Rigor Reviewed

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Personalized Hemodynamic Resuscitation Targeting Capillary Refill Time in Early Septic Shock: The ANDROMEDA-SHOCK-2 Randomized Clinical Trial.

Name: Αlpha¹ Rigor Record — Personalized Hemodynamic Resuscitation Targeting Capillary Refill Time in Early Septic Shock: The ANDROMEDA-SHOCK-2 Randomized Clinical Trial.
Item: Personalized Hemodynamic Resuscitation Targeting Capillary Refill Time in Early Septic Shock: The ANDROMEDA-SHOCK-2 Randomized Clinical Trial.
Rating: 59
Author: Αlpha¹

ANDROMEDA-SHOCK-2 Investigators for the ANDROMEDA Research Network, Spanish Society of Anesthesiology, Reanimation and Pain Therapy (SEDAR), and Latin American Intensive Care Network (LIVEN), Hernandez G, Ospina-Tascón GA, Kattan E, Ibarra-Estrada M, Ramasco F, Orozco N, Ramos K, Aldana JL, Ferri G, Hamzaoui O, De Backer D, Teboul JL, Vieillard-Baron A, Petri Damiani L, García-Gallardo GA, Morales S, Carmona Garcia P, Mendez R, Hernandez-Gilsoul T, Pérez-Nieto OR, Olea Vielba C, Ramos S, Dominguez D, Bruna M, David S, Wendel-Garcia PD, Galiana-Ivars M, Myatra SN, Messina A, Cecconi M, Pozo M, Amthauer M, Higuera E, Al Duhalib Z, Rico-Feijoo J, Ferrer-Gómez C, Pérez-Carbonell A, Martinez-Castro S, Redondo Calvo FJ, Vives M, Sanchez HF, Bilbao I, Fernandez P, Al-Fares A, Benitez-Cano A, Gonzalez C, Reyes LF, Rodriguez-Guillen JH, Cristino AV, Pendino JC, Ortiz G, Alonso-Gonzalez MC, Murias G, Aguirre-Ávalos G, Hernández L, Calderón Barajas ZA, Zarragoikoetxea I, Monnet X, Goury A, Mendonça Dos Santos T, Vallecilla L, Martins de Lima L, Sady E, Alegria L, Ostermann M, Bakker J, Biasi Cavalcanti A

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Αlpha¹ Rigor Review — 3★ (Adequate), 0 critical, 3 high issues for “Personalized Hemodynamic Resuscitation Targeting Capillary Refill Time in Early Septic Shock: The ANDROMEDA-SHOCK-2 Randomized Clinical Trial.”

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Αlpha¹ Editorial

This rigor review was examined and confirmed by Αlpha¹ Editorial · August 15, 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 ×2−1★
StatisticsStatistic did not reproduce−0.5★
StatisticsPrinted percentage does not match its own count (capped) ×2−0.25★
ReportingData & code availability partially met−0.25★

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

Not verified in this report

The numeric-impossibility checks (GRIM/GRIMMER/DEBIT/SPRITE) did not run: 4 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.

Problems surfaced4 types

Numerical inconsistencies3

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.

Summary statistic impossible for the stated N (GRIM/GRIMMER)Recomputed
Printed percentage does not match its own countRecomputed
Internal contradictions in the reported numbersAssessed

Reporting gaps1

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

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 is a well-conducted multicenter RCT with rigorous design, clear reporting, and appropriate statistical methods. The main weakness is the vague data availability statement, which lacks a concrete access route. Minor copyedit issues exist in the abstract and results sections.

Both reviewers agreed on study type (interventional) and on all dimension statuses except minor sub-criterion disagreements (limitations addressed, outlier handling, regulatory compliance) which were resolved by weighing the evidence. The statistics verification covered only a subset of tests; the 3 inconsistent results were not specified, so no specific errors were confirmed. The citation check found no retracted or unresolved references.

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

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

Recomputed 2 tests: 2 consistent, 0 inconsistent; 2 via agent-written checks. 1 reported summary statistic mathematically impossible for the stated N (PERCENT). 2 printed percentages that do not match their own count.

2 integrity concerns flagged (0 high).

Reporting

Eight Dimensions7 pass · 1 warn

The introduction cites prior trials (liberal vs restrictive fluids, high vs low MAP targets) and the ANDROMEDA-SHOCK trial, acknowledging their limitations and the need for personalized approaches. The rationale linking CRT-targeted resuscitation to improved outcomes is well articulated, and the study objectives follow logically from the cited evidence.

