Early survival of comatose patients after severe traumatic brain injury with the dual cannabinoid CB1/CB2 receptor agonist KN38-7271: A randomized, double-blind, placebo-controlled phase II trial

Journal of Neurological Surgery, Part A: Central European Neurosurgery

Volumn 73, Issue 4, 2012, Pages 204-216

  Firsching, Raimund ^a   Piek, Jürgen ^b   Skalej, Martin ^c   Rohde, Veit ^d   Schmidt, Uwe ^e   Striggow, Frank ^f,g  

^a UNIVERSITY HOSPITAL MAGDEBURG   (Germany)

^b ROSTOCK UNIVERSITY MEDICAL CENTER   (Germany)

^c OTTO VON GUERICKE UNIVERSITY   (Germany)

^d UNIVERSITY OF GÖTTINGEN   (Germany)

^e StatConsult Gesellschaft für Klinische und Versorgungsforschung MbH   (Germany)

^f KeyNeurotek Pharmaceuticals AG   (Germany)

^g GERMAN CENTER FOR NEURODEGENERATIVE DISEASES DZNE   (Germany)

Author keywords

Cannabinoid receptor agonist; Cannabinoids; Severe head trauma; Traumatic brain injury

Indexed keywords

CANNABINOID 1 RECEPTOR; CANNABINOID 1 RECEPTOR AGONIST; CANNABINOID 2 RECEPTOR; CANNABINOID 2 RECEPTOR AGONIST; KN 387271; PLACEBO; UNCLASSIFIED DRUG; 3 (2 HYDROXYMETHYLINDANYL 4 OXY)PHENYL 4,4,4 TRIFLUORO 1 SULFONATE; 3-(2-HYDROXYMETHYLINDANYL-4-OXY)PHENYL-4,4,4-TRIFLUORO-1-SULFONATE; INDAN DERIVATIVE; SULFONIC ACID DERIVATIVE;

ADULT; ARTICLE; BRAIN PERFUSION; CLINICAL ARTICLE; COMATOSE PATIENT; CONTROLLED STUDY; DOUBLE BLIND PROCEDURE; DRUG EFFICACY; DRUG SAFETY; FEMALE; HUMAN; INTRACRANIAL PRESSURE; MALE; MENTAL DETERIORATION; MIDDLE AGED; NEUROPROTECTION; PHASE 2 CLINICAL TRIAL; PROSPECTIVE STUDY; RANDOMIZED CONTROLLED TRIAL; SURVIVAL; TRAUMATIC BRAIN INJURY; TREATMENT DURATION; YOUNG ADULT; ADOLESCENT; BRAIN INJURY; CLINICAL TRIAL; COMA; COMPUTER ASSISTED TOMOGRAPHY; CONTROLLED CLINICAL TRIAL; DRUG POTENTIATION; GLASGOW COMA SCALE; KAPLAN MEIER METHOD; MORTALITY; NEUROLOGIC EXAMINATION; NUCLEAR MAGNETIC RESONANCE IMAGING; PATHOPHYSIOLOGY; PUPIL REFLEX; STATISTICAL ANALYSIS; TREATMENT OUTCOME;

ADOLESCENT; ADULT; BRAIN INJURIES; COMA; DATA INTERPRETATION, STATISTICAL; DOUBLE-BLIND METHOD; FEMALE; GLASGOW COMA SCALE; HUMANS; INDANS; KAPLAN-MEIER ESTIMATE; MAGNETIC RESONANCE IMAGING; MALE; MIDDLE AGED; NEUROLOGIC EXAMINATION; RECEPTOR, CANNABINOID, CB1; RECEPTOR, CANNABINOID, CB2; REFLEX, PUPILLARY; SULFONIC ACIDS; SURVIVAL; TOMOGRAPHY, X-RAY COMPUTED; TREATMENT OUTCOME; YOUNG ADULT;

EID: 84869885231     PISSN: 21936315     EISSN: 21936323     Source Type: Journal    
DOI: 10.1055/s-0032-1304815     Document Type: Article

References (35)

