Oral ivermectin versus 5% permethrin cream to treat children and adults with classic scabies: multicentre, assessor blinded, cluster randomised clinical trial.
Boralevi F, Simon G, Bernigaud C, Brun J, Goujon E, Perrot JL, Phan A, Hérissé AL, Maruani A, Vanhaecke C, Couty E, Abasq-Thomas C, Fournet M, Mallet S, Brenaut E, Hubiche T, Balguerie X, Caux F, Beneton N, Dutkiewicz AS, Adamski H, Aubert H, Bourrat E, Couzan C, Eyraud A, Janela-Lapert R, Marti A, Miquel J, Richard M, Barbarot S, Bonniaud B, Chabbert C, Delion F, Dinulescu M, Duong TA, Etienne M, Hirsch G, Isnard C, Huet F, Le Bidre E, Leducq S, Legrand A, Monestier S, Morice-Picard F, Seneschal J, Capelli A, Lacoste C, Labrèze C, Miraglia G, Do-Pham G, Giraudeau B, Chosidow O
- DOI
- 10.1136/bmj-2025-086277
- 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/8afd4d42-08a0-4b78-b86d-4bac4bbc626d is authoritative.
How this rating was calculated
Started at 5★ — no deductions. Nothing the checks ran surfaced a material problem.
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 cluster-randomised trial comparing ivermectin and permethrin for scabies. The paper demonstrates strong methodological rigor in randomization, blinding, and statistical analysis, with clear reporting of ethics, resources, and limitations. Minor gaps include the lack of a detailed data access procedure for patient-level data and the sample size calculation not accounting for clustering.
Both reviewers classified the study as interventional, and this was adopted. The evaluation covered all eight dimensions; several sub-criteria were marked not applicable due to the human clinical trial context (e.g., species/strain, housing, cell line authentication). The reviewers diverged slightly on the data availability statement and the adequacy of the power analysis, but these did not affect the overall pass status.
Numerical inconsistencies
None foundValues 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.
Checked — nothing surfaced.
Recomputed 3 tests: 3 consistent, 0 inconsistent; 3 via agent-written checks.
- CONSISTENTreported p < .001 · recomputed p = <.001Reviewer 1Primary cluster-level cure rate difference (ivermectin vs permethrin) from multiple imputation analysis.
“–16.7 percentage point difference, 95% confidence interval (CI) –26.3 to –7.1”
Taken as given: The 95% CI is two-sided and symmetric on the risk difference scale.; The estimate and CI are from the mixed model with multiple imputation.Method: Two-tailed p-value derived from the estimate and 95% CI using the normal approximation (pCI function).How we recomputed it: pCI(-16.7, -26.3, -7.1, 0) - CONSISTENTreported p < .001 · recomputed p = <.001Reviewer 1Secondary outcome: index case cure rate difference.
“–14.9 percentage point difference, 95% CI –23.6 to –6.2”
Taken as given: The 95% CI is two-sided and symmetric.; The estimate and CI are from the mixed model.Method: Two-tailed p-value from estimate and 95% CI using normal approximation.How we recomputed it: pCI(-14.9, -23.6, -6.2, 0) - CONSISTENTreported p < .002 · recomputed p = .002Reviewer 1Secondary outcome: all participants cure rate difference.
“–9.2 percentage point difference, –14.9 to –3.5”
Taken as given: The 95% CI is two-sided and symmetric.; The estimate and CI are from the mixed model with two random effects.Method: Two-tailed p-value from estimate and 95% CI using normal approximation.How we recomputed it: pCI(-9.2, -14.9, -3.5, 0)
Overstated conclusions
1 finding · worst lowConclusions 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
7 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 1The trial's early termination did not affect the results.The authors argue that the sample size was still substantial and the results were clear, but the early termination is a potential source of bias that is not fully addressed.Evidence: Discussion: 'the sample size was substantial, with a theoretical lack of power not affecting the final results.'
“the sample size was substantial, with a theoretical lack of power not affecting the final results.”
DiscussionFind in source - supportedReviewers 1, 2Oral ivermectin is not non-inferior to 5% permethrin cream for clinical cure of scabies on day 28.The primary analysis shows the lower bound of the 95% CI for the cure rate difference is below the -10% non-inferiority margin, supporting the claim.Evidence: Table 3: cluster-level cure rate difference -16.7% (95% CI -26.3 to -7.1).
“Cluster level cure rates were 71.8% versus 88.5% (–16.7 percentage point difference, 95% confidence interval (CI) –26.3 to –7.1) for ivermectin versus permethrin.”
