Vigabatrin withdrawal randomized study in children

Chiron, Catherine; Dulac, Olivier; Gram, Lennart

doi:10.1016/s0920-1211(96)00028-9

Cited by 36 publications

(13 citation statements)

References 11 publications

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“…The favorable response to STP as an add-on treatment (mainly with CBZ) in refractory partial epilepsy has been reported, with the percentage of responders approaching 75% (5). The rate of responders is slightly lower in our study where most patients were receiving VGB, a recently approved drug, which has demonstrated major efficacy in partial epilepsy in children (26)(27)(28)(29) and infants (30). Although used as a third-line therapy, STP showed one of the highest rates of efficacy for a new AED in an open study dedicated to partial seizures in pediatrics (30)(31)(32).…”

Section: Efficacy Of Stp In Childrenmentioning

confidence: 52%

“…Although half the patients in the present series entered a placebo phase, in the absence of a double-blind step, the trial must be considered as an open study. Such a noncontrolled study, however, conducted on a large series of patients allowed us to determine the best possible applications of the drug and therefore to select study subjects with particular syndromes for further controlled trials, a strategy particularly useful in childhood epilepsy (25,26).…”

Section: Methodologic Issuesmentioning

confidence: 99%

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Stiripentol: Efficacy and Tolerability in Children with Epilepsy

et al. 1999

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Summary:Purpose: Stiripentol (STP) is a new antiepileptic drug (AED) that inhibits cytochrome P,,,, resulting in increased plasma concentrations of concomitant AEDs. The efficacy and tolerability of STP as an add-on therapy in children were assessed.Methods: Two hundred twelve patients with refractory epilepsy, aged from 1 month to 20.5 years, received STP either in a single-blind, placebo-controlled trial (I08 patients) or in a further open trial (104 other patients selected by epilepsy syndrome for possible efficacy based on the results of the previous trial).Results: Among the 97 patients who could be analyzed for efficacy in the placebo-controlled study, the median seizure frequency was lower at 3 months with STP than with the placebo (p < 0.0001); 49% responded to the drug, including 10% who became seizure free. Patients with partial epilepsy had the highest response rate (57%). Results were confirmed in the open study where 68% of the 91 patients receiving STP responded at 3 months. These patients were mainly those with partial epilepsy (73%) who were receiving carbamazepine (CBZ) (75%) as comedication (p < 0.001). Ten of the 20 children with severe myoclonic epilepsy in infancy also responded with clobazam (CLB) as comedication. Efficacy was sustained long term in 74% of the 94 patients still receiving STP at a mean 30-month follow-up. Adverse events were reported in 48% of the 212 patients, mainly anorexia and loss of weight, but these events required STP discontinuation in only nine cases. Side effects were minimized in the open trial by optimizing the dose of comedication.Conclusions: STP seems to be a promising add-on drug, particularly when combined with CBZ in patients with partial childhood epilepsy refractory to vigabatrin (VGB) and with CLB in patients with severe myoclonic epilepsy in infancy.

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Section: Efficacy Of Stp In Childrenmentioning

confidence: 52%

Section: Methodologic Issuesmentioning

confidence: 99%

Stiripentol: Efficacy and Tolerability in Children with Epilepsy

et al. 1999

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“…Clinical researchers in pediatric epilepsy have already initiated this process: examples can be found in which focused trials involve small but homogeneous populations (Chiron et al, 2000); enrichment trials in which only responders in the first open phase are randomized to either maintain treatment or switch to placebo (Chiron et al, 1996;Pina-Garza et al, 2007); meta-analysis gathering several trials, each one involving small populations (Kassai et al, 2008); sequential analyses in order to include the minimum number of patients necessary to demonstrate an effect; mathematical modeling applied to DEVELOPING ANTIEPILEPTIC DRUGS IN CHILDREN: BALANCING PROTECTION AND ACCESS 743 pharmacokinetics for example in order to extrapolate the optimal dose from adults to children without repeating the study in children; or analysis of epidemiological observational data representing "real life" in lieu of useless trials to know better the effect of the compound in real practice.…”

Section: Using Innovative Strategiesmentioning

confidence: 99%

Developing antiepileptic drugs in children

Amann

Glauser

Chiron

2013

Handbook of Clinical Neurology

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“…One assumption is that "the treatment will not cure the condition during the open-label stage" (Amery and Dony 1975). For this reason, RDT is generally applied under conditions that require sustained use of a treatment, such as in treating chronic diseases and stabilizing tumor growth (Chiron et al 1996). Another assumption is that the treatment effect(s) of the open-label stage will not be carried over to the second stage.…”

Section: Introductionmentioning

confidence: 99%

Randomized Discontinuation Trials With Binary Outcomes

Fedorov

Liu

2013

Journal of Statistical Theory and Practice

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Randomized discontinuation trial (RDT) has gained popularity across a number of therapeutic areas. Oncology is one of the most known. In the simplest case, at the initial open-label stage all patients are treated with the experimental treatment to identify a population of responders. This stage is followed by a randomized two-arm trial to compare two conditions, for example, treatment versus placebo. Potentially RDT increases the efficiency of trials relatively to traditional designs gaining information from a sensitized population if the open-label stage provides a reliable separation of responders from nonresponders. Often a sensitized population is called an enriched population, and respectively, the RDT is called "enrichment experiment." We compare RDT with the traditional two-arm randomized clinical trials (RCT) for binary outcomes assuming that the population of interest consists of three groups: placebo responders, treatment-only responders, and nonresponders. Our results are derived in the "parameter estimation" setting and they are based on the comparison of estimator variances. We identify conditions under which RDT is either superior or inferior to RCT in terms of response rates, misclassification rates, and clinical ethics. Extension of our results to design optimization, hypothesis testing, and sample size calculation is rather straightforward.

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Vigabatrin withdrawal randomized study in children

Cited by 36 publications

References 11 publications

Stiripentol: Efficacy and Tolerability in Children with Epilepsy

Stiripentol: Efficacy and Tolerability in Children with Epilepsy

Developing antiepileptic drugs in children

Randomized Discontinuation Trials With Binary Outcomes

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