Failure of the competitive N-methyl-D-aspartate antagonist Selfotel (CGS 19755) in the treatment of severe head injury: Results of two phase III clinical trials

Gabrielle F. Morris, Ross Bullock, Sharon Bowers Marshall, Anthony Marmarou, Andrew Maas, Lawrence F. Marshall

Research output: Contribution to journalArticle

191 Citations (Scopus)

Abstract

Object. Excessive activity of excitatory amino acids released after head trauma has been demonstrated to contribute to progressive injury in animal models and human studies. Several pharmacological agents that act as antagonists to the glutamate receptor have shown promise in limiting this progression. The efficacy of the N-methyl-D-aspartate receptor antagonist Selfotel (CGS 19755) was evaluated in two parallel studies of severely head injured patients, defined as patients with postresuscitation Glasgow Coma Scale scores of 4 to 8. Methods. A total of 693 patients were prospectively enrolled in two multicenter double-blind studies. Comparison between the treatment groups showed no significant difference with regard to demographic data, previous incidence of hypotension, and severity of injury. As the study progressed, the Safety and Monitoring Committee became concerned about possible increased deaths and serious brain-related adverse events in the treatment arm of the two head injury trials, as well as deaths in the two stroke trials being monitored concurrently. The Selfotel trials were stopped prematurely because of this concern and because an interim efficacy analysis indicated that the likelihood of demonstrating success with the agent if the studies had been completed was almost nil. Conclusions. Subsequently, more complete data analysis revealed no statistically significant difference in mortality rates in all cases between the two treatment groups in the head injury trials. In this report the authors examine the studies in detail and discuss the potential application of the data to future trial designs.

Original languageEnglish
Pages (from-to)737-743
Number of pages7
JournalJournal of Neurosurgery
Volume91
Issue number5
StatePublished - Nov 1 1999
Externally publishedYes

Fingerprint

selfotel
Phase III Clinical Trials
N-Methylaspartate
Craniocerebral Trauma
Excitatory Amino Acid Antagonists
Glasgow Coma Scale
Excitatory Amino Acids
Brain Death
Wounds and Injuries
N-Methyl-D-Aspartate Receptors
Double-Blind Method
Hypotension
Arm
Therapeutics
Animal Models
Stroke
Head
Demography
Pharmacology
Safety

Keywords

  • Clinical trial design
  • Excitatory amino acid
  • Glutamate receptor antagonist
  • N-methyl-D- aspartate
  • Selfotel
  • Severe head injury

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)

Cite this

Failure of the competitive N-methyl-D-aspartate antagonist Selfotel (CGS 19755) in the treatment of severe head injury : Results of two phase III clinical trials. / Morris, Gabrielle F.; Bullock, Ross; Marshall, Sharon Bowers; Marmarou, Anthony; Maas, Andrew; Marshall, Lawrence F.

In: Journal of Neurosurgery, Vol. 91, No. 5, 01.11.1999, p. 737-743.

Research output: Contribution to journalArticle

Morris, Gabrielle F. ; Bullock, Ross ; Marshall, Sharon Bowers ; Marmarou, Anthony ; Maas, Andrew ; Marshall, Lawrence F. / Failure of the competitive N-methyl-D-aspartate antagonist Selfotel (CGS 19755) in the treatment of severe head injury : Results of two phase III clinical trials. In: Journal of Neurosurgery. 1999 ; Vol. 91, No. 5. pp. 737-743.
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