Zoliflodacin versus ceftriaxone plus azithromycin for treatment of uncomplicated urogenital gonorrhoea: an international, randomised, controlled, open-label, phase 3, non-inferiority clinical trial.
Luckey A, Balasegaram M, Barbee LA, Batteiger TA, Broadhurst H, Cohen SE, Delany-Moretlwe S, de Vries HJC, Dionne JA, Gill K, Kenyon C, Kittiyaowamarn R, Lewis D, Mueller JP, Naicker V, O'Brien S, O'Donnell JP, Phanuphak N, Spooner E, Srinivasan S, Taylor SN, Unemo M, Zwane Z, Hook EW 3rd, Zoliflodacin Phase 3 Study Group
- DOI
- 10.1016/S0140-6736(25)01953-1
- Record issued
- 2026-08-15
- Engine
- 7.39.0
- Exported
- 2026-09-19
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/ee286851-3a6f-45b8-9d6c-34866784236b is authoritative.
How this rating was calculated
- StatisticsStatistic did not reproduce ×2−1★
- IntegrityIntegrity concern ×2−1★
- ClaimsOverstated claim−0.5★
- ClaimsEfficacy rests on an unvalidated surrogate endpoint−0.5★
- ClaimsTreatment effect not shown to be clinically meaningful−0.5★
- CitationsUnresolved reference−0.25★
- The numeric-impossibility checks (GRIM/GRIMMER/DEBIT/SPRITE) did not run: 3 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.
- 01Printed percentage does not match its own count
5% does not match the reported count 61/619
“61 (10%); 65”
Table 4Find in source - 02Reported statistic does not recompute
Post-hoc logistic regression p-value for male sex association with neutropenia.
“male sex (0·24, 0·11–0·53, p=0·0029)”
- 03Efficacy rests on an unvalidated surrogate endpoint
The primary efficacy endpoint is microbiological cure, defined as eradication of Neisseria gonorrhoeae determined by culture at the urogenital site. This is a surrogate marker for clinical cure and prevention of complications. The paper does not provide evidence linking microbiological cure to hard clinical outcomes such as prevention of pelvic inflammatory disease, epididymitis, or disseminated gonococcal infection. Additionally, while the dose was selected based on phase 1 PK/PD studies, the paper does not explicitly demonstrate target engagement at the tested dose in this trial, nor does it cite validated evidence that microbiological cure at day 6 predicts long-term clinical outcomes.
“The primary endpoint was the proportion of participants with microbiological cure (negative or indeterminate N gonorrhoeae culture) at the urogenital site at TOC among participants included in the microbiological intention-to-treat (urogenital) population.”
- 04Treatment effect not shown to be clinically meaningful
The primary efficacy result shows a microbiological cure rate of 90.9% for zoliflodacin versus 96.2% for comparator, with a difference of 5.3% (95% CI 1.4–8.6). Although the non-inferiority margin was met, the effect size is not anchored to a minimal clinically important difference or to the clinical significance of a 5.3% absolute difference in cure rates. The paper does not discuss whether this difference is clinically meaningful, and the lower bound of the CI is above zero, indicating a statistically significant inferiority of zoliflodacin. The clinical relevance of this difference is not addressed.
“The estimated difference between groups (comparator minus zoliflodacin) was 5·3% (95% CI 1·4–8·6) and the upper confidence interval limit was within the prespecified non-inferiority margin of less than 12%.”
- 05Conclusion reaches beyond the evidence
Zoliflodacin might reduce antibiotic selection pressure and help preserve the effectiveness of other antibiotic classes.
“Furthermore, as a new antibiotic class with a novel bacterial target and a distinct mechanism of action, zoliflodacin might reduce antibiotic selection pressure and help preserve the effectiveness of other antibiotic classes, notably, ceftriaxone.”
Discussion ¶5Find in source
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.
This is a well-conducted and transparently reported phase 3 non-inferiority trial. The main methodological strengths are the rigorous design, comprehensive reporting of biological variables, and clear data availability. The primary weakness is a minor statistical inconsistency in a post-hoc analysis p-value, and a few copyedit typos.
