Prednisolone Versus Vigabatrin in the First-line Treatment of Infantile Spasms

• Status: Withdrawn
• Trial end date: 2019-03-06
• Target enrollment: 0
• Participant gender: All

Summary

Infantile Spasms, is an rare age-specific epilepsy of early infancy. A 2012 American Academy Neurology/ Child Neurology Society practice parameter update on the medical treatment of infantile spasms concluded: adrenocorticotrophic hormone or vigabatrin may be offered for short-term treatment of infantile spasms. There was insufficient evidence to recommend the use of prednisolone, dexamethasone, and methylprednisolone. The cost of ACTH and the side effects of vigabatrin have led to the consideration of alternative medications to treat infantile spasms. The United Kingdom Infantile Spasms Study (UKISS) in 2004, comparing the efficacy of intramuscular synthetic ACTH to high dose oral prednisolone, showed a response rate of 74% for ACTH and 70% for prednisolone. Since the UKISS paper was published, many institutions in the United States and Australia have used oral prednisolone instead of ACTH, partly due to the exorbitant cost of intramuscular ACTH but also its ease of use and better adverse event profile compared to ACTH. Prednisolone and vigabatrin are both oral medications, which can be initiated promptly upon diagnosis of infantile spasms, expediting treatment and shortening treatment lag time. Because the UKISS trial is the only Class 3 study providing evidence for oral prednisolone in the first-line treatment of infantile spasms, further prospective studies are needed.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: The Hospital for Sick Children
• Treatments: Methylprednisolone; Methylprednisolone Acetate; Methylprednisolone Hemisuccinate; Prednisolone; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate; Vigabatrin

Criteria

Inclusion Criteria: Inclusion criteria:

1. Age 2-24 months

2. Clinical spasms

3. Initial EEG with hypsarrhythmia or modified hypsarrhythmia

The inclusion criteria do not quantify the initial severity or frequency of infantile spasms. Infantile spasms is a unique epileptic disorder characterized by clusters of brief infantile spasms, where each one lasts a few seconds and cluster may last minutes. The diagnosis of infantile spasms and response to medication depends on the presence or absence of these events and the frequency of infantile spasms has not been used to determine medication efficacy in previous studies. A seizure diary will be used to quantify the seizure burden, however efficacy will depend on complete resolution of clinical spasms and resolution of hypsarrhythmia on EEG -

Exclusion Criteria:

1. Age <2months or older than 24 months

2. Tuberous sclerosis (if known at the time of enrolment)

3. Previous treatment (within 28 days) with VGB or hormonal treatments

4. Contraindications to hormonal therapy: This includes untreated systemic fungal infections, known hypersensitivity to prednisolone or other corticosteroids, or to any of the non-medicinal ingredients present in the solution. Active or latent tuberculosis, ocular herpes simplex, hypothyroidism, hepatic cirrhosis, nonspecific ulcerative colitis, abscess or other pyogenic infection, fresh intestinal anastomoses, active or latent peptic ulcer, renal insufficiency, hypertension, osteoporosis, cardiac disease, thromboembolic disorders and diabetes mellitus. All patients with cardiac risk factors will receive an electrocardiogram (ECG), chest xray (CXR) and cardiology referral if indicated. Patients diagnosed with cardiac disorders will be excluded from the study since high dose steroids may exacerbate arrhythmias.

5. Inability of parents or guardians to give consent

6. Enrolment in a concurrent treatment trial that might affect outcome measures of this trial -