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. 2020 Nov 24;11(11):CD009280.
doi: 10.1002/14651858.CD009280.pub3.

Iron chelators for acute stroke

Lars E Van der Loo  1 , René Aquarius  2 , Onno Teernstra  1 , Karin Klijn  3 , Tomas Menovsky  4 , J Marc C van Dijk  5 , Ronald Bartels  2 , Hieronymus Damianus Boogaarts  6
Affiliations

Iron chelators for acute stroke

Lars E Van der Loo et al. Cochrane Database Syst Rev. .

Abstract

Background: Stroke is the second leading cause of death and a major cause of morbidity worldwide. Retrospective clinical and animal studies have demonstrated neuroprotective effects of iron chelators in people with haemorrhagic or ischaemic stroke. This is the first update of the original Cochrane Review published in 2012.

Objectives: To evaluate the effectiveness and safety of iron-chelating drugs in people with acute stroke.

Search methods: We searched the Cochrane Stroke Group Trials Register (2 September 2019), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2019, Issue 9; 2 September 2019), MEDLINE Ovid (2 September 2019), Embase Ovid (2 September 2019), and Science Citation Index (2 September 2019). We also searched ongoing trials registers.

Selection criteria: We included randomised controlled trials (RCTs) of iron chelators versus no iron chelators or placebo for the treatment of acute stroke, including subarachnoid haemorrhage.

Data collection and analysis: Two review authors independently screened the search results. We obtained the full texts of potentially relevant studies and evaluated them for eligibility. We assessed risk of bias using the Cochrane 'Risk of bias' tool, and the certainty of evidence using the GRADE approach.

Main results: Two RCTs (333 participants) were eligible for inclusion; both compared the iron-chelating agent deferoxamine against placebo. Both studies evaluated participants with spontaneous intracerebral haemorrhage. We assessed one study to have a low risk of bias; the other study had potential sources of bias. The limited and heterogeneous data did not allow for meta-analysis of the outcome parameters. The evidence suggests that administration of deferoxamine may result in little to no difference in deaths (8% in placebo vs 8% in deferoxamine at 180 days; 1 RCT, 291 participants; low-certainty evidence). These RCTs suggest that there may be little to no difference in good functional outcome (modified Rankin Scale score 0 to 2) between groups at 30, 90 and 180 days (placebo vs deferoxamine: 67% vs 57% at 30 days and 36% vs 45% at 180 days; 2 RCTs, 333 participants; low-certainty evidence). One RCT suggests that administration of deferoxamine may not increase the number of serious adverse events or deaths (placebo vs deferoxamine: 33% vs 27% at 180 days; risk ratio 0.81, 95 % confidence interval 0.57 to 1.16; 1 RCT, 291 participants; low-certainty evidence). No data were available on any deaths within the treatment period. Deferoxamine may result in little to no difference in the evolution of National Institute of Health Stroke Scale scores from baseline to 90 days (placebo vs deferoxamine: 13 to 4 vs 13 to 3; P = 0.37; 2 RCTs, 333 participants; low-certainty evidence). Deferoxamine may slightly reduce relative oedema surrounding intracerebral haemorrhage at 15 days (placebo vs deferoxamine: 1.91 vs 10.26; P = 0.042; 2 RCTs, 333 participants; low-certainty evidence). Neither study reported quality of life.

Authors' conclusions: We identified two eligible RCTs for assessment. We could not demonstrate any benefit for the use of iron chelators in spontaneous intracerebral haemorrhage. The added value of iron-chelating therapy in people with ischaemic stroke or subarachnoid haemorrhage remains unknown.

Trial registration: ClinicalTrials.gov NCT00777140 NCT02216513 NCT02875262 NCT03754725.

PubMed Disclaimer

Conflict of interest statement

Lars van der Loo: none known.

René Aquarius: none known.

Onno Teernstra: none known.

Karin Klijn: none known.

Thomas Menovsky: none known.

Marc van Dijk: none known.

Ronald Bartels: none known.

Hieronymus Boogaarts: none known.

Figures

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1
Study flow diagram
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Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across the included studies
3
3
Risk of bias summary: review authors' judgements about each risk of bias item for each included study
See this image and copyright information in PMC

Update of

References

References to studies included in this review

Selim 2019 {published data only}
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ChiCTR‐TRC‐14004979 {unpublished data only}ChiCTR‐TRC‐14004979
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EUCTR2007‐006731‐31‐ES {unpublished data only}EUCTR2007‐006731‐31‐ES
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IRCT2013111915444N2 {unpublished data only}IRCT2013111915444N2
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NCT02216513 {unpublished data only}
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NCT02875262 {unpublished data only}
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NCT03754725 {unpublished data only}
    1. NCT03754725. Deferiprone for ruptured brain aneurysm. clinicaltrials.gov/ct2/show/NCT03754725 (first received 27 November 2018).

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