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Clinical Neurology and Neurosurgery Apr 2023Intracerebral hemorrhage (ICH) is a stroke with a high morbidity and mortality rate. Deferoxamine (DFX) is thought to be effective in treating Intracerebral Hemorrhage.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Intracerebral hemorrhage (ICH) is a stroke with a high morbidity and mortality rate. Deferoxamine (DFX) is thought to be effective in treating Intracerebral Hemorrhage. In our study, we performed a meta-analysis to evaluate the treatment effects of DFX.
METHODS
We systematically searched PubMed, Embase, Web of Science, the Cochrane Central Register of Controlled Trials, and Chinese Biomedical Literature Database in Jan 2022 for studies on DFX for ICH patients. Outcome measures included relative hematoma volume, relative edema volume, good neurological functional outcome and adverse events. Odds risk (OR) and weighted mean difference (WMD) were used to evaluate clinical outcomes.
RESULTS
After searching 636 articles, 4 RCTs, 2 NRCTs, and 1cohort study were included. We found that DFX was effective in hematoma absorption on day 7 after onset, but the difference was not significant on day 14. DFX could suppress edema expansion on days 3, 7, and 14 after onset. DFX did not contribute to better outcomes after 3 and 6 months when used the modified Rankin Scale and the Glasgow Outcome Scale to evaluate neurological prognosis. The pooled results showed no statistically significant difference in Serious adverse events between the experimental and control groups.
CONCLUSIONS
DFX could limit edema expansion on days 3, 7, and 14 after commencement and facilitate hematoma absorption at week 1 without significantly increasing the risk of adverse events, but it did not improve neurological prognosis.
Topics: Humans; Deferoxamine; Siderophores; Cerebral Hemorrhage; Stroke; Hematoma
PubMed: 36857886
DOI: 10.1016/j.clineuro.2023.107634 -
PloS One 2018Intracerebral hemorrhage (ICH) is a significant cause of morbidity and mortality worldwide. Several recent controlled trials have reported that deferoxamine (DFX)... (Review)
Review
Intracerebral hemorrhage (ICH) is a significant cause of morbidity and mortality worldwide. Several recent controlled trials have reported that deferoxamine (DFX) therapy appears to be effective for ICH. The aim of this study was to perform a systematic review of DFX therapy for ICH patients and evaluate the efficacy and safety of DFX therapy for ICH patients. We searched Medline, Embase, the Cochrane Database of Systematic Reviews, clinicaltrials.gov, all Chinese databases and the reference lists of all included studies and review articles. We then performed a systematic review of studies involving the administration of DFX following ICH. Only two studies were included, a prospective, randomized clinical trial and a prospective,observational cohort study with concurrent groups. Qualitative analysis of each study revealed one randomized controlled trial of moderate quality with a moderate risk of bias and one observational cohort study of moderate quality with a moderate risk of bias. DFX may be an effective treatment for edema in patients with ICH. However, due to the small number of trials and small sample sizes of these trials, insufficient evidence exists to determine the effect of DFX on neurologic outcomes after ICH and the safety of this intervention. Further investigation is required before DFX can become a routine treatment for ICH.
Topics: Cerebral Hemorrhage; Deferoxamine; Humans
PubMed: 29566000
DOI: 10.1371/journal.pone.0193615 -
Caspian Journal of Internal Medicine 2017Hearing disorders are reported in thalassemia patients treated with deferoxamine. This study aimed to assess hearing loss in Iranian thalassemia major patients treated... (Review)
Review
BACKGROUND
Hearing disorders are reported in thalassemia patients treated with deferoxamine. This study aimed to assess hearing loss in Iranian thalassemia major patients treated with deferoxamine.
METHODS
This review article was designed based on PRISMA guidelines. To review the literature, two researchers studied national and international databases including Iranmedex, Magiran, Medlib, SID, Scopus, PubMed, Science Direct, Web of Science and Google Scholar without time limit until May 2017. Cochran's Q test and I index were used to assess the heterogeneity of the studies. The data were analyzed using Comprehensive Meta-Analysis software version 2 and p<0.05 was considered significant.
RESULTS
A total of 17 articles involving 1,835 Iranian thalassemia major patients treated with deferoxamine were included in the meta-analysis. The overall prevalence of hearing loss was estimated 27.3% (95% confidence intervals (CI): 19-37.6). The prevalence of sensorineural, conductive and mixed hearing loss was estimated 10.6% (95% CI: 5.7-18.8), 14.6% (95% CI: 10.5-20.6) and 9.1% (95% CI: 5.6-14.6), respectively. No significant differences were noted regarding the relationship hearing loss and mean serum ferritin (P=0.29) and average daily deferoxamine (P=0.30). Meta-regression model showed an increased significance in the prevalence of hearing loss based on the year of studies (p<0.0001).
