author: Αlpha¹

Sriranjan-Rothwell RS, Zhao TX, Hoole SP, Bond SJ, Tarkin JM, Brubert J, Hubsch A, Helmy J, Bumanlag-Amis E, Jalaludeen N, Templin H, Jiang W, Tedgui A, Zhao X, Nus M, Warnes V, Krishnan U, O'Brien JW, Wall C, Rudd JHF, Cheriyan J, Mallat Z, IVORY investigators

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Αlpha¹ Rigor Review — 3★ (Adequate), 0 critical, 7 high issues for “Anti-inflammatory therapy with low-dose IL-2 in acute coronary syndromes: a randomized phase 2 trial.”

Links back to this Rigor Record.

Αlpha¹ Editorial

This rigor review was examined and confirmed by Αlpha¹ Editorial · August 10, 2026

Αlpha¹ Rigor Review

Rigor Reviewed

3 / 5

Adequate — real issues to address

Interventional Study

Critical

High-priority

How this rating was calculated▸

Started at 5★ — deductions

IntegrityIntegrity concern ×4−2★

Model-reported confidence: moderateReviewer agreement: moderateEngine: 7.29.0Source: full text

Problems surfaced4 types

Numerical inconsistencies1

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

Overstated conclusions1

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.

Conclusions only partially backed by the presented evidenceAssessed

Data authenticity concerns1

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.

Other integrity concernAssessed

Copyediting1

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

Wording or formatting errors that need correctingAssessed

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 phase 2 randomized double-blind placebo-controlled trial of low-dose IL-2 in acute coronary syndromes is well designed and transparently reported: randomization, blinding, power analysis, ethics approvals, and the main trial registration are all solid, and the primary result is reported with exact p-values and CIs consistent with the independent recomputation. The main weaknesses are reporting/reproducibility gaps — the investigational IL-2 source and software version are not stated, no analysis code is shared, and there is an internal inconsistency in the IVORY-FINALE registration statement plus an Abstract/Table 1 sex-ratio discrepancy — none of which invalidates the primary IVORY findings but all of which warrant correction.

Three independent reviewer runs from the same model were synthesized; they converged on 6 of 8 dimensions and diverged on key resources and data code availability, where I weighed the more rigorous positions (missing drug source; absent code sharing) against the majority pass and landed on warn. The statistics component machine-checked only 6 tests (those with test statistic + df or estimate + CI); the remaining analyses are unverified, not confirmed. The citation component found 0 retracted and 0 not-found references among 50 checked.

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

Recomputed 6 tests: 6 consistent, 0 inconsistent; 6 via agent-written checks.

4 integrity concerns flagged (1 high).

Reporting

Eight Dimensions8 pass

The paper cites extensive prior research on Treg cells in ACS, the anti-inflammatory effects of IL-2, and limitations of current therapies (e.g., colchicine ineffectiveness in ACS, side effects of canakinumab). The hypothesis follows logically from the cited evidence. Limitations of prior research (e.g., lack of T-cell-targeted therapies in ACS) are explicitly addressed.

Sub-criteria

prior work citedADEQUATE

premise rationaleADEQUATE

limitations addressedADEQUATE

Per reviewer (3) — the votes behind the verdict

PASSReviewer 1· 95% conf

The scientific premise is well-established with comprehensive citation of prior work and a clear rationale linking Treg deficiency in ACS to the hypothesis that low-dose IL-2 reduces inflammation.

Evidence

paraphrase[Main, first paragraph]

“Studies have demonstrated that T reg cell numbers are reduced and their function impaired in ACSs... In pre-clinical studies, increasing T reg cells led to reduced atherosclerosis... We previously demonstrated that low-dose IL-2 was safe and led to a selective statistically significant increase in T reg cells in patients with both ACS and stable ischemic heart disease.”

direct quote[Main, last paragraph of introduction]

“In the trial of low-dose IL-2 for the reduction of vascular inflammation in ACSs (IVORY), we hypothesized that low-dose IL-2 would reduce arterial inflammation compared to placebo in patients presenting with ACSs who have residual inflammation detected by high-sensitivity C-reactive protein (hsCRP) levels >2 mg l −1 .”