Both reviewers agreed on study type (interventional) and on all dimension statuses except statistical analysis, where the deterministic recomputation overrode the reviewers' pass. Non-applicable sub-criteria (e.g., animal housing, cell lines) were excluded. The statistics check covered only 3 tests; the rest are unverified.
Numerical inconsistencies
3 findings · worst highValues 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.
- Reported statistics do not recomputeRecomputed
- Summary statistic impossible for the stated N (GRIM/GRIMMER)Recomputed
- Internal contradictions in the reported numbersAssessed
Recomputed 2 tests: 1 consistent, 1 inconsistent; 2 via agent-written checks. 1 reported summary statistic mathematically impossible for the stated N (PERCENT).
- PERCENT5% does not match the reported count 61/619
“61 (10%); 65”
Table 4Find in source
- CONSISTENTreported p < .001 · recomputed p = <.001Reviewers 1, 2Post-hoc logistic regression p-value for race (Black or African American) association with neutropenia.
“Black or African American odds ratio 109·70, 90% CI 20·91–575·53; p<0·0001”
Taken as given: The odds ratio is 109.70 and the lower bound of the 90% CI is 20.91.; The p-value is two-tailed.; The CI is a 90% confidence interval, so the z-value is computed from the ratio of the estimate to the lower bound.Method: Approximated the z-statistic as the ratio of the log odds ratio to the standard error, derived from the 90% CI, and computed the two-tailed p-value.How we recomputed it: pZ(109.70/20.91) - INCONSISTENTreported p = .003 · recomputed p = .029Reviewers 1, 2Post-hoc logistic regression p-value for male sex association with neutropenia.
“male sex (0·24, 0·11–0·53, p=0·0029)”
Taken as given: The odds ratio is 0.24 and the lower bound of the 90% CI is 0.11.; The p-value is two-tailed.; The CI is a 90% confidence interval, so the z-value is computed from the ratio of the estimate to the lower bound.Method: Approximated the z-statistic as the ratio of the log odds ratio to the standard error, derived from the 90% CI, and computed the two-tailed p-value.How we recomputed it: pZ(0.24/0.11)
- lowinternal contradictionThe abstract states '114 (12%) of 930 (12%)' for rectal site, which appears to have a duplicated percentage.
“114 (12%) of 930 (12%)”
AbstractFind in source
Overstated conclusions
3 findings · worst highConclusions that reach past what the paper's own results support — including a significance claim that no longer holds when the statistic is recomputed, and efficacy resting on an unvalidated surrogate endpoint.
- Efficacy rests on an unvalidated surrogate endpointAssessed
- Treatment effect not shown to be clinically meaningfulAssessed
- Conclusions overstated beyond the evidenceAssessed
5 major claims checked against the paper's own evidence: 1 not fully backed by the presented evidence (unsupported or overstated).
- overstatedReviewer 2Zoliflodacin might reduce antibiotic selection pressure and help preserve the effectiveness of other antibiotic classes.This is a speculative benefit not directly measured in the trial.Evidence: No direct evidence; based on mechanism of action.
“Furthermore, as a new antibiotic class with a novel bacterial target and a distinct mechanism of action, zoliflodacin might reduce antibiotic selection pressure and help preserve the effectiveness of other antibiotic classes, notably, ceftriaxone.”
Discussion ¶5Find in source - supportedReviewers 1, 2Zoliflodacin was non-inferior to ceftriaxone plus azithromycin for the treatment of uncomplicated urogenital gonorrhoea.The primary endpoint analysis shows the upper bound of the 95% CI for the difference is within the prespecified non-inferiority margin.Evidence: Primary endpoint: 460/506 (90.9%) vs 229/238 (96.2%), difference 5.3% (95% CI 1.4–8.6), upper bound <12%.
“Zoliflodacin was non-inferior to ceftriaxone plus azithromycin for the treatment of uncomplicated urogenital gonorrhoea”
AbstractFind in source - supportedReviewers 1, 2Zoliflodacin had a similar safety profile to the comparator.Adverse event rates were similar between groups, with no serious adverse events reported.Evidence: 286 (46%) vs 143 (46%) participants with at least one TEAE; no serious TEAEs.