CONCLUSIONS
There is a high prevalence of hearing loss in Iranian thalassemia major patients treated with deferoxamine. Therefore, periodic hearing assessments and regular check-ups after the initiation of chelation therapy are necessary.
PubMed: 29201313
DOI: 10.22088/cjim.8.4.239 -
Hemoglobin 2014β-Thalassemia major (β-TM) patients require life-long blood transfusions, resulting in iron overload with multi-organ morbidity and mortality. Evidence from small... (Meta-Analysis)
Meta-Analysis Review
A systematic review and meta-analysis of deferiprone monotherapy and in combination with deferoxamine for reduction of iron overload in chronically transfused patients with β-thalassemia.
β-Thalassemia major (β-TM) patients require life-long blood transfusions, resulting in iron overload with multi-organ morbidity and mortality. Evidence from small randomized controlled trials (RCTs) published to date for deferiprone (DFP) monotherapy or in combination with deferoxamine (DFO) is unclear. We summarized evidence on the efficacy of DFP monotherapy compared to DFO, and DFP-DFO combination therapy compared to DFP or DFO monotherapy in chronically transfused β-TM. We searched four electronic databases and examined the grey literature. Two authors independently assessed trial quality and extracted data. We calculated the relative risk for dichotomous outcomes and mean difference (MD) for continuous outcomes. We identified 15 RCTs (1003 participants) that met the inclusion criteria. Deferiprone was more efficacious than DFO in improving cardiac ejection fraction [MD 2.88, 95% CI (95% confidence interval) 1.12 to 4.64, p = 0.001) and endocrine dysfunction (MD 0.09, 95% CI 0.08 to 0.10, p < 0.00001). The DFP-DFO combination therapy was more efficacious than DFP or DFO monotherapy in improving cardiac ejection fraction (MD 5.67, 95% CI 1.32 to 10.02, p = 0.008). There was no significant difference in all other outcomes examined. Meta-analysis on changes in myocardial iron content was not possible due to differences in data presentation. The quality of evidence for all outcomes was low. There is currently insufficient evidence to show that DFP is superior to DFO in the treatment of iron overload. The use of DFP must be weighed against the potential side-effects, patient compliance and preference. Large RCTs with clinically relevant outcomes are required.
Topics: Blood Transfusion; Deferiprone; Deferoxamine; Female; Humans; Iron Chelating Agents; Iron Overload; Male; Pyridones; beta-Thalassemia
PubMed: 25307964
DOI: 10.3109/03630269.2014.965781 -
Cureus Nov 2023Despite the established efficacy of iron chelation therapy in transfusion-induced iron-overloaded patients, there is no universal agreement regarding the choice of an... (Review)
Review
Despite the established efficacy of iron chelation therapy in transfusion-induced iron-overloaded patients, there is no universal agreement regarding the choice of an optimal chelating regimen. Deferasirox (DFX) and deferiprone (DFP) are two oral iron chelators, and combination usage demonstrated effectiveness as an alternative to monotherapies in patients with a limited response to monotherapy. The present systematic review aimed to assess the evidence regarding the outcomes of combined DFP and DFX in iron-overloaded patients. An online search was conducted in PubMed, Scopus, Web of Science, and CENTRAL databases. Interventional and observational studies that assessed the outcomes of combined DFP and DFX in iron-overloaded patients were included. Eleven studies (12 reports) were considered in this meta-analysis. The studies included dual iron chelation strategies for a number of diagnoses. Single-arm studies (n =7) showed a reduction of serum ferritin, which reached the level of statistical significance in three studies. Likewise, most studies reported a numerical reduction in liver iron concentration (LIC) and increased cardiac MRI-T2* values after chelating therapy. Alternatively, comparative studies showed no significant difference in post-treatment serum ferritin between DFX plus DFP and DFX/DFP plus deferoxamine (DFO). The adherence to combination therapy was good to average in nearly 66.7-100% of the patients across four studies. One study reported a poor adherence rate. The combined regimen was generally tolerable, with no reported incidence of serious adverse events among the included studies. In conclusion, the DFP and DFX combination is a safe and feasible option for iron overload patients with a limited response to monotherapy.
