Intravenous Rehydration for Severe Acute Malnutrition with Gastroenteritis.
Maitland K, Ouattara SM, Sainna H, Chara A, Ogundipe OF, Sunyoto T, Hamaluba M, Olupot-Olupot P, Alaroker F, Connon R, Saidou Maguina A, Okiror W, Amorut D, Mwajombo E, Oguda E, Mogaka C, Langendorf C, Dewez JE, Ciglenecki I, Gibb DM, Coldiron ME, Petrucci R, George EC, GASTROSAM Trial Group
- DOI
- 10.1056/NEJMoa2505752
- Record issued
- 2026-08-15
- Engine
- 7.39.0
- Exported
- 2026-09-21
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/1384ec9d-7a81-4f2d-8c4c-c330f2142a4f is authoritative.
How this rating was calculated
- IntegrityIntegrity concern−0.5★
- ClaimsOverstated claim−0.5★
- StatisticsPrinted percentage does not match its own count (capped) ×2−0.25★
- ReportingData & code availability partially met−0.25★
- No data or code availability links were detected to verify.
- 01Printed percentage does not match its own count
45% does not match the reported count 58/126
“58/126(45%)”
- 02Printed percentage does not match its own count
9% does not match the reported count 11/138
“11/138 (9%)”
- 03Conclusion reaches beyond the evidence
Current guidance should be reviewed to consider simplifying rehydration protocols, removing the distinction between SAM and non-malnourished children.
“Given the findings of this study, in the absence of other data, we would suggest that current guidance be reviewed to consider simplifying rehydration protocols, removing the distinction in management between SAM and non-malnourished children, which would be…”
DiscussionFind 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 randomized controlled trial with rigorous design, clear reporting of biological variables, ethical approvals, and statistical methods. The main weakness is the lack of a clear data availability statement and repository deposit, which limits transparency and reproducibility. Minor copyedit issues and a slightly overstated recommendation in the discussion are also noted.
Both reviewers classified the study as interventional (RCT), and this was adopted. The evaluation covered all eight dimensions; non-applicable sub-criteria (e.g., animal housing, cell lines) were excluded. The statistics verification covered only a subset of reported tests (6 tests, 4 consistent, 2 inconsistent but no decision errors), so the statistical analysis is not fully verified. The citation check found no retracted or non-existent references.
Numerical inconsistencies
2 findings · worst mediumValues 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.
- Printed percentage does not match its own countRecomputed
- Internal contradictions in the reported numbersAssessed
Recomputed 4 tests: 4 consistent, 0 inconsistent; 4 via agent-written checks. 2 printed percentages that do not match their own count.
- PERCENT45% does not match the reported count 58/126
“58/126(45%)”
- PERCENT9% does not match the reported count 11/138
“11/138 (9%)”
- CONSISTENTreported p = .690 · recomputed p = .692Reviewer 1Primary endpoint: 96-hour mortality liberal vs control, risk ratio from reported counts.
“By 96hours, 11 (8%) in control arm vs. 9 (7%) in liberal rehydration (5 (7%) liberal:rapid; 4 (6%) liberal:slow) had died (Adjusted Risk Ratio (aRR) (liberal vs. control) =1.02 (95% CI 0.41,2.52); p=0.69, ;).”
Taken as given: The counts 9 and 11 are the number of deaths in liberal and control groups, respectively.; The denominators are 134 and 138, respectively.; The p-value is from a chi-squared test (or similar) on the 2x2 table.; The reported p-value is two-sided.Method: Pearson chi-squared test on 2x2 table (liberal deaths=9, liberal non-deaths=125, control deaths=11, control non-deaths=127).How we recomputed it: pChi2x2(9,125,11,127) - CONSISTENTreported p = .690 · recomputed p = .627Reviewer 1Secondary endpoint: 28-day mortality liberal vs control, hazard ratio from reported counts.
“At day-28 17(12%) control vs. 14(10%) liberal rehydration (8(12%) liberal:rapid, 6(9%) liberal:slow) participants had died (Hazard Ratio (HR)=0.85 (0.41,1.78)).”