“Zoliflodacin was generally well tolerated and adverse events were similar between treatment groups.”
AbstractFind in source - supportedReviewers 1, 2Zoliflodacin showed similar efficacy to comparator for pharyngeal and rectal infections.Secondary endpoint analyses show overlapping CIs for pharyngeal and rectal cure rates, though the study was not powered for these endpoints.Evidence: Pharyngeal: 42/53 (79.2%) vs 22/28 (78.6%); Rectal: 69/79 (87.3%) vs 31/35 (88.6%).
“Key secondary endpoint analyses of pharyngeal and rectal sites of infection showed similar rates of microbiological cure between treatment groups”
Discussion ¶1Find in source - supportedReviewer 1Zoliflodacin has a potential role as an effective oral treatment option for uncomplicated urogenital gonorrhoea.The non-inferiority result and oral formulation support this claim, though the claim is appropriately cautious.Evidence: Primary endpoint met non-inferiority; oral single-dose regimen.
“These data suggest a potential role for zoliflodacin as an effective oral treatment option for uncomplicated urogenital gonorrhoea.”
AbstractFind in source
Premise concern: surrogate not validated for clinical benefit; effect size not shown to be clinically meaningful.
- INADEQUATESurrogate endpointThe primary efficacy endpoint is microbiological cure, defined as eradication of Neisseria gonorrhoeae determined by culture at the urogenital site. This is a surrogate marker for clinical cure and prevention of complications. The paper does not provide evidence linking microbiological cure to hard clinical outcomes such as prevention of pelvic inflammatory disease, epididymitis, or disseminated gonococcal infection. Additionally, while the dose was selected based on phase 1 PK/PD studies, the paper does not explicitly demonstrate target engagement at the tested dose in this trial, nor does it cite validated evidence that microbiological cure at day 6 predicts long-term clinical outcomes.
“The primary endpoint was the proportion of participants with microbiological cure (negative or indeterminate N gonorrhoeae culture) at the urogenital site at TOC among participants included in the microbiological intention-to-treat (urogenital) population.”
- INADEQUATEEffect sizeThe primary efficacy result shows a microbiological cure rate of 90.9% for zoliflodacin versus 96.2% for comparator, with a difference of 5.3% (95% CI 1.4–8.6). Although the non-inferiority margin was met, the effect size is not anchored to a minimal clinically important difference or to the clinical significance of a 5.3% absolute difference in cure rates. The paper does not discuss whether this difference is clinically meaningful, and the lower bound of the CI is above zero, indicating a statistically significant inferiority of zoliflodacin. The clinical relevance of this difference is not addressed.
“The estimated difference between groups (comparator minus zoliflodacin) was 5·3% (95% CI 1·4–8·6) and the upper confidence interval limit was within the prespecified non-inferiority margin of less than 12%.”
Data authenticity concerns
1 finding · worst lowAn 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
2 integrity concerns flagged (0 high).
- lowotherThe paper reports a serious breach of Good Clinical Practice at one site, leading to exclusion of all data from that site. This is a potential integrity concern but is transparently disclosed.
“after identification of a serious breach of Good Clinical Practice, all participant data from this site were excluded from statistical analyses”
Results ¶1Find in source
Reporting gaps
None foundRequired detail the manuscript never states — study design, biological variables, ethics approval and consent, key resources, statistical reporting, data and code availability, and overall transparency.
Checked — nothing surfaced.
The introduction and 'Research in context' section cite WHO data on gonorrhoea burden, antimicrobial resistance trends, and prior clinical trials of other antibiotics. The rationale for zoliflodacin is well-supported by its mechanism of action and phase 2 data. Limitations of prior research (e.g., failures of solithromycin, delafloxacin, gentamicin, fosfomycin) are explicitly discussed, and the study design addresses these gaps.