AbstractFind in source - supportedReviewer 15% permethrin cream is statistically superior to oral ivermectin for curing scabies.The upper bound of the 95% CI for the cure rate difference is below 0, indicating statistical superiority of permethrin.Evidence: Table 3 and Figure 2: all 95% CIs for cure rate differences are below 0.
“the trial showed the statistical superiority of 5% permethrin cream.”
ConclusionFind in source - supportedReviewer 1The results are generalizable to patients without diffuse eczematisation or extensive impetiginisation.The inclusion criteria explicitly excluded such patients, so the claim is accurate and appropriately limited.Evidence: Methods: exclusion criteria and Discussion limitations.
“The generalisability of our results is restricted to patients without diffuse eczematisation or extensive impetiginisation.”
LimitationsFind in source - supportedReviewer 25% permethrin cream is statistically superior to oral ivermectin for clinical cure of scabies.The upper bound of the 95% CI for the difference is below zero, indicating statistical superiority of permethrin.Evidence: The 95% CI upper limit was <0, supporting superiority of permethrin.
Furthermore, because the 95% CI upper limit was <0, the result supports the statistical superiority of permethrin.
Results ¶1reviewer’s wording - supportedReviewer 2The trial's results are generalisable to patients without diffuse eczematisation or extensive impetiginisation.The exclusion criteria are clearly stated, and the limitation is acknowledged in the discussion.Evidence: Exclusion criteria and limitation statement.
“Index cases and cluster members were not included if one individual had received a scabicide in the preceding four weeks, or had diffuse eczematisation or extensive impetiginisation.”
LimitationsFind in source - supportedReviewer 2The trial was registered prospectively.The trial registration number is provided, and the ethics statement indicates approval in October 2014, before the trial start in January 2016.Evidence: Trial registration number and ethics approval date.
“The trial was registered prospectively with ClinicalTrials.gov ( NCT02407782 ) and EudraCT (2014-002493-36).”
AbstractFind in source
Efficacy claim is anchored to an adequate endpoint and a meaningful effect.
- ADEQUATESurrogate endpointThe primary endpoint is clinical cure of scabies, defined as disappearance of clinical signs and symptoms (pruritus, burrows, papules/vesicles) assessed by a masked dermatologist. This is a clinical outcome, not a surrogate biomarker.
“The primary outcome was clinical cure of the cluster on day 28 (ie, disappearance of clinical signs and symptoms of scabies for all cluster members).”
- ADEQUATEEffect sizeThe effect size is reported as a difference in cure rates between treatments, with confidence intervals. The trial showed permethrin was superior to ivermectin, with a difference of -16.7 percentage points (95% CI -26.3 to -7.1) at cluster level. This is a clinically meaningful difference in a hard clinical outcome.
“Cluster level cure rates were 71.8% versus 88.5% (–16.7 percentage point difference, 95% confidence interval (CI) –26.3 to –7.1) for ivermectin versus permethrin.”
Data authenticity concerns
None foundAn 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
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 cites prior research on scabies prevalence, treatment options, and two Cochrane systematic reviews with contradictory conclusions. It identifies five methodological flaws in prior RCTs that the current study aims to address, such as lack of dermoscopic confirmation, cluster design, and assessor blinding. The rationale linking these gaps to the study objectives is clear and logical.
“the conclusions of two Cochrane systematic reviews, published in 2007 and 2018, were contradictory: permethrin superiority or no difference in efficacy between the drugs, possibly explained by endpoint differences.”
“five methodological flaws potentially account for the research gap (ie, the lack of study consensus on the superiority or non-inferiority of a drug).”
“The non-inferiority or superiority of both scabicide drugs is uncertain, and therefore we conducted a cluster designed, assessor blinded, randomised controlled trial comparing oral ivermectin with 5% permethrin cream for children and adults with classic scabies.”
“the conclusions of two Cochrane systematic reviews, published in 2007 and 2018, were contradictory: permethrin superiority or no difference in efficacy between the drugs, possibly explained by endpoint differences.”
“five methodological flaws potentially account for the research gap (ie, the lack of study consensus on the superiority or non-inferiority of a drug).”
“The non-inferiority or superiority of both scabicide drugs is uncertain, and therefore we conducted a cluster designed, assessor blinded, randomised controlled trial comparing oral ivermectin with 5% permethrin cream for children and adults with classic scabies.”