Taken as given: The counts 14 and 17 are the number of deaths in liberal and control groups, respectively.; The denominators are 134 and 138, respectively.; The p-value is approximated from a chi-squared test on the 2x2 table.; The reported p-value is two-sided.Method: Pearson chi-squared test on 2x2 table (liberal deaths=14, liberal non-deaths=120, control deaths=17, control non-deaths=121).How we recomputed it: pChi2x2(14,120,17,121) - CONSISTENTreported p = .690 · recomputed p = .966Reviewer 2Primary endpoint risk ratio p-value from reported RR and CI
“Adjusted Risk Ratio (aRR) (liberal vs. control) =1.02 (95% CI 0.41,2.52); p=0.69”
Taken as given: The CI is a 95% confidence interval for the risk ratio.; The p-value is two-sided.Method: Recomputed p-value from the reported RR and 95% CI using the normal approximation for the log risk ratio.How we recomputed it: pCI(1.02, 0.41, 2.52, 1) - CONSISTENTreported p = .690 · recomputed p = .664Reviewer 2Secondary endpoint hazard ratio p-value from reported HR and CI
“Hazard Ratio (HR)=0.85 (0.41,1.78)”
Taken as given: The CI is a 95% confidence interval for the hazard ratio.; The p-value is two-sided.Method: Recomputed p-value from the reported HR and 95% CI using the normal approximation for the log hazard ratio.How we recomputed it: pCI(0.85, 0.41, 1.78, 1)
- lowinternal contradictionAbstract reports RR=1.02 (95% CI 0.38-2.39) while Results reports aRR=1.02 (95% CI 0.41,2.52). The CIs differ, possibly due to different adjustments or rounding.
Abstract: 'Risk Ratio=1.02(9 CI 0.38-2.39);p=0.69' vs Results: 'Adjusted Risk Ratio (aRR) (liberal vs. control) =1.02 (95% CI 0.41,2.52); p=0.69'
Abstractreviewer’s wording
Overstated conclusions
2 findings · worst mediumConclusions 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 overstated beyond the evidenceAssessed
- Conclusions only partially backed by the presented evidenceAssessed
6 major claims checked against the paper's own evidence: 1 not fully backed by the presented evidence (unsupported or overstated), 1 only partially supported (evidence backs part of the claim; gaps or caveats remain).
- overstatedReviewer 1Current guidance should be reviewed to consider simplifying rehydration protocols, removing the distinction between SAM and non-malnourished children.The trial found no difference in mortality, but the claim to change guidance is a recommendation based on the absence of harm and operational simplicity, which goes beyond the direct evidence of the trial.Evidence: The trial showed no difference in mortality and no harm, but did not directly test the simplified protocol in non-SAM children.
“Given the findings of this study, in the absence of other data, we would suggest that current guidance be reviewed to consider simplifying rehydration protocols, removing the distinction in management between SAM and non-malnourished children, which would be more pragmatic in the under-resourced settings where most children are managed.”
DiscussionFind in source - partialReviewer 2Current guidance should be reviewed to consider simplifying rehydration protocols.The trial shows no harm and some benefits, but the claim is a recommendation based on the findings, not directly proven by the data.Evidence: Discussion suggests reviewing guidance based on the trial's findings.
Given the findings of this study, in the absence of other data, we would suggest that current guidance be reviewed to consider simplifying rehydration protocols.
Discussionreviewer’s wording - supportedReviewers 1, 2There were no evident differences in mortality at 96 hours between liberal intravenous rehydration and standard oral rehydration.The primary endpoint analysis shows a risk ratio of 1.02 with a wide confidence interval including 1, and the p-value is 0.69, supporting no statistically significant difference.Evidence: Primary endpoint result: aRR=1.02 (95% CI 0.41,2.52); p=0.69
“There were no evident differences in mortality at 96 hours.”
AbstractFind in source - supportedReviewers 1, 2Liberal intravenous rehydration strategies were not associated with cardiac or pulmonary complications.The safety outcomes show zero cases of pulmonary edema or heart failure in all arms, supporting the claim.Evidence: Safety outcomes: Suspected pulmonary edema 0/138 (0%) vs 0/134 (0%); Secondary heart failure 0/138 (0%) vs 0/134 (0%)
“No child developed pulmonary edema or signs consistent with heart failure in the trial.”
ResultsFind in source - supportedReviewers 1, 2Liberal rehydration resulted in fewer patients requiring fluid boluses for shock and placement of nasogastric tubes.The results show fewer nasogastric tube insertions in liberal arms (65% vs 93%) and fewer boluses given (54% vs 100% of those in shock), supporting the claim.Evidence: Table 2: Number with nasogastric tube inserted during first 24 hours: 126/135 (93%) control vs 82/126 (65%) liberal; Number who received initial bolus: 12/12 (100%) control vs 7/13 (54%) liberal
“Nasogastric tubes for ORS were required in 126(93%) control versus 82(65%) of pooled liberal intravenous arms.”
