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Spinal Cord Injury: Progress, Promise, and Priorities (2005)

Chapter: Appendix E Clinical Trials of Methylprednisolone

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Suggested Citation:"Appendix E Clinical Trials of Methylprednisolone." Institute of Medicine. 2005. Spinal Cord Injury: Progress, Promise, and Priorities. Washington, DC: The National Academies Press. doi: 10.17226/11253.
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E
CLINICAL TRIALS OF METHYLPREDNISOLONE

The following table summarizes the findings of the American Association of Neurological Surgeons and the Congress of Neurological Surgeons (AANS/CNS, 2002) on studies of methylprednisolone treatment after acute cervical spinal cord injuries.

Suggested Citation:"Appendix E Clinical Trials of Methylprednisolone." Institute of Medicine. 2005. Spinal Cord Injury: Progress, Promise, and Priorities. Washington, DC: The National Academies Press. doi: 10.17226/11253.
×

Description of Study

Evidence Class (Comments)

Results

Reference

Multicenter, double-blind randomized trial comparing different MP doses (1,000 versus 100 mg/d for 11 d) for treatment of 330 ASCI patients (NASCIS I study)

III (study design, data presentation, interpretation, and analysis flaws)

No treatment effect at 6 wk and 6 mo postinjury, no control group

Bracken et al. (1984)

1-yr follow-up of NASCIS I study

III (study design, data presentation, interpretation, and analysis flaws)

No significant difference in neurological recovery of motor or sensory function at 1 yr postinjury

Bracken et al. (1985)

Multicenter, randomized, double-blind, placebo-controlled trial comparing MP treatment with naloxone and placebo treatment in 487 patients (NASCIS II study)

III (study design, data presentation, interpretation, and analysis flaws)

Significant improvement in motor change scores (P = 0.03) and sensation change scores (P = 0.02) at 6 mo postinjury for patients treated with MP within 8 h of injury

Bracken et al. (1990)

1-yr follow-up of NASCIS II study

III (study design, data presentation, interpretation, and analysis flaws)

Significant improvement in motor change scores 1 yr postinjury for patients treated with MP within 8 h of injury (P = 0.03); administration of MP was detrimental if it was given more than 8 h after injury

Bracken et al. (1992)

Suggested Citation:"Appendix E Clinical Trials of Methylprednisolone." Institute of Medicine. 2005. Spinal Cord Injury: Progress, Promise, and Priorities. Washington, DC: The National Academies Press. doi: 10.17226/11253.
×

Description of Study

Evidence Class (Comments)

Results

Reference

Prospective assessment of 15 patients from 1990 to 1993 with retrospective review of 17 patients from 1987 to 1990 to assess differences in treatment outcomes with MP treatment compared with those with treatment without corticosteroids

III

No difference in neurological outcomes between the two sets of patients; patients treated with MP had immune response alterations, higher rates of pneumonia, and longer hospital stays than patients who did not receive corticosteroids

Galandiuk et al. (1993)

Concurrent cohort comparison study (population based) of 363 ASCI patients managed from 1990 to 1991 and 1993; 188 patients received the NASCIS II MP regimen, whereas 90 patients did not receive MP

III (inadequate statistical power)

No differences in neurological outcomes between MP-treated and non-MP-treated patients by use of the Frankel classification; however, insufficient numbers of patients may have been included to show significant differences

Gerhart et al. (1995)

Retrospective review of 145 ASCI patients: 80 treated with MP and 65 not treated

III

No difference in mortality or neurological outcome between groups, despite the younger age and less severe injuries in MP-treated patients

George et al. (1995)

Suggested Citation:"Appendix E Clinical Trials of Methylprednisolone." Institute of Medicine. 2005. Spinal Cord Injury: Progress, Promise, and Priorities. Washington, DC: The National Academies Press. doi: 10.17226/11253.
×

Retrospective review with historical control of 231 ASCI patients; 91 were excluded; comparison of medical complications among 93 MP-treated patients with those among 47 who received no corticosteroid

III

MP-treated patients had significant increases in pneumonia (P = 0.02), acute pneumonia (P = 0.03), number of days with ventilation (P = 0.04), and lengths of ICU stay (P = 0.45); but MP had no adverse effect on long-term outcome

Gerndt et al. (1997)

Case-control analysis of 71 consecutive ASCI admissions; 63 were available for 13 to 57 mo of follow-up; 38 patients were treated with MP, and 25 patients referred >8 h after injury received no MP

III

Multiple factors influenced recovery after SCI; neither MP nor surgery had an effect on the outcome

Poynton et al. (1997)

Multicenter, randomized, double-blind trial comparing MP administered for 24 h with MP administered for 48 h and TM for treatment of 499 ASCI patients (NASCIS III study)

III (study design, data presentation, interpretation, and analysis flaws)

