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

Study Status: Not yet recruiting
Recruit Status: Not yet recruiting
Study Type: Interventional

Official Title: Prednisolone vs. Vigabatrin in the First-line Treatment of Infantile Spasms

Brief 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.

Detailed Summary:

Background and Rationale for the study:

Infantile spasms (IS) is a rare, catastrophic age-specific epilepsy syndrome with onset within the first 12 months of life. The disorder is characterized clinically by epileptic spasms, often accompanied by developmental regression and a characteristic interictal electroencephalography (EEG) pattern called hypsarrhythmia. When all these three features are present, the term, "West syndrome" is commonly used. The catastrophic nature of the disorder is due to the frequent sequelae of severe global neurodevelopmental delay and medically refractory epilepsy.

The initial age of onset in 90% of cases occur before 12 months of life, with peak onset at 6 months. The incidence is 2 to 3 per 10,000 live births with a lifetime prevalence of 1.5 to 2 per 10,000 children. It is slightly more common in males, and a family history exists in 3%-6% of cases.1,2,3 The etiology of IS has conventionally been divided into symptomatic or cryptogenic, depending on whether the underlying cause is known. Conditions causing symptomatic IS are diverse and can include focal or multifocal brain injuries, chromosomal abnormalities and genetic mutations and inborn errors of metabolism. In about 20% of cases, the identifiable cause remains unknown and these are defined as cryptogenic.

The spontaneous remission rate of IS in limited natural history studies is 30%.4,5 Although the clinical spasms and typical EEG pattern disappear by 3 to 4 years of age, up to 60% of children with IS will go on to develop other types of refractory seizures, including Lennox Gastaut syndrome. The poor developmental outcome in IS is primarily due to the underlying etiology, however, delay in diagnosis and treatment6 and the use of ineffective therapies are also contributory fact
Sponsor: The Hospital for Sick Children

Current Primary Outcome: Resolution of Infantile spasms and Hypsarrhythmia [ Time Frame: 14 days ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

• Clinical or EEG relapse of Infantile Spasms [ Time Frame: 6 months ]

  Clinical relapse: any spasm occurring after 2 weeks up to and including final clinical assessment at approximately 5 months (+/- 2weeks) post-treatment in an infant who had cessation of spasms.

  EEG Relapse: recurrence of hypsarrhythmia/modified hypsarrhythmia pattern after one previous EEG showing resolution of hypsarrhythmia

• Seizure outcome at final follow up (presence or absence of any seizure types at final follow up as assessed by seizure diary and on history at final follow up visit) [ Time Frame: 6 months ]
  Clinical assessment of the presence or absence of any seizure types at final follow up as assessed by seizure diary and on history at final follow up visit.
• Time to cessation of Infantile spasms [ Time Frame: 14 days ]
  Length of time in days to achieve cessation of Infantile spasms
• Time to relapse [ Time Frame: 6 months ]
  Length of time (in days) from the initial resolution of Infantile spasms to the relapse of Infantile spasms

Original Secondary Outcome: Same as current

Information By: The Hospital for Sick Children

Dates:
Date Received: November 18, 2014
Date Started: September 2016
Date Completion: March 2020
Last Updated: April 16, 2016
Last Verified: April 2016