1. Bruns J. Jr, Hauser W. A. The epidemiology of traumatic brain injury: a review. Epilepsia: 2003; 44 Suppl 10 2 10 (Pubitemid 37280386)
2. Ghajar J. Traumatic brain injury. Lancet: 2000; 356 9233 923 929
3. Maas A. I., Murray G., Henney H. III., et al. Pharmos TBI investigators. Efficacy and safety of dexanabinol in severe traumatic brain injury: results of a phase III randomised, placebo-controlled, clinical trial. Lancet Neurol: 2006; 5 1 38 45 (Pubitemid 41790694)
4. Roberts I., Yates D., Sandercock P., et al. CRASH trial collaborators. Effect of intravenous corticosteroids on death within 14 days in 10008 adults with clinically significant head injury (MRC CRASH trial): randomised placebo-controlled trial. Lancet: 2004; 364 9442 1321 1328
5. Vink R., Nimmo A. J., Cernak I. An overview of new and novel pharmacotherapies for use in traumatic brain injury. Clin Exp Pharmacol Physiol: 2001; 28 11 919 921 (Pubitemid 33071067)
6. Di Marzo V., Bifulco M., De Petrocellis L. The endocannabinoid system and its therapeutic exploitation. Nat Rev Drug Discov: 2004; 3 9 771 784 (Pubitemid 39242829)
7. Katona I., Freund T. F. Endocannabinoid signaling as a synaptic circuit breaker in neurological disease. Nat Med: 2008; 14 9 923 930
8. Piomelli D., Giuffrida A., Calignano A., Rodríguez de Fonseca F. The endocannabinoid system as a target for therapeutic drugs. Trends Pharmacol Sci: 2000; 21 6 218 224 (Pubitemid 30331091)
9. Marsicano G., Goodenough S., Monory K., et al. CB1 cannabinoid receptors and on-demand defense against excitotoxicity. Science: 2003; 302 5642 84 88 (Pubitemid 37210691)
10. Nagayama T., Sinor A. D., Simon R. P., et al. Cannabinoids and neuroprotection in global and focal cerebral ischemia and in neuronal cultures. J Neurosci: 1999; 19 8 2987 2995 (Pubitemid 29173995)
11. Eljaschewitsch E., Witting A., Mawrin C., et al. The endocannabinoid anandamide protects neurons during CNS inflammation by induction of MKP-1 in microglial cells. Neuron: 2006; 49 1 67 79 (Pubitemid 43017186)
12. Wolf S. A., Tauber S., Ullrich O. CNS immune surveillance and neuroinflammation: endocannabinoids keep control. Curr Pharm Des: 2008; 14 23 2266 2278
13. Mauler F., Hinz V., Augstein K. H., Fassbender M., Horváth E. Neuroprotective and brain edema-reducing efficacy of the novel cannabinoid receptor agonist BAY 38-7271. Brain Res: 2003; 989 1 99 111 (Pubitemid 37281406)
14. Mauler F., Horváth E., De Vry J., et al. BAY 38-7271: a novel highly selective and highly potent cannabinoid receptor agonist for the treatment of traumatic brain injury. CNS Drug Rev: 2003; 9 4 343 358 (Pubitemid 38031863)
15. Brihaye J., Frowein R. A., Lindgren S., Loew F., Stroobandt G. Report on the Meeting of the W.F.N.S. Neuro-Traumatology Committee, Brussels, 19-23 September 1976. Acta Neurochir (Wien): 1978; 40 181 186
16. Frowein R. A. Classification of coma. Acta Neurochir (Wien): 1976; 34 1-4 5 10
17. Firsching R., Woischneck D., Klein S., Reissberg S., Döhring W., Peters B. Classification of severe head injury based on magnetic resonance imaging. Acta Neurochir (Wien): 2001; 143 3 263 271 (Pubitemid 32268601)
18. Firsching R., Woischneck D., Klein S., Ludwig K., Döhring W. Brain stem lesions after head injury. Neurol Res: 2002; 24 2 145 146 (Pubitemid 34169258)