Patients administered MP for 48 h had improved motor recovery at 6 wk and at 6 mo compared with those treated with MP for 24 h and TM for 48 h (P = NS); when treatment was initiated between 3 and 8 h after injury, MP treatment for 48 h resulted in significant improvements in motor scores at 6 wk (P = 0.04) and 6 mo (P = 0.01); MP administered for 48 h was associated with high rates of sepsis and pneumonia; no control group

Bracken et al. (1997)

Suggested Citation:"Appendix E Clinical Trials of Methylprednisolone." Institute of Medicine. 2005. Spinal Cord Injury: Progress, Promise, and Priorities. Washington, DC: The National Academies Press. doi: 10.17226/11253.
×

Description of Study

Evidence Class (Comments)

Results

Reference

1-yr follow-up of NASCIS III study

III (study design, data presentation, interpretation, and analysis flaws)

Recovery rates were equal in all three groups when treatment was initiated within 8 h; patients treated with MP for 24 h had diminished recovery; patients treated with MP for 48 h had increased motor recovery (P = 0.053)

Bracken et al. (1998)

Multicenter, prospective, randomized clinical trial of 106 ASCI patients treated with MP, nimopidine, neither, or both

III (inadequate statistical power)

No significant difference in neurological outcome between groups at 1 yr of follow-up; patients with incomplete ASCIs had significant improvements below the level of injury compared with that for patients with complete ASCIs (P < 0.0001); higher incidence of infectious complications among patients receiving corticosteroids (P = NS)

Pointillart et al. (2000)

Prospective, randomized, double-blind study comparing incidence of complications (56.5 and complications among 46 ASCI patients: 23 treated with MP and 23 treated with placebo

I

Patients treated with MP had a higher incidence of medical 34.8%, respectively); differences in respiratory complications (P = 0.009) and gastrointestinal bleed (P = 0.036) were most significant between groups; no data on neurological improvement

Matsumoto et al. (2001)

NOTE: Abbreviations: MP = methylprednisolone; ASCI = acute spinal cord injury; SCI = spinal cord injury; h = hour; mo = month; d = day; yr = year; NASCIS = National Acute Spinal Cord Injury Study; NS = not significant; TM = tirilazad mesylate; ICU = intensive care unit.

SOURCE: Reprinted with permission, from AANS/CNS, 2002. Copyright 2002 from Lippincott Williams & Wilkins.

Suggested Citation:"Appendix E Clinical Trials of Methylprednisolone." Institute of Medicine. 2005. Spinal Cord Injury: Progress, Promise, and Priorities. Washington, DC: The National Academies Press. doi: 10.17226/11253.
×

REFERENCES

AANS/CNS (American Association of Neurological Surgeons and the Congress of Neurological Surgeons). 2002. Pharmacological therapy after acute cervical spinal cord injury. Neurosurgery 50(3 Suppl): S63-72.


Bracken MB, Collins WF, Freeman DF, Shepard MJ, Wagner FW, Silten RM, Hellenbrand KG, Ransohoff J, Hunt WE, Perot PL Jr, et al. 1984. Efficacy of methylprednisolone in acute spinal cord injury. Journal of the American Medical Association 251(1): 45-52.

Bracken MB, Shepard MJ, Hellenbrand KG, Collins WF, Leo LS, Freeman DF, Wagner FC, Flamm ES, Eisenberg HM, Goodman JH, et al. 1985. Methylprednisolone and neurological function 1 year after spinal cord injury. Results of the National Acute Spinal Cord Injury Study. Journal of Neurosurgery 63(5): 704-713.

Bracken MB, Shepard MJ, Collins WF, Holford TR, Young W, Baskin DS, Eisenberg HM, Flamm E, Leo-Summers L, Maroon J. 1990. A randomized, controlled trial of methylprednisolone or naloxone in the treatment of acute spinal-cord injury. Results of the second National Acute Spinal Cord Injury Study. New England Journal of Medicine 322(20): 1405-1411.

Bracken MB, Shepard MJ, Collins WF Jr, Holford TR, Baskin DS, Eisenberg HM, Flamm E, Leo-Summers L, Maroon JC, Marshall LF, Perot PL Jr, Piepmeier J, Sonntag VKH, Wagner FC Jr, Wilberger JL, Winn HR, Young W. 1992. Methylprednisolone or naloxone treatment after acute spinal cord injury: 1-year follow-up data: Results of the second National Acute Spinal Cord Injury Study. Journal of Neurosurgery 76(1): 23-31.

Bracken MB, Shepard MJ, Holford TR, Leo-Summers L, Aldrich EF, Fazl M, Fehlings M, Herr DL, Hitchon PW, Marshall LF, Nockels RP, Pascale V, Perot PL Jr, Piepmeier J, Sonntag VKH, Wagner F, Wilberger JE, Winn HR, Young W. 1997. Administration of methylprednisolone for 24 or 48 hours or tirilazad mesylate for 48 hours in the treatment of acute spinal cord injury: Results of the third National Acute Spinal Cord Injury randomized controlled trial. Journal of the American Medical Association 277(20): 1597-1604.