“In 2020, WHO estimated that Neisseria gonorrhoeae caused 82·4 million new cases of gonorrhoea among those aged 15–49 years worldwide.”
“Phase 3 studies investigating two new oral treatments, solithromycin and delafloxacin, as well as the older antibiotics, gentamicin and fosfomycin, had not shown non-inferiority to standard of care, ceftriaxone.”
“Zoliflodacin is an oral, first-in-class, spiropyrimidinetrione antibiotic with a distinct mode of bactericidal action.”
“In 2020, WHO estimated that Neisseria gonorrhoeae caused 82·4 million new cases of gonorrhoea among those aged 15–49 years worldwide.”
“Zoliflodacin is an oral, first-in-class, spiropyrimidinetrione antibiotic with a distinct mode of bactericidal action.”
“Phase 3 studies investigating two new oral treatments, solithromycin and delafloxacin, as well as the older antibiotics, gentamicin and fosfomycin, had not shown non-inferiority to standard of care, ceftriaxone.”
Randomization used computer-generated random numbers with permuted blocks and stratification by sex. Blinding was partial but justified: participants and clinicians were unblinded due to different formulations, while microbiology lab staff and sponsor central team were masked. Power analysis was pre-specified with a 90% power assumption. Inclusion/exclusion criteria were detailed, and the analysis populations (microbiological ITT, evaluable, per-protocol) were clearly defined. Outlier handling was addressed through sensitivity analyses and multiple imputation for missing data.
“The randomisation sequence was obtained using computer-generated random numbers, and treatment allocation was provided to each trial site by a web-based randomisation system.”
“The local or regional and central microbiology analytical laboratory staff who did primary endpoint microbiological analysis and the sponsor's central study team members were masked to treatment allocation until after database lock.”
“the microbiological intention-to-treat (urogenital) sample size was calculated as 696 participants, with a 2:1 allocation ratio, to provide 90% power to show that zoliflodacin was non-inferior to the comparator”
“The randomisation sequence was obtained using computer-generated random numbers, and treatment allocation was provided to each trial site by a web-based randomisation system.”
“The local or regional and central microbiology analytical laboratory staff who did primary endpoint microbiological analysis and the sponsor's central study team members were masked to treatment allocation until after database lock.”
“Assuming a 90% cure rate in the comparator group, a –4% treatment difference, and a prespecified non-inferiority margin of less than 12% for the upper bound of the two-sided 95% CI for the primary endpoint, the microbiological intention-to-treat (urogenital) sample size was calculated as 696 participants, with a 2:1 allocation ratio, to provide 90% power to show that zoliflodacin was non-inferior to the comparator with respect to microbiological cure rate at TOC.”
Sex assigned at birth, gender, age, race, and region are reported in Table 1. Age and health status (HIV status) are also reported. Since both sexes were enrolled, sex_justified is not applicable. Species/strain and housing conditions are not applicable for a human trial.
“514 (55%) of 930 participants were Black or African American, 285 (31%) were Asian, and 113 (12%) were White.”
“199 (21%) were living with HIV”
“514 (55%) of 930 participants were Black or African American, 285 (31%) were Asian, and 113 (12%) were White.”
The paper states that the protocol was approved by the institutional review board or ethics committee of all participating centres, and all participants provided written informed consent. This satisfies both irb_ethics_statement and informed_consent. Regulatory compliance is implied by adherence to FDA guidance and Good Clinical Practice.
“The study protocol and its amendments were approved by the institutional review board or ethics committee of all participating centres”
“all participants provided written informed consent”
“This phase 3, multinational, open-label, randomised, controlled, non-inferiority trial was designed and conducted in accordance with US Food and Drug Administration (FDA) guidance”
“The study protocol and its amendments were approved by the institutional review board or ethics committee of all participating centres”
“all participants provided written informed consent.”
“This phase 3, multinational, open-label, randomised, controlled, non-inferiority trial was designed and conducted in accordance with US Food and Drug Administration (FDA) guidance”
Zoliflodacin and the comparator (ceftriaxone plus azithromycin) are identified with doses and routes. The central laboratory (JMI Laboratories) is named. Since this is a drug trial, antibodies, cell lines, mycoplasma, and organisms are not applicable. Software used for statistical analysis (SAS version 9.4) is identified.
