-
The Cochrane Database of Systematic... Jul 2007Thalassaemia major is a genetic disease characterised by a reduced ability to produce haemoglobin. Management of the resulting anaemia is through transfusions of red... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Thalassaemia major is a genetic disease characterised by a reduced ability to produce haemoglobin. Management of the resulting anaemia is through transfusions of red blood cells. Repeated transfusions result in excessive accumulation of iron in the body (iron overload), removal of which is achieved through iron chelation therapy. A commonly used iron chelator, deferiprone, has been found to be pharmacologically efficacious. However, important questions exist about the efficacy and safety of deferiprone compared to another iron chelator, desferrioxamine.
OBJECTIVES
To summarise data from trials on the clinical efficacy and safety of deferiprone and to compare the clinical efficacy and safety of deferiprone for thalassaemia with desferrioxamine.
SEARCH STRATEGY
We searched the Group's Haemoglobinopathies Trials Register, MEDLINE, EMBASE, Biological Abstracts, ZETOC, Current Controlled Trials and bibliographies of relevant publications. We contacted the manufacturers of deferiprone and desferrioxamine. Most recent searches: June 2006.
SELECTION CRITERIA
Randomised controlled trials comparing deferiprone with another iron chelator; or comparing two schedules of deferiprone, in people with transfusion-dependent thalassaemia.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed trial quality and extracted data. Missing data were requested from the original investigators.
MAIN RESULTS
Ten trials involving 398 people (range 10 to 144 people) were included. Nine trials compared deferiprone with desferrioxamine or a combination of deferiprone and desferrioxamine and one compared different schedules of deferiprone. There was little consistency between outcomes and little information to fully assess the methodological quality of most of the included trials. No trial reported long-term outcomes (mortality and end organ damage). There was no consistent effect on reduction of iron overload between all treatment comparisons, with the exception of urinary iron excretion in comparisons of deferiprone with desferrioxamine. An increase in iron excretion levels favoured deferiprone in one trial and desferrioxamine in three trials, even though measurement of urinary iron excretion underestimates total iron excretion by desferrioxamine.Adverse events were recorded in trials comparing deferiprone with desferrioxamine. There was evidence of adverse events in all treatment groups. Adverse events in one trial were significantly more likely with deferiprone than desferrioxamine, relative risk 2.24 (95% confidence interval 1.19 to 4.23).
AUTHORS' CONCLUSIONS
We found no reason to change current treatment recommendations, namely deferiprone is indicated for treating iron overload in people with thalassaemia major when desferrioxamine is contraindicated or inadequate. However, there is an urgent need for adequately-powered, high quality trials comparing the overall clinical efficacy and long-term outcome of deferiprone with desferrioxamine.
Topics: Chelation Therapy; Deferiprone; Deferoxamine; Humans; Iron Chelating Agents; Iron Overload; Pyridones; Randomized Controlled Trials as Topic; Thalassemia; Treatment Outcome
PubMed: 17636775
DOI: 10.1002/14651858.CD004839.pub2 -
Tropical Medicine & International... Nov 2005Randomized controlled clinical trials (RCTs) of adjunctive treatment to reduce the high-mortality associated with cerebral malaria (CM) have so far failed to show any... (Review)
Review
BACKGROUND
Randomized controlled clinical trials (RCTs) of adjunctive treatment to reduce the high-mortality associated with cerebral malaria (CM) have so far failed to show any benefit. This may be due in part to improperly designed and/or conducted trials. Therefore a systematic review of quality of RCTs for the treatment of CM with mortality as either primary or secondary outcome published between 1980 and 2000, was conducted.
METHODS
RCTs from the peer-reviewed literature using electronic searches. Methodological quality was assessed using an individual component approach (adequacy of concealment of allocation schedule, generation of allocation sequence, double blinding and analysis of participant as randomized). Sample sizes were recalculated for the ability of reviewed trials to detect 25% and 50% reductions in mortality.