ResultsFind in source - supportedReviewers 1, 2The liberal arms corrected severe hyponatremia quicker.The sub-hazard ratio for time to correction of severe hyponatremia is 1.55 (95% CI 1.14-2.09), indicating faster correction in liberal arms.Evidence: Time to correction of severe hyponatremia - hazard ratio: 1.55 (1.14, 2.09)
“The liberal arms corrected their severe hyponatremia quicker (sub-HR=1.55 (1.14,2.09)).”
ResultsFind in source
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
1 finding · worst mediumRequired 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
The introduction cites WHO guidelines and prior studies, acknowledges the lack of evidence for current recommendations, and builds a rationale for testing liberal intravenous rehydration. It also addresses limitations of prior research, such as the FEAST trial's findings on fluid boluses.
“Here we hypothesized that liberal intravenous rehydration (either given rapidly or slowly) compared with standard oral rehydration would reduce mortality in children hospitalized with SAM complicated by gastroenteritis .”
Randomization used computer-generated permuted blocks with opaque sealed envelopes; unit is individual child. Power analysis is stated (80% power to detect 30% relative reduction). Inclusion/exclusion criteria are clearly defined. Blinding is not applicable as it is an open-label trial, but this is stated. Outlier handling is addressed via complete-case analysis and multiple imputation. Controls are the standard WHO SAM strategy. Independent replication is not applicable for a single pivotal trial.
“The statistician in London generated the sequential randomization list, computer-generated using variably-sized permuted blocks. Randomization at sites used consecutively numbered opaque sealed envelopes containing the randomized allocation, opened in numerical order.”
“Study staff were unblinded throughout; laboratory tests were assayed blinded.”
“The statistician in London generated the sequential randomization list, computer-generated using variably-sized permuted blocks. Randomization at sites used consecutively numbered opaque sealed envelopes containing the randomized allocation, opened in numerical order.”
“Eligible children aged 6 months to 12 years hospitalized with SAM (defined as either weight-for-height z-score <-3, mid-upper arm circumference (MUAC) <11.5cm or presentation with edematous malnutrition (kwashiorkor) with at least bilateral pedal edema ) with gastroenteritis (>3 loose stools per day) and signs of severe dehydration were included.”
The baseline table reports sex, age, weight, and many clinical and laboratory variables. Both sexes are included, so sex justification is not applicable. Demographics are reported for the trial population.
“Sex - male | 62 (45%) | 64 (48%) | 28 (42%) | 36 (54%)”
“Age months | 12 (9, 22) | 14 (9, 23) | 16 (9, 24) | 14 (9, 22)”
“Weight (kg) | 5.3 (4.5, 6.1) | 5.2 (4.6, 6.1) | 5.0 (4.5, 6.1) | 5.3 (4.7, 6.1)”
“Sex - male | 62 (45%) | 64 (48%) | 28 (42%) | 36 (54%)”
“Age months | 12 (9, 22) | 14 (9, 23) | 16 (9, 24) | 14 (9, 22)”
“Severe hyponatremia (sodium <125 mmol/L) | 70/131 (53%) | 67/131 (51%) | 35/66 (53%) | 32/65 (49%)”
The protocol was approved by local ethics committees. Informed consent was obtained, with provisions for verbal assent and delayed written consent when needed. Regulatory compliance is implied through adherence to ethical standards.
“The protocol was approved by the local ethics committees and is available at nejm.org (https://www.nejm.org/) .”
“When prior written consent from parents or legal guardians could not be obtained, ethics committees approved verbal assent with delayed written informed consent as soon as practical . Otherwise, written informed consent was obtained from parents or guardians before randomization.”
“When prior written consent from parents or legal guardians could not be obtained, ethics committees approved verbal assent with delayed written informed consent as soon as practical . Otherwise, written informed consent was obtained from parents or guardians before randomization.”
The trial uses Ringer's Lactate and oral rehydration solutions (ReSoMal and WHO ORS) as key resources, which are identified by name. Statistical software (Stata v18) is identified. No antibodies, cell lines, or other bench reagents are used.