PubMed: 38058350
DOI: 10.7759/cureus.48276 -
PloS One 2015Intracerebral hemorrhage (ICH) is a subtype of stroke associated with high morbidity and mortality rates. No proven treatments are available for this condition.... (Review)
Review
Intracerebral hemorrhage (ICH) is a subtype of stroke associated with high morbidity and mortality rates. No proven treatments are available for this condition. Iron-mediated free radical injury is associated with secondary damage following ICH. Deferoxamine (DFX), a ferric-iron chelator, is a candidate drug for the treatment of ICH. We performed a systematic review of studies involving the administration of DFX following ICH. In total, 20 studies were identified that described the efficacy of DFX in animal models of ICH and assessed changes in the brain water content, neurobehavioral score, or both. DFX reduced the brain water content by 85.7% in animal models of ICH (-0.86, 95% CI: -.48- -0.23; P < 0.01; 23 comparisons), and improved the neurobehavioral score by -1.08 (95% CI: -1.23- -0.92; P < 0.01; 62 comparisons). DFX was most efficacious when administered 2-4 h after ICH at a dose of 10-50 mg/kg depending on species, and this beneficial effect remained for up to 24 h postinjury. The efficacy was higher with phenobarbital anesthesia, intramuscular injection, and lysed erythrocyte infusion, and in Fischer 344 rats or aged animals. Overall, although DFX was found to be effective in experimental ICH, additional confirmation is needed due to possible publication bias, poor study quality, and the limited number of studies conducting clinical trials.
Topics: Animals; Cerebral Hemorrhage; Deferoxamine; Disease Models, Animal; Mice; Rats; Siderophores; Swine; Treatment Outcome
PubMed: 26000830
DOI: 10.1371/journal.pone.0127256 -
Cardiovascular Drugs and Therapy Apr 2014Coronary reperfusion by primary percutaneous coronary intervention (PCI) has been established as an essential therapy of ST-elevation myocardial infarction (STEMI).... (Review)
Review
PURPOSE
Coronary reperfusion by primary percutaneous coronary intervention (PCI) has been established as an essential therapy of ST-elevation myocardial infarction (STEMI). Although the coronary intervention is undoubtedly beneficial, reperfusion itself can induce processes resulting in additional myocardial damage-a phenomenon known as ischemia-reperfusion injury (IRI). Oxidative stress is one of the major factors contributing to IRI. This systematic review focuses on the effect of antioxidant therapy on reperfusion triggered oxidative stress and myocardial IRI in patients with STEMI.
METHODS
We performed a systematic search in EMBASE and Pubmed and included eight randomised clinical trials evaluating edaravone, allopurinol, vitamin c, nicorandil, N-acetylcysteine, glucose-insulin-potassium, atorvastatin and deferoxamine.
RESULTS
Administration of edaravone, allopurinol, atorvastatin and nicorandil as a supplement to primary PCI significantly reduced oxidative stress and myocardial damage as well as improved cardiac function and clinical outcomes. Treatment with deferoxamine and N-acetylcysteine reduced the oxidative stress but an effect on the clinical outcome parameters could not be shown.
CONCLUSIONS
Preliminary studies of edaravone, allopurinol, atorvastatin and nicorandil seems promising though larger clinical trials with a wider range of clinical outcome parameters and trials of higher methodological quality should confirm the clinical benefits before a general recommendation can be given. Moreover, the included studies revealed a complex link between oxidative stress and cardiac function and/or cardiac adverse events and in order to further elucidate the detrimental role of oxidative stress in IRI in relation to primary PCI the assessment of oxidative stress and the clinical outcome parameters should be standardized.
Topics: Antioxidants; Humans; Myocardial Infarction; Myocardial Reperfusion; Myocardium; Oxidative Stress; Percutaneous Coronary Intervention; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 24532094
DOI: 10.1007/s10557-014-6511-3 -
British Journal of Haematology Jun 2008Iron chelators have dramatically prolonged the life expectancy of patients with transfusion-dependent thalassaemia, but their precise clinical benefit in reducing the... (Review)
Review
Iron chelators have dramatically prolonged the life expectancy of patients with transfusion-dependent thalassaemia, but their precise clinical benefit in reducing the myocardial iron burden and improving cardiac function is unknown. This systematic review and meta-analysis included published clinical trials that assessed the efficacy of iron chelators in regularly transfused patients of thalassaemia major for two commonly reported outcomes - myocardial iron content and left ventricular ejection fraction (LVEF). The meta-analysis of 392 patients for myocardial iron content and 291 patients for LVEF showed that (i) iron chelators reduced cardiac iron content by 23.9% (95% confidence interval 17.3-29.8%); (ii) there was no significant difference between the amount of iron reduced by deferoxamine and deferiprone (P = 0.9504); and (iii) LVEF was not significantly influenced by iron chelators - summary Hedge's g 0.13 (95% confidence interval -0.10-0.36). A significant publication bias existed for LVEF (Egger's P = 0.049) but not for myocardial iron (Egger's P = 0.871). Our results indicate that iron chelators significantly reduce myocardial iron content. Further, the choice of deferoxamine versus deferiprone may rest on factors other than their efficacy to reduce cardiac iron load.