RESULTS
Nine trials satisfied the inclusion criteria and were reviewed. Only two had sufficient power to detect a 50% reduction in mortality, and none could detect a 25% reduction. All the trials had inadequate methodological quality in one or more of the components, although in two trials these deficiencies were few.
CONCLUSION
There is a need for researchers and donors to ensure proper planning and implementation of RCTs in developing countries. In CM, demonstration of worthwhile reduction in mortality by a single intervention will require a large number of subjects, which a single centre may not be able to recruit.
Topics: Anticonvulsants; Deferoxamine; Dexamethasone; Double-Blind Method; Enzyme Inhibitors; Humans; Malaria, Cerebral; Pentoxifylline; Phenobarbital; Randomized Controlled Trials as Topic; Sample Size; Siderophores; Tumor Necrosis Factor-alpha
PubMed: 16262742
DOI: 10.1111/j.1365-3156.2005.01505.x -
The Cochrane Database of Systematic... Oct 2005Thalassaemia major is a genetic disease characterised by a reduced ability to produce haemoglobin. Management of the resulting anaemia is through transfusions of red... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Thalassaemia major is a genetic disease characterised by a reduced ability to produce haemoglobin. Management of the resulting anaemia is through transfusions of red blood cells. Repeated transfusions results in excessive accumulation of iron in the body (iron overload), removal of which is achieved through iron chelation therapy. Desferrioxamine is the most widely used iron chelator. Substantial data have shown the beneficial effects of desferrioxamine. However, important questions exist about whether desferrioxamine is the best schedule for iron chelation therapy.
OBJECTIVES
To determine the effectiveness (dose and method of administration) of desferrioxamine in people with transfusion-dependent thalassaemia.
SEARCH STRATEGY
We searched the Cochrane Haemoglobinopathies Trials Register, MEDLINE, EMBASE, ZETOC, Current Controlled Trials and bibliographies of relevant publications. We also contacted the manufacturers of desferrioxamine and other iron chelators. Date of last searches: April 2004.
SELECTION CRITERIA
Randomised controlled trials comparing desferrioxamine with placebo; with another iron chelator; or comparing two schedules of desferrioxamine, in people with transfusion-dependent thalassaemia.
DATA COLLECTION AND ANALYSIS
Four authors working independently, were involved in trial quality assessment and data extraction. Missing data were requested from the original investigators.
MAIN RESULTS
Eight trials involving 334 people (range 20 to 144 people) were included. One trial compared desferrioxamine with placebo, five compared desferrioxamine with another iron chelator (deferiprone) and two compared different schedules of desferrioxamine. Overall, few trials measured the same outcomes.Compared to placebo, desferrioxamine significantly reduced iron overload. The number of deaths at 12 years follow up and evidence of reduced end-organ damage was less for desferrioxamine than placebo. When desferrioxamine was compared to deferiprone or a different desferrioxamine schedule there were no statistically significant differences in measures of iron overload. Compliance was recorded by two trials. Compliance was less for desferrioxamine than deferiprone in one trial and of no difference in comparison with desferrioxamine and deferiprone combined with a second trial. Adverse events were recorded in trials comparing desferrioxamine with other iron chelators. There was evidence of adverse events in all treatment groups. In one trial, adverse events were significantly less likely with desferrioxamine than deferiprone, relative risk 0.45 (95% confidence interval 0.24 to 0.84). Assessment of the methodological quality of included trials was not possible, given the general absence of these data in the trials.
AUTHORS' CONCLUSIONS
We found no reason to change current treatment recommendations. However, considerable uncertainty continues to exist about the optimal schedule for desferrioxamine in people with transfusion-dependent thalassaemia.
Topics: Chelation Therapy; Deferiprone; Deferoxamine; Humans; Iron Chelating Agents; Iron Overload; Pyridones; Randomized Controlled Trials as Topic; Thalassemia; Transfusion Reaction
PubMed: 16235363
DOI: 10.1002/14651858.CD004450.pub2