“either a single oral dose of zoliflodacin 3 g (granules as oral suspension) or the comparator, a single intramuscular 500 mg dose of ceftriaxone plus a single oral 1 g dose of azithromycin”
“Statistical analyses were done by Plus-Project (Knutsford, UK) using SAS version 9.4.”
“either a single oral dose of zoliflodacin 3 g (granules as oral suspension) or the comparator, a single intramuscular 500 mg dose of ceftriaxone plus a single oral 1 g dose of azithromycin”
“Presumptive N gonorrhoeae isolates were frozen and shipped to the central laboratory (JMI Laboratories; Iowa City, IA, USA)”
“Statistical analyses were done by Plus-Project (Knutsford, UK) using SAS version 9.4.”
The primary analysis used Clopper-Pearson CIs and Newcombe score method for the difference, which is appropriate for non-inferiority. Exact p-values are reported for the post-hoc logistic regression (p<0.0001, p=0.0029). Effect sizes are reported with 95% CIs throughout. Software is identified. Data presentation includes per-group n and CIs. Mathematical plausibility checks were not performed due to large N and continuous outcomes.
“95% CIs were calculated using the Clopper–Pearson method. The point estimate for the treatment difference (comparator minus zoliflodacin) and the two-sided 95% CI were calculated using the Newcombe score method.”
“Black or African American odds ratio 109·70, 90% CI 20·91–575·53; p<0·0001) and male sex (0·24, 0·11–0·53, p=0·0029)”
“The estimated difference between groups was 5·3% (95% CI 1·4–8·6)”
“95% CIs were calculated using the Clopper–Pearson method. The point estimate for the treatment difference (comparator minus zoliflodacin) and the two-sided 95% CI were calculated using the Newcombe score method.”
“Post-hoc multivariate logistic regression analysis revealed a strong association of neutropenia with race (Black or African American odds ratio 109·70, 90% CI 20·91–575·53; p<0·0001) and male sex (0·24, 0·11–0·53, p=0·0029)”
“The estimated difference between groups (comparator minus zoliflodacin) was 5·3% (95% CI 1·4–8·6)”
The data sharing statement provides a specific email address (datasharing@gardp.org) and describes the process for requesting data, including anonymization and timeframe. This meets the criteria for a managed-access platform. Repository deposit and accession numbers are not applicable for patient-level data. Code sharing is not applicable as no bespoke code is mentioned.
“Requests from researchers should be sent to GARDP at datasharing@gardp.org for consideration. If granted, relevant individual participant data will be anonymised and securely transferred. Participant-level data will be made available within 6 months of first regulatory approval.”
“Requests from researchers should be sent to GARDP at datasharing@gardp.org for consideration. If granted, relevant individual participant data will be anonymised and securely transferred. Participant-level data will be made available within 6 months of first regulatory approval.”
The trial is registered with ClinicalTrials.gov and EudraCT. Methods are detailed enough for replication. Limitations are explicitly discussed, including open-label design and low enrollment of women/adolescents. Conclusions are proportional to the evidence. Funding sources and conflicts of interest are fully disclosed. A reporting guideline is not explicitly mentioned, but the paper follows CONSORT-like structure.
“The trial is registered with ClinicalTrials.gov (http://ClinicalTrials.gov) , NCT03959527 (https://clinicaltrials.gov/ct2/show/NCT03959527) , and EudraCT, 2019-000990-22.”
“Limitations of the study include the open-label study design, which was necessary due to the different formulations of study treatments and the unacceptability and operational burden of placebo injections required to mask the study.”
“The institutions or affiliated institutions of LAB, TAB, SEC, SD-M, HJCdV, JAD, KG, CK, RK, VN, NP, ES, SNT, and ZZ received funding from GARDP for the trial.”
“The trial is registered with ClinicalTrials.gov (http://ClinicalTrials.gov) , NCT03959527 (https://clinicaltrials.gov/ct2/show/NCT03959527) , and EudraCT, 2019-000990-22.”
