Intravenous Methylprednisolone Versus Oral Prednisolone for Infantile Spasms (MPIV)

Intravenous Methylprednisolone Versus High Dose Oral Prednisolone for the Treatment of Infantile Spasms: a Randomized Open-labelled Trial

Infantile Spasms (IS) are classically refractory to the usual antiepileptic drugs and often pose a therapeutic challenge. Since, there is associated significant morbidity, much effort has been directed over the past years to evaluate the role of various anticonvulsants in the management of IS. High dose oral prednisolone has been shown to cause early cessation of spasms and resolution of hypsarrythmia on Electroencephalogram. Recently, role of intravenous methylprednislone pulse therapy has been explored as one of the therapeutic modality in IS, in order to avoid the development of side-effects associated with prolonged oral steroid therapy and maintain long-term efficacy.However, there are no studies comparing iv methylprednisolone pulse therapy with high dose oral prednisolone..

Study Overview

• Status: Unknown
• Conditions: Infantile Spasm
• Intervention / Treatment: Drug: Intravenous Methylprednisolone; Drug: Oral Pednisolone

Detailed Description

Multiple studies have subsequently used higher dose of prednisolone in infantile spasms at the weight based dosing of 4-8 mg/kg/day with a maximum dose of 60mg/day. The results have shown high rates of clinical and elecroencephalographic remission with lower relapse rates.However, a major concern related to corticosteroids, especially in infants and children, is the possible development of side effects. The most frequent ones are excessive weight gain, hyperphagia, water retention with edema, cushingoid appearance, hypertension, behavioral disturbances, increased infection susceptibility, leukopenia, electrolyte disturbances, hyperglycemia, glycosuria, impaired glucose tolerance, frank diabetes and sleep disorders. Furthermore, long-term side effects such as hypothalamus-pituitary axis suppression, psychosis, osteoporosis, nephrocalcinosis, brain atrophy, cataracts and, in children, growth retardation, have also been reported.

Recently, role of intravenous methylprednislone pulse therapy has been explored as one of the therapeutic modality in IS, in order to avoid the development of side-effects associated with prolonged oral steroid therapy and maintain long-term efficacy. There have been few studies on use of iv pulse methylprednisolone in IS with small sample size, showing to a rapid improvement in EEG & cessation of spasm in majority of the infants without significant adverse effects.

Emerging evidence suggests that intravenous pulse methylprednisolone might have superior efficacy and better safety profile when compared to high dose oral prednisolone in treatment of IS.

Hence, present study aims at comparing intravenous pulse methylprednisolone versus oral prednisolone in an open label, RCT for treatment of children with IS.

• Study Type: Interventional
• Enrollment (Anticipated): 128
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Dipti Kapoor, MD; Phone Number: 91-9818426830; Email: diptikumar81@yahoo.co.in
• Study Contact Backup: Name: Suvasini Sharma, MD, DM; Phone Number: 91-9910234344; Email: sharma.suvasini@gmail.com

Study Locations

• India
  • Delhi
    • New Delhi, Delhi, India, 110001
      • Recruiting
      • Lady Hardinge Medical College
      • Principal Investigator: Dipti Kapoor, MD
      • Sub-Investigator: Suvasini Sharma, MD,DM
      • Sub-Investigator: Sharmila B Mukherjee, MD
      • Sub-Investigator: Bijoy Patra, MD
      • Sub-Investigator: Harish Pemde, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 11 months to 1 year (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Newly diagnosed patients aged 4 - 30 months with epileptic spasms in clusters with electroencephalographic evidence of hypsarrhythmia or its variants with or without developmental delay -

Exclusion Criteria:

1. Children with recognized progressive neurological illness will be excluded.
2. Children with chronic renal, pulmonary, cardiac or hepatic dysfunction

3. Severe malnutrition (weight for length and height for less than 3 SD for mean as per WHO growth charts)

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Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention arm; Pulse intravenous methylprednisolone (30 mg / kg for 3 days) followed by 1-week taper of oral prednisolone Day 1-3 Intravenous Methylprednisolone in dose of 30 mg/kg/day Day 4-6 Oral Prednisolone in dose of 2mg/kg/day Day 7-10 Oral Prednisolone in dose of 1mg/kg/day	Drug: Intravenous Methylprednisolone; Intravenous Methylprednisolone will be used in the intervention group
Active Comparator: Control; Oral prednisolone (4 mg/kg/day) for 2 weeks followed by tapering over 2 weeks Day 1-14 (2 weeks): dose 4mg/kg/day Day 15-21 (1 weeks): 2mg/kg/day Day 22-28 (1 weeks): 1mg/kg/day	Drug: Oral Pednisolone; Oral Prednisolone will be used in the Control Group

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of children who achieved spasm freedom as per parental reports in both the groups	The proportion of children who achieve spasm freedom defined as no witnessed spasms on and between day 14 and day 42 as per parental reports will be evaluated in the both the groups	6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of days after initiation of trial treatment on which spasms were not seen and after which response was maintained until 6 weeks (day 42) of treatment in both the groups	Number of days after initiation of trial treatment on which spasms were not seen and after which response was maintained until 6 weeks (day 42) of treatment in both the groups	6 weeks
Proportion of children who achieve resolution of hypsarrhythmia on electro encephalogram at 2 weeks (in all cases) and at 6 weeks (for cases with sustained clinical response) in both the groups.	Proportion of children who achieve resolution of hypsarrhythmia on electro encephalogram at 2 weeks (in all cases) and at 6 weeks (for cases with sustained clinical response) in both the groups.	6 weeks
Description and proportion of the adverse effects of methylprednisolone in the experimental group	Description and proportion of the adverse effects of methylprednisolone in the experimental group	6 weeks

Collaborators and Investigators

• Sponsor: Suvasini Sharma
• Investigators: Principal Investigator: Dipti Kapoor, MD, Lady Hardinge Medical College

Publications and helpful links

General Publications

• Kapoor D, Sharma S, Garg D, Samaddar S, Panda I, Patra B, Mukherjee SB, Pemde HK. Intravenous Methylprednisolone Versus Oral Prednisolone for West Syndrome: A Randomized Open-Label Trial. Indian J Pediatr. 2021 Aug;88(8):778-784. doi: 10.1007/s12098-020-03630-3. Epub 2021 Feb 11.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2019
• Primary Completion (Anticipated): April 30, 2022
• Study Completion (Anticipated): October 31, 2022

Study Registration Dates

• First Submitted: March 12, 2019
• First Submitted That Met QC Criteria: March 13, 2019
• First Posted (Actual): March 15, 2019

Study Record Updates

• Last Update Posted (Actual): November 18, 2019
• Last Update Submitted That Met QC Criteria: November 14, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Keywords: Prednisolone; Methylprednisolone; Hypsarrythmia
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsy, Generalized; Epileptic Syndromes; Neurologic Manifestations; Neuromuscular Manifestations; Epilepsy; Spasms, Infantile; Spasm; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Neuroprotective Agents; Protective Agents; Prednisolone; Methylprednisolone Acetate; Methylprednisolone; Methylprednisolone Hemisuccinate; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate
• Other Study ID Numbers: MethylpredIV

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No