Authors :
Presenting Author: Parth Lal, MBBS, MD – Post Graduate Institute of Medical Education and Research
Sandeep Negi, PhD – Post Graduate Institute of Medical Education and Research
Kiran Prakash, MD – Government Medical College and Hospital , Sector 32 , Chandigarh
Dipika Bansal, PhD – National Institute of Pharmaceutical Education and Research
Naveen Sankhyan, MD,DM – Post Graduate Institute of Medical Education and Research
Jitendra Sahu, MD,DM – Post Graduate Institute of Medical Education and Research
Rationale:
Globally, there are differences in management practices among pediatric neurologists in choosing antiseizure medicine in children with infantile epileptic spasms syndrome (IESS) after failing to hormonal and vigabatrin therapy. Our trial aimed to determine whether oral nitrazepam has superior effectiveness than oral topiramate therapy in achieving complete cessation of epileptic spasms for children with IESS who were resistant to hormonal and vigabatrin treatment.
Methods:
This was an open-label, randomized controlled clinical trial with a superiority hypothesis and masked end-point assessments. The primary effectiveness endpoint was a complete and sustained cessation of epileptic spasms (ES) for four weeks, assessed at 10 weeks since randomization. The secondary endpoints were proportion of children with electroclinical remission, time to remission, quality of life assessed by Hi-QUALIN (Hindi version of Quality Of life of the Infant), autonomic tone assessed by heart rate variability and adverse events. Results:
Between June 2023 and December 2024, a total of 80 children with resistant IESS were screened. Of these, 40 eligible children (29 boys, 11 girls) were randomized to receive either oral nitrazepam at 0.5-3 mg/kg/day (n=20) or topiramate at 2-12 mg/kg/day (n = 20). Comparison of effectiveness measures between nitrazepam and topiramate were: complete cessation of epileptic spasms (ES) (55% vs. 15%, p = 0.019) and electroclinical remission (45% vs. 10%, p = 0.031), quality of life scores (p = 0.023). The parasympathetic heart rate variability parameters were significantly higher amongst responders with nitrazepam as compared with responders with topiramate. Sedation was frequent with nitrazepam while irritability was with topiramate.Conclusions:
Our trial provides proof-of-concept of the superior short-term effectiveness of nitrazepam over topiramate therapy in resistant IESS. It also demonstrated better quality of life improvements and autonomic stability. Further studies are needed to evaluate its long-term efficacy and safety.
Clinical Trials Registry of India (CTRI/2023/06/053933)
Funding: Institutional Thesis Grant and Indian Journal of Pediatrics.