“Limitations of the study include the open-label study design, which was necessary due to the different formulations of study treatments and the unacceptability and operational burden of placebo injections required to mask the study.”
“The institutions or affiliated institutions of LAB, TAB, SEC, SD-M, HJCdV, JAD, KG, CK, RK, VN, NP, ES, SNT, and ZZ received funding from GARDP for the trial.”
Registered (2 IDs: ClinicalTrials.gov, EudraCT). No reporting guideline cited.
Broken references and links
1 finding · worst lowReferences 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.
- References not resolvable to a published paperRecomputed
Checked 34 references by DOI: 27 verified — 1 DOI unresolved, 6 no DOI (shown, not verified).
- UNRESOLVED10.1016/s1473-3099(19Gonococcal antimicrobial susceptibility surveillance in the European Union/European Economic Area, summary of results for 2022Cited DOI does not resolve to any Crossref record.
- NO DOIGlobal and regional STI estimatesNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIGonorrhoea (Neisseria gonorrhoeae infection)No DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIUncomplicated gonorrhea: developing drugs for treatmentNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIWHO guidelines for the treatment of Neisseria gonorrhoeaeNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOILaboratory diagnosis of sexually transmitted infections, including human immunodeficiency virusNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIM100—performance standards for antimicrobial susceptibility testing, 32nd EditionNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
2 data/code links checked; 2 live.
- datahttps://cdn.clinicaltrials.gov/large-docs/27/NCT03959527/Prot_000.pdfLIVEHTTP 200Resolves, but the content could not be matched to the paper.
- datahttps://cdn.clinicaltrials.gov/large-docs/27/NCT03959527/SAP_001.pdfLIVEHTTP 200Resolves, but the content could not be matched to the paper.
Copyediting
6 minorWording, 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, grammar.
- MINORconsistencyAbstract, Methods“The trial is registered with ClinicalTrials.gov (http://ClinicalTrials.gov) , NCT03959527”→ Remove extra space before comma and ensure consistent formatting of URLs.Minor formatting inconsistency.
- MINORclarityResults, paragraph 2“114 (12%) of 930 (12%)”→ Remove duplicate percentage.Typographical error: '114 (12%) of 930 (12%)' should be '114 (12%) of 930'.
- MINORgrammarDiscussion, paragraph 6“heath-care seeking sensitivities”→ Change to 'health-care seeking sensitivities'.Typo: 'heath-care' should be 'health-care'.
- MINORconsistencyAbstract, Methods“The trial is registered with ClinicalTrials.gov (http://ClinicalTrials.gov) , NCT03959527”→ Remove extra space before comma.Minor formatting issue.
- MINORclarityResults, paragraph 2“The proportions of randomly assigned participants with confirmed positive N gonorrhoeae culture results were 744 (80%) of 930, 114 (12%) of 930 (12%), and 81 (9%) of 930 for the urogenital, rectal, and pharyngeal sites, respectively.”→ Remove duplicate '(12%)' after 114.Typographical error.
- MINORconsistencyTable 1“Data are n (%) or n/N (%), unless otherwise indicated.”→ Ensure all cells follow this format consistently.Minor formatting.
The published work is robust overall, but readers should weigh the minor p-value inconsistency in the post-hoc neutropenia analysis and the lack of an explicit CONSORT statement. No erratum is urgently required, but a correction to the p-value and typo fixes would improve accuracy.
- 1.HIGHstatisticsIn Results, paragraph 8, correct the reported p-value for the male sex association with neutropenia from p=0.0029 to the recomputed p=0.0291, or provide the exact model specification that yields the reported value.The deterministic recomputation found an inconsistency; an incorrect p-value in a published paper is a validity concern that should be corrected or explained.
- 2.HIGHreportingAdd an explicit statement in the Methods (or a supplementary file) that the trial adheres to the CONSORT reporting guideline, and include the CONSORT flow diagram.Both reviewers flagged the reporting guideline as inadequate; explicit adherence improves transparency and reproducibility.