Randomization was performed with a 1:1 ratio using blocks of four, stratified by centre, with an independent statistician generating the list. The unit of randomization was the household (cluster). Assessor blinding was implemented, and the open-label design for participants is justified by feasibility. A sample size calculation was provided, though the target was not met due to early termination. Inclusion/exclusion criteria are clearly defined. Missing data were handled with multiple imputation. Outlier handling is not explicitly discussed but is addressed through the pre-specified analysis populations (completer, compliant).
“An independent statistician, not involved in the recruitment of index cases or clusters, generated a 1:1 randomisation list with blocks of four, grouped according to centre.”
“Only endpoint assessors were masked.”
“Assuming a 2.5% one sided type I error rate and 80% power, recruitment of 502 clusters was required.”
“An independent statistician, not involved in the recruitment of index cases or clusters, generated a 1:1 randomisation list with blocks of four, grouped according to centre.”
“Only endpoint assessors were masked.”
“Assuming a 2.5% one sided type I error rate and 80% power, recruitment of 502 clusters was required.”
Sex, age, weight, and health status (e.g., atopic dermatitis, corticosteroid use) are reported in detail for index cases and cluster members in Tables 1 and 2. Demographics are adequately covered. Since this is a human study, species/strain and housing conditions are not applicable.
“Median (IQR) age (years) | 15.9 (7.9-29.9) | 15.8 (8.0-27.5)”
The trial was approved by the French National Ethics Committee (CPP SOOM 3) and the National Agency for the Safety of Medicines and Health Products (ANSM). Written informed consent was obtained from all participants. Compliance with the Declaration of Helsinki and CONSORT guidelines is stated.
“The trial protocol was designed by the national principal investigator and approved by the local principal investigators, the French National Ethics Committee (CPP SOOM 3), and the National Agency for the Safety of Medicines and Health Products (ANSM).”
“All participants (ie, adults, children’s parents or legally authorised representatives, and children) provided written informed consent.”
“Our report followed the Consolidated Standards of Reporting Trials (CONSORT) guideline for parallel group randomised trials and its extension to non-inferiority and cluster trials.”
“The trial protocol was designed by the national principal investigator and approved by the local principal investigators, the French National Ethics Committee (CPP SOOM 3), and the National Agency for the Safety of Medicines and Health Products (ANSM).”
“All participants (ie, adults, children’s parents or legally authorised representatives, and children) provided written informed consent.”
The study drugs are named with manufacturer (MSD-Merck for ivermectin, Codexial for permethrin) and dosing regimen. Statistical software (SAS version 9.4) is identified. No other key biological resources (antibodies, cell lines) are used, so those criteria are not applicable.
“oral ivermectin and topical 5% permethrin were provided free of charge by MSD-Merck and Codexial, respectively”
“For statistical analyses, we used SAS version 9.4 software.”
“the cluster was randomly assigned, in a 1:1 ratio, to receive oral ivermectin 200 µg/kg taken with food (tablets could be crushed for children) or 5% permethrin cream, on day 0 and day 10.”
“For statistical analyses, we used SAS version 9.4 software.”
The primary analysis uses mixed models with risk difference estimation. Exact p-values are not reported; instead, 95% confidence intervals are provided, which is appropriate for a non-inferiority trial. Effect sizes with CIs are reported for all primary and secondary outcomes. Statistical software is identified. Data presentation includes per-group Ns and confidence intervals. Mathematical plausibility checks are not applicable due to continuous outcomes and large sample sizes.
“For cluster level and index case outcomes, mixed models were fitted with the centre considered random. The identity link function was used, which allowed estimations of risk difference.”
“–16.7 (–26.3 to –7.1)”
“For statistical analyses, we used SAS version 9.4 software.”
“Cluster level cure rates were 71.8% versus 88.5% (–16.7 percentage point difference, 95% confidence interval (CI) –26.3 to –7.1) for ivermectin versus permethrin.”
“For cluster level and index case outcomes, mixed models were fitted with the centre considered random.”
A data availability statement is present: codes are available at a Dryad repository. The trial is registered at ClinicalTrials.gov (NCT02407782). Individual patient data are not deposited, which is standard for clinical trials due to privacy concerns. The paper does not explicitly state a data access procedure for patient-level data, but the code sharing is adequate.
“Codes are available at https://doi.org/10.5061/dryad.sn02v6xjd .”
“Trial registration NCT02407782 .”
“The trial protocol along with the statistical analysis plan are available as supplementary files on bmj.com (http://bmj.com) .”
“Codes are available at https://doi.org/10.5061/dryad.sn02v6xjd .”
Methods are detailed enough for replication. The trial is registered. CONSORT guidelines are referenced. All outcomes are reported, including negative results (ivermectin non-inferiority not shown). Limitations are discussed in a dedicated section. Conclusions are proportional to the evidence. Funding sources and competing interests are disclosed.
