CHAMGAP
APPROVEDReviewed and approved by the Chamgap Editorial Team (2026-08-18). The draft was written by AI, the existence of all 2 cited sources was verified at the original page, and the verdict passed blind grading and adversarial audit. Methodology v0.7.
Verdict No. 2786 · Search date 2026-08-18 · Methodology v0.7

Delayed sodium thiosulfate,
does it really help with Prevention of cisplatin-induced hearing loss in children?

30-Second Summary
C
Evidence Grade C · 50 · Safety warning
Two pediatric phase 3 trials substantially reduced hearing loss, but disseminated disease carries a survival concern
SIOPEL-6 reported sodium-thiosulfate-related serious reactions including metabolic acidosis. A post hoc disseminated-disease subgroup in ACCL0431 had significantly worse three-year overall survival, requiring major caution in that population.
What the
research shows
The grade is C. In SIOPEL-6 for standard-risk hepatoblastoma, hearing loss occurred in 18/55 (33%) with sodium thiosulfate versus 29/46 (63%) with cisplatin alone, RR 0.52, 95% CI 0.33 to 0.81. The 30-point absolute reduction corresponds to about one case prevented per 3.3 treated children. ACCL0431 replicated the direction, 14/49 (28.6%) versus 31/55 (56.4%). The endpoints were audiometry-based, both trials enrolled fewer than 200 participants, and the company supplied study drug, giving C with 50 points.
What the
ads claim
Marketing should not translate the risk ratio into a vague claim that hearing is protected by nearly one half. The standard-risk hepatoblastoma trial reduced hearing loss from 63% to 33%, an absolute 30-point difference, under a specific six-hour delayed schedule.
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Useful facts when choosing a product

  • SIOPEL-6 administered sodium thiosulfate 20 g/m² intravenously over 15 minutes, six hours after cisplatin ended.
  • The Fennec-supplied item was the intervention drug, not an assessment tool.
  • ACCL0431 replicated hearing protection across pediatric cancers but raised a survival concern in disseminated disease.
Gap Measurement · Verdict 2786 · C 50
What advertising claims
What independent, higher-quality research supports
△ GAP
01

What the research actually shows

SIOPEL-6 randomized 113 children at 52 centers in 12 countries; after four ineligible participants were removed, 109 entered the intention-to-treat population and 101 were evaluable for hearing. Its protocol assumed a reduction from 60% to 35%, requiring 102 evaluable and 115 enrolled participants; the observed absolute reduction was 30 points. ACCL0431 randomized 125, 61 versus 64, and used a modified intention-to-treat hearing analysis in 104, 49 versus 55. Both trials were open label, with centrally reviewed audiometry masked to allocation. Neither stopped early. SIOPEL-6 used Cancer Research UK and other public or charitable funding; ACCL0431 used US National Cancer Institute funding. Fennec Pharmaceuticals supplied the active study drug without charge in both trials. SIOPEL-6 also disclosed OHSU and US Department of Veterans Affairs financial interests in Fennec and an inventor relationship.

02

Why this is classified as C (50)

Both trials pointed the same way but **share a core investigator**, so they are not counted as independent replication; the primary endpoint is an audiometric surrogate and funding is mixed, giving C with 50 points.

Counterpoint. C does not mean the effect was small. It reflects the evidence structure and restricted safe application despite a large hearing-loss reduction in localized pediatric cancer.

Rejudgment record. Cross-check applied — Cross-checks hearing denominators and results, public funding, Fennec study-drug supply, and disease-extent survival findings in SIOPEL-6 and ACCL0431

Scoring profile behind this grade
EndpointSSurrogate marker - laboratory or imaging measures
ReplicationR1Single confirmatory trial
IndependenceI1Mixed funding sources
Effect sizeE+Meets the clinically important threshold

The scoring table and the verdict agree (C).

Sub-claim grades by effect

This ingredient is marketed for several effects. A single overall grade blends strong and weak claims together, so each effect is graded separately here. The overall grade reflects the strongest disconfirming or core claim.

Effect (sub-claim)GradeBasis
Reduced cisplatin hearing loss in localized pediatric cancerCTwo phase 3 trials replicated an absolute reduction of about 28 to 30 points.
Use in disseminated cancer without compromising survivalDA post hoc ACCL0431 subgroup had significantly worse overall survival.

Cross-check — Codex and Claude

This verdict was drafted by Codex through literature review and source-existence checks, cross-checked through blind grading and adversarial audit, and settled by reapplying the methodology boundary rules. Cases with split grades were resolved through rejudgment.
03

Evidence Table

StudyDesignSampleFundingEndpointResultWeight
Study 1International open-label randomized phase 3 trial with central hearing review46Public and charitable funding including Cancer Research UK; Fennec supplied study drug without chargeCisplatin hearing loss of Brock grade 1 or higher18/55 (33%) versus 29/46 (63%), RR 0.52, 95% CI 0.33 to 0.81, absolute difference -30 pointsPivotal phase 3 evidence in standard-risk hepatoblastoma
Study 2Multicenter open-label randomized phase 3 trial with allocation-masked central hearing review55US National Cancer Institute public funding; Fennec supplied study drug without chargeASHA-defined hearing loss four weeks after final cisplatin14/49 (28.6%) versus 31/55 (56.4%), adjusted OR 0.31, 95% CI 0.13 to 0.73Replication by a separate team, with a disseminated-disease survival concern
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Receipt — 2 References

All 2 cited sources were verified for existence at the original page (as of 2026-08-18).

Brock PR, Maibach R, Childs M, et al. Sodium Thiosulfate for Protection from Cisplatin-Induced Hearing Loss. N Engl J Med. 2018;378(25):2376-2385. PMID: 29924955. DOI: 10.1056/NEJMoa1801109.
checked
Freyer DR, Chen L, Krailo MD, et al. Effects of sodium thiosulfate versus observation on development of cisplatin-induced hearing loss in children with cancer (ACCL0431). Lancet Oncol. 2017;18(1):63-74. PMID: 27914822. DOI: 10.1016/S1470-2045(16)30625-8.
checked
Draft and rewrite: Codex (AI) · Verification: Codex blind grading and adversarial audit · Final adjudication: Claude
Reviewed and approved: Chamgap Editorial Team · Approval date: 2026-08-18 · Corrections: none

Cite this verdict

Delayed sodium thiosulfate x pediatric cisplatin-induced hearing loss Evidence Grade C card
[Chamgap] Delayed sodium thiosulfate x pediatric cisplatin-induced hearing loss — Evidence Grade C·50. 2 cited sources checked. Source: https://chamgap.com/en/verdicts/general/delayed-sodium-thiosulfate-pediatric-cisplatin-hearing-loss/ · CC BY 4.0

CC BY 4.0 — free to use with attribution; do not distort grades, numbers, or verdict meaning.

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