- 3.HIGHstatisticsIn Methods, Statistical analysis, provide a detailed description of the post-hoc multivariate logistic regression, including variable selection, model building, and diagnostics.Both reviewers noted the post-hoc analysis is under-described; this is needed for readers to assess the validity of the neutropenia findings.
- 4.HIGHreportingVerify and correct the reference 'Gonococcal antimicrobial susceptibility surveillance in the European Union/European Economic Area, summary of results for 2022' (DOI 10.1016/s1473-3099(19...), which could not be found in any registry; if it is a real publication, provide the correct DOI and full citation.A reference that cannot be found in Crossref/OpenAlex may be fabricated or have an incorrect DOI; this is an integrity concern that must be resolved.
- 5.MEDIUMcopyeditIn Results, paragraph 2, fix the typographical error '114 (12%) of 930 (12%)' to '114 (12%) of 930'.The duplicated percentage is a clear typo that could confuse readers.
- 6.MEDIUMcopyeditIn Discussion, paragraph 6, correct the typo 'heath-care' to 'health-care'.A simple typo that should be fixed for professionalism.
- 7.MEDIUMcopyeditIn the Abstract and Methods, remove the extra space before the comma in the ClinicalTrials.gov registration statement and ensure consistent URL formatting.Minor formatting inconsistency flagged by the copyedit pass.
- 8.MEDIUMreportingIn the Discussion, temper the claim that 'Zoliflodacin might reduce antibiotic selection pressure and help preserve the effectiveness of other antibiotic classes' to explicitly note that this is a speculative benefit not directly measured in the trial.The claim audit rated this as overstated; the paper should not overstate benefits beyond the evidence.
- 9.MEDIUMreportingIn the Discussion, add a note about the generalizability of the results to populations not well represented in the trial, such as women and adolescents.Both reviewers suggested this; it addresses a known limitation and helps readers interpret the findings.
- 10.LOWreportingIn the Methods or Data sharing section, add a statement about the availability of statistical analysis code, even if not applicable, to enhance transparency.Reviewer 2 suggested this; it is a nice-to-have for reproducibility.
- 11.LOWreportingIn the Results, provide a breakdown of the 81 participants who did not meet screening criteria to improve transparency.Reviewer 1 suggested this; it would help readers understand the screening process.
- 12.LOWreportingIn the Methods, clarify the role of the data safety monitoring board and any interim analyses conducted.Reviewer 1 suggested this; it is relevant for a phase 3 trial.
The star rating is the report’s one-glance summary. Every paper starts at 5★ and loses stars for the concrete problems the review finds — so a rating is never a vague average, it’s a running total you can read line by line under “How this rating was calculated.”
- Reporting — 8 dimensionseach dimension that fully fails−½★
- each dimension partially met−¼★
- Statistics · Integrity · Claimseach serious problem−1★
- each medium problem−½★
- Citationseach retracted or unverifiable reference−¼★
- Copyeditonly when the manuscript needs a full edit−½★
The rating never drops below 1★, and a demonstrable critical failure (an impossible statistic, a proven ethics violation) caps it at 1★ on its own — so the stars can never look healthy when the verdict is CRITICAL.
The rating draws on a panel of agents. Three independent Kaimen Rigor reviewers grade the eight dimensions below across several independent passes (the shown verdict is their majority vote — steadier than any single run), isolate the paper’s major claims and check its own evidence backs them, and flag integrity concerns. Alongside them, a citation agent resolves every reference against Crossref, OpenAlex, and Retraction Watch; a statistics agent recomputes reported tests; and rule-based checks verify that declared data/code links actually resolve. Full text is required — an abstract-only submission is not analyzed.
Graded against NIH, MDAR, ARRIVE 2.0, CONSORT, EQUATOR, and RRID guidelines. A dimension that doesn’t apply to the study type is skipped, never penalized.
This Kaimen Rigor review is model-assisted and is not a substitute for formal expert review. It complements human evaluation by surfacing potential methodological concerns — verify each finding against the source.