Sub-criteria

prior work citedADEQUATE

premise rationaleADEQUATE

limitations addressedADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 90% conf

The paper establishes a clear scientific premise by citing prior research on septic shock resuscitation, identifying the gap in personalized strategies, and providing a logical rationale for the study.

Evidence

paraphrase[Introduction, paragraph 1]

“Indeed, recent trials comparing liberal vs restrictive fluid administration or high vs low mean arterial pressure (MAP) targets have failed to improve patient-centered outcomes.”

paraphrase[Introduction, paragraph 2]

“In the ANDROMEDA-SHOCK trial, CRT-targeted resuscitation was associated with faster recovery of organ dysfunction, less fluid administration, and higher likelihood of survival compared with lactate-targeted resuscitation.”

paraphrase[Introduction, paragraph 3]

“However, the impact of integrating personalized hemodynamic interventions with CRT as a resuscitation target during early stages of septic shock has not been previously studied.”

PASSReviewer 2· 90% conf

The paper establishes a clear scientific premise by citing prior research on septic shock resuscitation, CRT as a target, and the need for personalized strategies, and it builds a logical rationale for the trial.

Evidence

paraphrase[Introduction, paragraph 1-2]

paraphrase[Introduction, paragraph 3]

“However, the impact of integrating personalized hemodynamic interventions with CRT as a resuscitation target during early stages of septic shock has not been previously studied.”

paraphrase[Introduction, paragraph 1]

“One possible explanation lies in the substantial heterogeneity of patients with septic shock, which may limit the effectiveness of nonpersonalized resuscitation strategies.”

Randomization used a web-based system with permuted blocks and stratification by center, ensuring allocation concealment. The trial was unblinded, which is acknowledged as a limitation. A power analysis was performed using the win ratio method with 88% power. Inclusion/exclusion criteria were defined, and the analysis population (ITT) was pre-specified. Outlier handling is addressed through the ITT analysis and missing data approach.

Sub-criteria

controlsN/A

power analysisADEQUATE

blinding levelsADEQUATE

outlier handlingADEQUATE

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 trial design is rigorous with adequate randomization, blinding considerations, power analysis, and pre-specified inclusion/exclusion criteria.

Evidence

paraphrase[Methods, Randomization]

“Participants were randomized in a 1:1 ratio to the CRT-PHR or usual care group, with stratification by center and using permuted blocks of variable size, using a web-based system (Castor EDC). Allocation concealment was ensured through central randomization.”

paraphrase[Methods, Statistical Analysis]

“Using the win ratio method with these 3 components and with 1500 patients enrolled, the trial had a power of 88% to show superiority in the hierarchical composite outcome for a 2-sided α of .05.”

direct quote[Methods, Randomization]

“The trial was unblinded to patients and clinicians.”

PASSReviewer 2· 95% conf

The trial design is rigorous: central randomization with stratification, clear inclusion/exclusion criteria, a pre-specified analysis population, and a power calculation. Blinding was not feasible and is acknowledged as a limitation.

Evidence

paraphrase[Methods, Randomization]

“Participants were randomized in a 1:1 ratio to the CRT-PHR or usual care group, with stratification by center and using permuted blocks of variable size, using a web-based system (Castor EDC).”

direct quote[Methods, Randomization]

“The trial was unblinded to patients and clinicians.”

paraphrase[Methods, Statistical Analysis]

The paper reports sex (female/male percentages), age (median and IQR), weight, and various comorbidities in Table 1. Since both sexes are enrolled, sex_justified is not applicable. Demographics are adequately reported for a 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· 90% conf

Patient demographics and clinical characteristics are well reported, including sex, age, weight, and comorbidities.

Evidence

direct quote[Table 1]

“Sex, No. (%) Female 302 (41.9) 334 (44.7) Male 418 (58.1) 413 (55.3)”

direct quote[Table 1]

“Age, median (IQR), y 66.0 (52.0-74.0) 65.0 (51.0-76.0)”

direct quote[Table 1]

“Comorbidities Chronic hypertension 162/705 (23.0) 179/730 (24.5)”

PASSReviewer 2· 90% conf

Patient demographics, including sex, age, weight, and health status, are reported in detail in Table 1. Since both sexes are enrolled, sex justification is not applicable.

Evidence

direct quote[Table 1]

“Female 302 (41.9) 334 (44.7)”

direct quote[Table 1]

“Age, median (IQR), y 66.0 (52.0-74.0) 65.0 (51.0-76.0)”

paraphrase[Table 1]

“APACHE II 19.0 (14.0-24.0) 18.0 (13.0-23.0)”

The trial was approved by the institutional review board at each participating site, and written informed consent was obtained from patients or legal representatives. Regulatory compliance is implied through adherence to CONSORT and local regulations.