Topics: Blood Transfusion; Chelation Therapy; Humans; Iron; Iron Chelating Agents; Magnetic Resonance Imaging; Myocardium; Publication Bias; Stroke Volume; Thalassemia; Ventricular Function, Left
PubMed: 18355381
DOI: 10.1111/j.1365-2141.2008.07122.x -
The Journal of International Medical... Dec 2022To examine the efficacy of deferasirox (DFX) by comparison with deferoxamine (DFO) in managing iron overload in patients with sickle cell anaemia (SCA). (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To examine the efficacy of deferasirox (DFX) by comparison with deferoxamine (DFO) in managing iron overload in patients with sickle cell anaemia (SCA).
METHODS
Online databases were systematically searched for studies published from January 2007 to July 2022 that had investigated the efficacy of DFX compared with DFO in managing iron overload in patients with SCA.
RESULTS
Of the 316 articles identified, three randomized clinical trials met the inclusion criteria. Meta-analysis of liver tissue iron concentration (LIC) showed that iron overload was not significantly higher in the DFX group compared with DFO group (WMD, -1.61 mg Fe/g dw (95% CI -4.42 to 1.21). However, iron overload as measured by serum ferritin was significantly lower in DFO compared with DFX group (WMD, 278.13 µg/l (95% CI 36.69 to 519.57). Although meta-analysis was not performed on myocardial iron concentration due to incomplete data, the original report found no significant difference between DFX and DFO.
CONCLUSION
While limited by the number of studies included in this meta-analysis, overall, the results tend to show that DFX was as effective as DFO in managing iron overload in patients with SCA.
Topics: Humans; Deferasirox; Deferoxamine; Iron Chelating Agents; Benzoates; Triazoles; Iron Overload; Iron; Anemia, Sickle Cell
PubMed: 36562113
DOI: 10.1177/03000605221143290 -
The Cochrane Database of Systematic... Aug 2010Sickle cell disease (SCD) is a group of genetic haemoglobin disorders. Increasingly, some people with SCD develop secondary iron overload due to occasional red blood... (Review)
Review
BACKGROUND
Sickle cell disease (SCD) is a group of genetic haemoglobin disorders. Increasingly, some people with SCD develop secondary iron overload due to occasional red blood cell transfusions or are on long-term transfusion programmes for e.g. secondary stroke prevention. Iron chelation therapy can prevent long-term complications.Deferoxamine and deferiprone have been found to be efficacious. However, questions exist about the effectiveness and safety of the new oral chelator deferasirox.
OBJECTIVES
To assess the effectiveness and safety of oral deferasirox in people with SCD and secondary iron overload.
SEARCH STRATEGY
We searched the Cystic Fibrosis & Genetic Disorders Group's Haemoglobinopathies Trials Register (06 April 2010).We searched MEDLINE, EMBASE, EBMR, Biosis Previews, Web of Science, Derwent Drug File, XTOXLINE and three trial registries: www.controlled-trials.com; www.clinicaltrials.gov; www.who.int./ictrp/en/. Most recent searches: 22 June 2009.
SELECTION CRITERIA
Randomised controlled trials comparing deferasirox with no therapy or placebo or with another iron chelating treatment schedule.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed study quality and extracted data. We contacted the study author for additional information.
MAIN RESULTS
One study (203 people) was included comparing the efficacy and safety of deferasirox and deferoxamine after 12 months. Data were not available on mortality or end-organ damage. Using a pre-specified dosing algorithm serum ferritin reduction was similar in both groups, mean difference (MD) 375.00 microg/l in favour of deferoxamine; (95% confidence interval (CI) -106.08 to 856.08). Liver iron concentration measured by superconduction quantum interference device showed no difference for the overall group of patients adjusted for transfusion category, MD -0.20 mg Fe/g dry weight (95% CI -3.15 to 2.75).Mild stable increases in creatine were observed more often in people treated with deferasirox, risk ratio 1.64 (95% CI 0.98 to 2.74). Abdominal pain and diarrhoea occurred significantly more often in people treated with deferasirox. Rare adverse events (less than 5% increase) were not reported; long-term adverse events could not be measured in the included study (follow-up 52 weeks). Patient satisfaction with, and convenience of treatment were significantly better with deferasirox.
AUTHORS' CONCLUSIONS
Deferasirox appears to be as effective as deferoxamine. However, only limited evidence is available assessing the efficacy regarding patient-important outcomes. The short-term safety of deferasirox seems to be acceptable, however, follow-up was too short to exclude long-term side effects and thus treatment with deferasirox cannot be judged completely safe. Future studies should assess long-term outcomes for safety and efficacy, and also evaluate rarer adverse effects.
Topics: Anemia, Sickle Cell; Benzoates; Chelation Therapy; Deferasirox; Deferoxamine; Erythrocyte Transfusion; Ferritins; Humans; Iron Chelating Agents; Iron Overload; Randomized Controlled Trials as Topic; Triazoles
PubMed: 20687088
DOI: 10.1002/14651858.CD007477.pub2