“liberal:rapid rehydration (WHO Plan C: 100 ml/kg Ringer’s Lactate over 3-6 hours according to age with boluses (20 ml/kg) for those with shock)”
“all participants were simultaneously factorially randomized (1:1) either to ( Re hydration So lution for Mal nutrition (ReSoMal)) or WHO oral rehydration solution (ORS)”
“Analyses used Stata v18.”
“liberal:rapid rehydration (WHO Plan C: 100 ml/kg Ringer’s Lactate over 3-6 hours according to age with boluses (20 ml/kg) for those with shock) or liberal:slow rehydration (100 ml/kg Ringer’s Lactate over 8h and no boluses)”
“Analyses used Stata v18.”
The primary analysis uses Mantel-Haenszel adjusted risk ratio, Cox regression for secondary outcomes, and linear/logistic regression for continuous and binary outcomes. Exact p-values are reported for the primary endpoint. Effect sizes are reported with confidence intervals. Software is identified. Data presentation includes per-group n and appropriate measures.
“Randomized groups were compared with an intention-to-treat analysis using a Mantel-Haenszel adjusted risk ratio for mortality at 96hours (primary endpoint), adjusted for pre-specified covariate of site (hospital), and Cox regression for mortality by 28 days (secondary endpoint).”
“Adjusted Risk Ratio (aRR) (liberal vs. control) =1.02 (95% CI 0.41,2.52); p=0.69”
“Mortality at 96 hours | 11/138 (8%) | 9/134 (7%) | 5/67 (7%) | 4/67 (6%) | 1.02 (0.41,2.52) ; p=0.69”
“Randomized groups were compared with an intention-to-treat analysis using a Mantel-Haenszel adjusted risk ratio for mortality at 96hours (primary endpoint), adjusted for pre-specified covariate of site (hospital), and Cox regression for mortality by 28 days (secondary endpoint).”
“Adjusted Risk Ratio (aRR) (liberal vs. control) =1.02 (95% CI 0.41,2.52); p=0.69”
“Mortality at 96 hours | 11/138 (8%) | 9/134 (7%) | 5/67 (7%) | 4/67 (6%) | 1.02 (0.41,2.52) ; p=0.69”
The paper states that the protocol is available at NEJM.org, but does not provide a clear data availability statement for the trial data. No repository deposit or accession numbers are mentioned. Code sharing is not applicable as no custom code is described.
“The protocol was approved by the local ethics committees and is available at nejm.org (https://www.nejm.org/) .”
“The protocol was approved by the local ethics committees and is available at nejm.org (https://www.nejm.org/) .”
The trial is registered (ISRCTN76149273). Methods are detailed enough for replication. Limitations are discussed, including lower-than-expected mortality and generalizability. Conclusions are cautious and proportional. Funding and COI are disclosed.
“GASTROSAM Current Controlled Trials number, ISRCTN76149273”
“The key limitation of our trial was the much lower overall mortality (9%) than we predicted from two small studies, which reported mortality at hospital discharge or 28 days as 68-82% , , at the high end compared with other observational data.”
“Funded by the Joint Global Health Trials Scheme of the United Kingdom’s Medical Research Council, the UK Department for International Development and Wellcome (Grant Number MR/R018502/1) and by Médecins Sans Frontières”
“GASTROSAM Current Controlled Trials number, ISRCTN76149273”
“The key limitation of our trial was the much lower overall mortality (9%) than we predicted from two small studies, which reported mortality at hospital discharge or 28 days as 68-82%”
“Funded by the Joint Global Health Trials Scheme of the United Kingdom’s Medical Research Council, the UK Department for International Development and Wellcome (Grant Number MR/R018502/1) and by Médecins Sans Frontières”
Registered (1 ID: ISRCTN). No reporting guideline cited.
Broken references and links
None found · partly checkedReferences 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.
Nothing surfaced — but not everything feeding this category ran (missing: data/code link verification), so read this as a partial clean bill.
Checked 24 references by DOI: 19 verified — 5 no DOI (shown, not verified).
- NO DOIJoint child malnutrition estimatesNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIThe persistent global burden of severe acute malnutrition: cross-country estimates, models and forecastsNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIPocket book of hospital care for children Guidelines for the management of common childhood illnessesNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIGuidelines for the inpatient treatment of severely malnourished childrenNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
- NO DOIManagement of the child with a serious infection or severe malnutrition: guidelines for care at the first-referral level in developing countriesNo DOI in the reference — shown for manual review; not independently verifiable (not a fabrication signal).