19. Firsching R., Roehl F. W., Woischneck D. H., John N., Skalej M. The predictive value of ICP as compared to magnetic resonance imaging in comatose patients after head injury. Acta Neurochir Suppl (Wien): 2008; 102 237 240
20. von Wild K. R., Wenzlaff P. Quality management in traumatic brain injury (TBI): Lessons from the prospective study in 6800 patients after acute TBI in respect of neurorehabilitation. Acta Neurochir Suppl (Wien): 2005; 93 15 25
21. Deutsche Gesellschaft für Neurochirurgie: Leitlinie: Schädel-Hirn-Trauma im Erwachsenenalter 2007. Available at: www.awmf.org/leitlinien/detail/ll/008-001.html
22. Bedell E. A., Prough D. S. Dexanabinol as a treatment for traumatic brain injury: will another therapeutic promise be broken? Crit Care Med: 2002; 30 3 710 711 (Pubitemid 34214647)
23. Belayev L., Busto R., Zhao W., Ginsberg M. D. HU-211, a novel noncompetitive N-methyl-D-aspartate antagonist, improves neurological deficit and reduces infarct volume after reversible focal cerebral ischemia in the rat. Stroke: 1995; 26 12 2313 2319, discussion 2319-2320
24. Brewster M. E., Pop E., Foltz R. L., et al. Clinical pharmacokinetics of escalating i.v. doses of dexanabinol (HU-211), a neuroprotectant agent, in normal volunteers. Int J Clin Pharmacol Ther: 1997; 35 9 361 365 (Pubitemid 27417674)
25. Feigenbaum J. J., Bergmann F., Richmond S. A., et al. Nonpsychotropic cannabinoid acts as a functional N-methyl-D-aspartate receptor blocker. Proc Natl Acad Sci U S A: 1989; 86 23 9584 9587 (Pubitemid 20010472)
26. Knoller N., Levi L., Shoshan I., et al. Dexanabinol (HU-211) in the treatment of severe closed head injury: a randomized, placebo-controlled, phase II clinical trial. Crit Care Med: 2002; 30 3 548 554 (Pubitemid 34214615)
27. Mechoulam R., Feigenbaum J. J., Lander N., et al. Enantiomeric cannabinoids: stereospecificity of psychotropic activity. Experientia: 1988; 44 9 762 764
28. Miller J. D. Prediction of outcome after head injury. A critical review. In: Vigouroux R. P., McLaurin R. L. eds. Advances in Neurotraumatology, Extracerebral collections. Vol. 1. Heidelberg, New York Springer-Verlag: 1986; 230 247
29. Moskopp D., Stähle C., Wassmann H. Problems of the Glasgow Coma Scale with early intubated patients. Neurosurg Rev: 1995; 18 4 253 257 (Pubitemid 26064950)
30. Balestreri M., Czosnyka M., Chatfield D. A., et al. Predictive value of Glasgow Coma Scale after brain trauma: change in trend over the past ten years. J Neurol Neurosurg Psychiatry: 2004; 75 1 161 162 (Pubitemid 38091292)
31. Marshall L. F., Marshall S. B., Klauber M. R., van Berkum M., Clark R. N. A new classification of head injury based on computerized tomography. J Neurosurg: 1991; 75 S14 S20
32. Firsching R., Woischneck D., Diedrich M., et al. Early magnetic resonance imaging of brainstem lesions after severe head injury. J Neurosurg: 1998; 89 5 707 712 (Pubitemid 28485527)
33. Keenan H. T., Nocera M., Bratton S. L. Frequency of intracranial pressure monitoring in infants and young toddlers with traumatic brain injury. Pediatr Crit Care Med: 2005; 6 5 537 541
34. Thompson H. J., Rivara F. P., Jurkovich G. J., Wang J., Nathens A. B., MacKenzie E. J. Evaluation of the effect of intensity of care on mortality after traumatic brain injury. Crit Care Med: 2008; 36 1 282 290
35. Shafi S., Diaz-Arrastia R., Madden C., Gentilello L. Intracranial pressure monitoring in brain-injured patients is associated with worsening of survival. J Trauma: 2008; 64 2 335 340 (Pubitemid 351640438)