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To report a prospectively planned analysis of two randomised controlled trials with embedded comparisons of prednisolone versus tetracosactide depot for the treatment of infantile epileptic spasms syndrome (IESS). Individual patient data from patients randomly allocated to prednisolone or tetracosactide depot were analysed from two trials (UKISS, ICISS). The comparison was embedded within trials in which some patients also received vigabatrin but only patients receiving monotherapy with randomly allocated hormonal treatments are included in this analysis. The main outcome was cessation of spasms (Days 13–14 after randomisation). Lead time to treatment and underlying aetiology were taken into account. Cessation of spasms on Days 14–42 inclusive, electroclinical response (EEG Day 14), plus developmental and epilepsy outcomes (at 14 months in UKISS and 18 months in ICISS) are also reported. Minimum treatment was prednisolone 40 mg per day for two weeks or tetracosactide depot 0·5 mg IM on alternate days for two weeks, all followed by a reducing dose of prednisolone over two weeks. 126 infants were included in this study. On tetracosactide depot, 47 of 62 (76%) were free of spasms on Days 13–14 compared to 43 of 64 (67%) on prednisolone (difference 9%, 95% CI -7·2% to +25·2%, chi square 1·15, p = 0·28). For Day 14–42 cessation of spasms, on tetracosactide depot, 41 of 61 (67%) were free of spasms compared to 35 of 62 (56%) on prednisolone (difference 11%, 95% CI -6·4% to +28·4%, chi square 1·51, p = 0·22). There was no significant difference in mean VABS score between infants who received prednisolone compared with those who received tetracosactide depot (74·8 (SD 18·3) versus 78·0 (SD 20·2) t = −0·91 p = 0·36). The proportion with ongoing epilepsy at the time of developmental assessment was 20 of 61 (33%) in the tetracosactide group compared with 26 out of 63 (41%) in the prednisolone group (difference 8%, 95% CI -9·2% to +25·2%, Chi [2] 0·95, p = 0·33). With hormone monotherapy, either prednisolone or tetracosactide depot may be recommended for infantile epileptic spasms syndrome. • Embedding a second randomisation in trials effectively provides additional information about trial treatments. • There was no significant difference between prednisolone and tetracosactide depot in those achieving early spasm cessation. • There was no significant difference between trial treatments in those free of epileptic seizures at 14 and 18 months. • Developmental outcome was similar in both treatment groups. • Either prednisolone or tetracosactide depot can be recommended when using hormonal treatment as monotherapy. [ABSTRACT FROM AUTHOR]

Background Infantile spasms, which comprise a severe infantile seizure disorder, have a high morbidity and are difficult to treat. Hormonal treatments (adrenocorticotropic hormone and prednisolone) have been the main therapy for decades, although little evidence supports their use. Vigabatrin has been recorded to have a beneficial effect in this disorder. We aimed to compare the effects of vigabatrin with those of prednisolone and tetracosactide in the treatment of infantile spasms.Methods The United Kingdom Infantile Spasms Study assessed these treatments in a multicentre, randomised controlled trial in 150 hospitals in the UK. The primary outcome was cessation of spasms on days 13 and 14. Minimum doses were vigabatrin 100 mg/kg per day, oral prednisolone 40 mg per day, or intramuscular tetracosactide depot 0·5 mg (40 IU) on alternate days. Analysis was by intention to treat.Findings Of 208 infants screened and assessed, 107 were randomly assigned to vigabatrin (n=52) or hormonal treatments (prednisolone n=30, tetracosactide n=25). None was lost to follow-up. Proportions with no spasms on days 13 and 14 were: 40 (73%) of 55 infants assigned hormonal treatments (prednisolone 21/30 [70%], tetracosactide 19/25 [76%]) and 28 (54%) of 52 infants assigned vigabatrin (difference 19%, 95% CI 1%–36%, p=0·043). Two infants allocated tetracosactide and one allocated vigabatrin received prednisolone. Adverse events were reported in 30 (55%) of 55 infants on hormonal treatments and 28 (54%) of 52 infants on vigabatrin. No deaths were recorded.Interpretation Cessation of spasms was more likely in infants given hormonal treatments than those given vigabatrin. Adverse events were common with both treatments. [Copyright &y& Elsevier]