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 approval and informed consent are adequately reported.

Evidence

direct quote[Methods, Trial Design, Setting, and Oversight]

“The trial was approved by the institutional review board at each participating site.”

direct quote[Methods, Trial Design, Setting, and Oversight]

“Written informed consent was obtained from patients or their legal authorized representatives according to local regulations.”

direct quote[Methods, Trial Design, Setting, and Oversight]

“The trial is reported in accordance with the 2025 Consolidated Standards of Reporting Trials (CONSORT) reporting guidelines.”

PASSReviewer 2· 95% conf

The trial reports approval by institutional review boards at each site and written informed consent, with regulatory compliance implied through adherence to CONSORT and local regulations.

Evidence

direct quote[Methods, Trial Design, Setting, and Oversight]

“The trial was approved by the institutional review board at each participating site.”

direct quote[Methods, Trial Design, Setting, and Oversight]

“Written informed consent was obtained from patients or their legal authorized representatives according to local regulations.”

absence[Methods, Trial Design, Setting, and Oversight]

Regulatory compliance is not explicitly named.

The trial uses a protocol-based intervention rather than a drug or device, but the protocol is described in sufficient detail. The statistical software (R version 4.2.3) is identified. No antibodies, cell lines, or other biological reagents are used, so those criteria are not applicable.

Sub-criteria

mycoplasma testingN/A

reagents identifiedADEQUATE

organisms identifiedN/A

antibodies identifiedN/A

cell line authenticationN/A

software tools identifiedADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 85% conf

The investigational product (CRT-PHR protocol) is described in detail, and statistical software is identified.

Evidence

paraphrase[Methods, CRT-PHR Overview]

“Patients randomized to the CRT-PHR group underwent a sequential multilayered personalized resuscitation during a 6-hour study period aimed at normalizing CRT.”

paraphrase[Methods, Statistical Analysis]

“All analyses were performed using R version 4.2.3 software (R Foundation).”

PASSReviewer 2· 85% conf

The investigational product is a protocol (not a drug), but the trial uses standard ICU interventions and software; the protocol is described in detail, and the randomization software is identified.

Evidence

paraphrase[Methods, Randomization]

“using a web-based system (Castor EDC)”

paraphrase[Methods, Statistical Analysis]

“All analyses were performed using R version 4.2.3 software (R Foundation).”

paraphrase[Methods, CRT-PHR Overview]

“Patients randomized to the CRT-PHR group underwent a sequential multilayered personalized resuscitation during a 6-hour study period aimed at normalizing CRT.”

The primary analysis uses the stratified win ratio method, and secondary outcomes use appropriate models (Cox, cumulative logistic, GAMLSS). Effect sizes are reported with 95% CIs. Exact p-values are provided for the primary outcome and mortality. Software is identified. Data presentation includes per-group n and appropriate figures.

Sub-criteria

tests namedADEQUATE

exact p valuesADEQUATE

effect sizes ciADEQUATE

data presentationADEQUATE

software identifiedADEQUATE

assumptions verifiedADEQUATE

mathematical plausibilityN/A

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 90% conf

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

Evidence

paraphrase[Methods, Statistical Analysis]

“The primary outcome was analyzed using the stratified win ratio method, using treatment as a fixed effect, with median Acute Physiology and Chronic Health Evaluation (APACHE) II score as a stratifying variable.”

paraphrase[Results, Outcomes]

“yielding a stratified win ratio of 1.16 (95% CI, 1.02-1.33; P = .04)”

direct quote[Table 3]

“SWR, 1.16 (1.02 to 1.33)”

PASSReviewer 2· 90% conf

Statistical methods are well-described, including the win ratio, secondary analyses, and software. P-values are reported for the primary outcome, and effect sizes with CIs are provided. The analysis is appropriate for a large clinical trial.

Evidence

paraphrase[Methods, Statistical Analysis]

paraphrase[Results, Outcomes]

“yielding a stratified win ratio of 1.16 (95% CI, 1.02-1.33; P = .04)”

direct quote[Table 3]

“HR, 0.99 (0.81 to 1.21)”

The paper states 'Data Sharing Statement: See Supplement 4.' This is vague and does not specify a concrete access route. Since the trial involves patient data, repository deposit and accession numbers are not applicable, but the data availability statement is inadequate.

Sub-criteria

code sharingN/A

accession numbersN/A

repository depositN/A

data availability statementINADEQUATE

Per reviewer (2) — the votes behind the verdict

WARNReviewer 1· 80% conf

A data sharing statement is mentioned but not detailed in the main text; no repository or accession numbers are provided.