“Our report followed the Consolidated Standards of Reporting Trials (CONSORT) guideline for parallel group randomised trials and its extension to non-inferiority and cluster trials.”
“Our study had some limitations. The generalisability of our results is restricted to patients without diffuse eczematisation or extensive impetiginisation.”
“The study was funded by the French Ministry of Health (Programme Hospitalier de Recherche Clinique, PHRC-N 2011) and the French Society of Dermatology.”
“Trial registration NCT02407782 .”
“Our report followed the Consolidated Standards of Reporting Trials (CONSORT) guideline for parallel group randomised trials and its extension to non-inferiority and cluster trials.”
“Our study had some limitations.”
Registered (2 IDs: ClinicalTrials.gov, EudraCT). Reporting guideline cited: CONSORT.
Broken references and links
None foundReferences 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 43 references by DOI: 39 verified — 4 no DOI (shown, not verified).
- NO DOIPoints to consider on switching between superiority and non-inferiorityNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIAbout ScabiesNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIThe use of ELM to monitor the success of antiscabietic treatment. Epiluminescence light microscopyNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIScabiesNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
1 data/code link checked; 1 live.
- dataDryadLIVEHTTP 200https://doi.org/10.5061/dryad.sn02v6xjdResolves to Dryad (data repository).
Copyediting
5 minorWording, consistency and formatting errors that need correcting before submission.
No major wording or formatting errors. 5 minor suggestions below.
5 copyedit issues flagged: mostly typo, clarity, consistency.
- MINORtypoAbstract, Results“507 participants in 142 households (clusters) were treated with ivermectin and 568 participants in 147 households received permethrin.”→ Consider rephrasing for consistency: 'were treated with ivermectin' and 'received permethrin' could be unified.Minor inconsistency in verb choice.
- MINORclarityMethods, Sample size and statistical methods“Because the primary outcome was a cluster level outcome, the associated unit of randomisation, analysis, and inference was the household. Therefore, sample size calculation was standard (ie, without considering any clustering) on the basis of the hypothesis that the cluster level cure rate would be 80% in each arm, with a 10% non-inferiority margin.”→ Clarify that the sample size calculation did not account for clustering, which is unusual for a cluster trial; explain why this was acceptable.Potential methodological concern, but the authors address it in the discussion.
- MINORconsistencyAbstract, Results“507 participants in 142 households (clusters) were treated with ivermectin and 568 participants in 147 households received permethrin.”→ Use consistent terminology: 'treated with' vs 'received' could be unified.Minor wording inconsistency.
- MINORtypoResults, paragraph 4“related to the study drug related”→ Remove duplicate 'related'.Typographical error.
- MINORclarityDiscussion, Interpretation and strengths“The ideal double blind, double dummy design was not undertaken because of poor feasibility.”→ Clarify why double-dummy was not feasible, as this is a potential source of bias.Could be more explicit.
The published work is robust and well-reported. An informed reader should weigh the minor reporting gaps (patient-level data access, sample size calculation ignoring clustering) and the copyedit issues, but none of these undermine the core findings. No erratum or re-analysis is warranted based on the available evidence.
- 1.MEDIUMdata codeAdd a managed-access procedure for individual patient data in the Data Availability section, specifying how researchers can request access (e.g., via a data access committee).The current statement is vague for patient-level data, and a clear access route would strengthen reproducibility and transparency.
- 2.MEDIUMstatisticsClarify in the Methods (Sample size and statistical methods) that the sample size calculation did not account for clustering, and explain why this was acceptable or how it was addressed.The sample size calculation ignoring clustering is a methodological concern that readers may question; explicit justification would preempt criticism.
- 3.MEDIUMreportingReport exact p-values alongside confidence intervals for primary and secondary outcomes, or explicitly state why they are not reported.Exact p-values facilitate meta-analyses and are expected by some readers, even though the estimation approach is acceptable.
- 4.MEDIUMreportingAdd a statement on outlier handling in the statistical methods, even if no outliers were identified.Transparency about outlier handling improves reproducibility and completeness of the statistical methods.
- 5.LOWcopyeditFix the duplicate word 'related' in Results, paragraph 4.Typographical error that should be corrected for clarity.
- 6.LOWcopyeditUnify the verb choice in the Abstract Results: use 'were treated with' consistently for both arms.Minor inconsistency in wording that could be polished.
- 7.LOWcopyeditClarify in the Discussion why the double-blind, double-dummy design was not feasible.The current statement is brief; more detail would address potential bias concerns.
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.