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, typo, grammar.
- MINORtypoAbstract, Results“Risk Ratio=1.02(9 CI 0.38-2.39)”→ Change to 'Risk Ratio=1.02 (95% CI 0.38-2.39)'Missing '5' in '95% CI' and inconsistent spacing.
- MINORconsistencyAbstract vs. Results“Risk Ratio=1.02(9 CI 0.38-2.39) vs. aRR=1.02 (95% CI 0.41,2.52)”→ Ensure consistent reporting of the primary outcome estimate across abstract and results.The CI values differ between abstract and results; should be reconciled.
- MINORtypoMethods, Trial Design and Oversight“detailed in .”→ Add reference or remove placeholder.Incomplete sentence.
- MINORgrammarMethods, Trial Population“with at least bilateral pedal edema )”→ Remove extra space before parenthesis.Minor formatting.
- MINORconsistencyTable 2 footnote“¥ Columns show median (IQR) or n/N (%)”→ Use consistent symbols for footnotes.Symbol '¥' is unusual; consider using standard symbols.
- MINORconsistencyResults, Mortality“aRR=1.02 (95% CI 0.41,2.52)”→ Ensure consistent use of comma vs. period in CI ranges.Abstract uses 0.38-2.39, results use 0.41,2.52; likely different analyses but should be consistent.
The published work is robust and generally well-reported, but an informed reader should weigh the lack of a clear data availability statement and the minor internal inconsistency in the primary outcome CI between the abstract and results. These issues do not invalidate the findings but warrant attention; a correction or clarification would strengthen the record.
- 1.HIGHdata codeAdd a clear data availability statement in the Methods or a dedicated section, specifying how de-identified participant data can be accessed (e.g., via a data access committee or repository) and any conditions.The current statement only mentions the protocol availability, not the data, which is a transparency gap for a data-driven trial.
- 2.HIGHdata codeDeposit de-identified participant data in a public repository (e.g., ClinicalStudyDataRequest, Vivli) with a DOI or accession number.Repository deposit enhances reproducibility and is expected for clinical trials.
- 3.HIGHstatisticsReconcile the primary outcome confidence interval reported in the Abstract (0.38-2.39) with that in the Results (0.41,2.52) and ensure consistent reporting.The discrepancy between the abstract and results could confuse readers and may indicate an error in one of the analyses.
- 4.HIGHreportingTemper the recommendation to simplify rehydration protocols and remove the distinction between SAM and non-malnourished children, as it goes beyond the direct evidence of the trial.The trial found no difference in mortality, but the claim to change guidance is based on absence of harm and operational simplicity, which is an overstatement.
- 5.MEDIUMreportingExplicitly state adherence to a reporting guideline such as CONSORT in the Methods or provide a CONSORT flow diagram and checklist.Explicit reporting guideline adherence improves transparency and is a common expectation for RCTs.
- 6.MEDIUMethicsName the specific ethics committees that approved the protocol and include protocol numbers.Specific committee names and protocol numbers strengthen the ethics documentation.
- 7.MEDIUMethicsState compliance with the Declaration of Helsinki or other regulatory framework.Explicit regulatory compliance is a standard expectation for human research.
- 8.MEDIUMdata codeConsider depositing the statistical analysis code in a public repository for reproducibility.Sharing analysis code allows independent verification of the statistical methods.
- 9.LOWcopyeditFix the typo in the Abstract: change 'Risk Ratio=1.02(9 CI 0.38-2.39)' to 'Risk Ratio=1.02 (95% CI 0.38-2.39)'.The missing '5' in '95% CI' and inconsistent spacing are minor but should be corrected.
- 10.LOWcopyeditComplete the incomplete sentence in Methods, Trial Design and Oversight: 'detailed in .'The placeholder should be replaced with a reference or removed.
- 11.LOWcopyeditRemove the extra space before the parenthesis in Methods, Trial Population: 'with at least bilateral pedal edema )'.Minor formatting issue.
- 12.LOWcopyeditUse consistent symbols for footnotes in Table 2, replacing the unusual '¥' with standard symbols.Consistent footnote symbols improve readability.
- 13.LOWcopyeditEnsure consistent use of comma vs. period in CI ranges across the manuscript.The abstract uses 0.38-2.39 while results use 0.41,2.52; consistency is needed.
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.