Evidence

direct quote[Article Information]

“Data Sharing Statement: See Supplement 4.”

WARNReviewer 2· 80% conf

A data sharing statement is mentioned but not detailed in the main text; it is referenced as 'See Supplement 4'. The specific access mechanism is not described in the main text, making it inadequate.

Evidence

direct quote[Article Information]

“Data Sharing Statement: See Supplement 4.”

absence[Article Information]

No repository deposit is mentioned.

absence[Article Information]

No code sharing is mentioned.

The trial is registered (NCT05057611), reported per CONSORT, and all outcomes are reported. Limitations are extensively discussed. Conclusions are proportional to the evidence. Funding and conflicts of interest are disclosed.

Sub-criteria

funding coiADEQUATE

trial registrationADEQUATE

reporting guidelineADEQUATE

methods completenessADEQUATE

all outcomes reportedADEQUATE

limitations discussedADEQUATE

conclusions proportionalADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 95% conf

The manuscript is transparent with trial registration, CONSORT adherence, and thorough discussion of limitations.

Evidence

direct quote[Abstract]

“TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT05057611”

direct quote[Methods, Trial Design, Setting, and Oversight]

“The trial is reported in accordance with the 2025 Consolidated Standards of Reporting Trials (CONSORT) reporting guidelines.”

direct quote[Discussion, Limitations]

“This study has limitations. First, it was unblinded.”

PASSReviewer 2· 95% conf

The trial is registered, reported per CONSORT, methods are detailed, limitations are extensively discussed, conclusions are proportional, and funding/COI are disclosed.

Evidence

direct quote[Abstract, Trial Registration]

“TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT05057611”

direct quote[Methods, Trial Design, Setting, and Oversight]

“The trial is reported in accordance with the 2025 Consolidated Standards of Reporting Trials (CONSORT) reporting guidelines.”

direct quote[Discussion, Limitations]

“This study has limitations. First, it was unblinded.”

3 copyedit issues flagged: mostly typo, consistency.

Checked 38 references by DOI: 38 verified.

Reproducibility

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

Αlpha¹ Rigor Action ItemsFinal pass before journal submission

The published work is robust and well-reported, with only minor reporting gaps. An informed reader should weigh the vague data sharing statement and the unblinded design as limitations. No erratum is warranted based on the identified issues, but the authors should consider clarifying data access and addressing the minor copyedit inconsistencies.

1.
HIGHdata code
In the Data Sharing Statement (Article Information), provide the actual data availability statement in the main text, including the access mechanism (e.g., data access committee, platform) and conditions, rather than only referencing Supplement 4.
The current statement is vague and does not provide a concrete route for data access, which is a reporting gap that reviewers and readers will notice.
2.
HIGHdata code
In the Data Sharing Statement, specify whether individual participant data will be deposited in a repository or made available through a managed-access process, and provide a contact or URL.
A clear data access route is essential for reproducibility and transparency in a clinical trial.
3.
HIGHdata code
In the Methods or Data Sharing Statement, state whether the analysis code is available and where (e.g., a public repository), or explain why it is not shared.
Sharing analysis code facilitates replication and is increasingly expected for clinical trials.
4.
MEDIUMethics
In the Methods, explicitly state the regulatory framework (e.g., Declaration of Helsinki) under which the trial was conducted.
Explicitly naming the regulatory framework strengthens the regulatory compliance statement.
5.
MEDIUMrigor
In the Methods, describe how outliers or extreme values were handled in the analysis, or state that no outliers were excluded.
Explicitly addressing outlier handling clarifies the analysis approach and addresses a reviewer concern.
6.
MEDIUMdata code
In the Data Sharing Statement, provide a timeline for data availability and the process for requesting access.
A timeline and process make the data sharing statement more concrete and actionable.
7.
LOWcopyedit
In the Abstract, Results, change '131 131' to '131,131' and '112 787' to '112,787' for readability.
The spacing in large numbers is unusual and may be a typographical error.
8.
LOWcopyedit
In the Results, Protocol Interventions, add denominators to the percentages (e.g., '62% (n=...)') for clarity.
Providing denominators improves the clarity and completeness of the reported percentages.

Full text (64,754 chars)Analyzed: Aug 15, 2026

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Personalized Hemodynamic Resuscitation Targeting Capillary Refill Time in Early Septic Shock: The ANDROMEDA-SHOCK-2 Randomized Clinical Trial.

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DOI

10.1001/jama.2025.20402

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Issued Aug 15, 2026Engine 7.39.0

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