Bracken MB, Shepard MJ, Holford TR, Leo-Summers L, Aldrich EF, Fazl M, Fehlings MG, Herr DL, Hitchon PW, Marshall LF, Nockels RP, Pascale V, Perot PL Jr, Piepmeier J, Sonntag VKH, Wagner F, Wilberger JE, Winn HR, Young W. 1998. Methylprednisolone or tirilazad mesylate administration after acute spinal cord injury: 1-year follow up: Results of the third National Acute Spinal Cord Injury randomized controlled trial. Journal of Neurosurgery 89(5): 699-706.


Galandiuk S, Raque G, Appel S, Polk HC Jr, Collins WF Jr, Trunkey D, Hoff JT, Howard J, Lucas CB, Patterson RH. 1993. The two-edged sword of large-dose steroids for spinal cord trauma. Annals of Surgery 218(4): 419-427.

George ER, Scholten DJ, Buechler CM, Jordan-Tibbs J, Mattice C, Albrecht RM, Turner W, Edwards M, Jacobs D. 1995. Failure of methylprednisolone to improve the outcome of spinal cord injuries. American Surgeon 61(8): 659-664.

Gerhart KA, Johnson RL, Menconi J, Hoffman RE, Lammertse DP. 1995. Utilization and effectiveness of methylprednisolone in a population-based sample of spinal cord injured persons. Paraplegia 33(6): 316-321.

Gerndt SJ, Rodriguez JL, Pawlik JW, Taheri PA, Wahl WL, Micheals AJ, Papadopoulos SM, Croce MA, Petersen SR, Hawkins ML. 1997. Consequences of high-dose steroid therapy for acute spinal cord injury. Journal of Trauma: Injury Infection & Critical Care 42(2): 279-284.


Matsumoto T, Tamaki T, Kawakami M, Yoshida M, Ando M, Yamada H. 2001. Early complications of high-dose methylprednisolone sodium succinate treatment in the follow-up of acute cervical spinal cord injury. Spine 26(4): 426-430.

Suggested Citation:"Appendix E Clinical Trials of Methylprednisolone." Institute of Medicine. 2005. Spinal Cord Injury: Progress, Promise, and Priorities. Washington, DC: The National Academies Press. doi: 10.17226/11253.
×

Pointillart V, Petitjean ME, Wiart L, Vital JM, Lassie P, Thicoipe M, Dabadie P. 2000. Pharmacological therapy of spinal cord injury during the acute phase. Spinal Cord 38(2): 71-76.

Poynton AR, O’Farrell DA, Shannon F, Murray P, McManus F, Walsh MG. 1997. An evaluation of the factors affecting neurological recovery following spinal cord injury. Injury 28(8): 545-548.

Suggested Citation:"Appendix E Clinical Trials of Methylprednisolone." Institute of Medicine. 2005. Spinal Cord Injury: Progress, Promise, and Priorities. Washington, DC: The National Academies Press. doi: 10.17226/11253.
×
Page 268
Suggested Citation:"Appendix E Clinical Trials of Methylprednisolone." Institute of Medicine. 2005. Spinal Cord Injury: Progress, Promise, and Priorities. Washington, DC: The National Academies Press. doi: 10.17226/11253.
×
Page 269
Suggested Citation:"Appendix E Clinical Trials of Methylprednisolone." Institute of Medicine. 2005. Spinal Cord Injury: Progress, Promise, and Priorities. Washington, DC: The National Academies Press. doi: 10.17226/11253.
×
Page 270
Suggested Citation:"Appendix E Clinical Trials of Methylprednisolone." Institute of Medicine. 2005. Spinal Cord Injury: Progress, Promise, and Priorities. Washington, DC: The National Academies Press. doi: 10.17226/11253.
×
Page 271
Suggested Citation:"Appendix E Clinical Trials of Methylprednisolone." Institute of Medicine. 2005. Spinal Cord Injury: Progress, Promise, and Priorities. Washington, DC: The National Academies Press. doi: 10.17226/11253.
×
Page 272
Suggested Citation:"Appendix E Clinical Trials of Methylprednisolone." Institute of Medicine. 2005. Spinal Cord Injury: Progress, Promise, and Priorities. Washington, DC: The National Academies Press. doi: 10.17226/11253.
×
Page 273
Suggested Citation:"Appendix E Clinical Trials of Methylprednisolone." Institute of Medicine. 2005. Spinal Cord Injury: Progress, Promise, and Priorities. Washington, DC: The National Academies Press. doi: 10.17226/11253.
×
Page 274
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An estimated 11,000 spinal cord injuries occur each year in the United States and more than 200,000 Americans suffer from maladies associated with spinal cord injury. This includes paralysis, bowel and bladder dysfunction, sexual dysfunction, respiratory impairment, temperature regulation problems, and chronic pain. During the last two decades, longstanding beliefs about the inability of the adult central nervous system to heal itself have been eroded by the flood of new information from research in the neurosciences and related fields. However, there are still no cures and the challenge of restoring function in the wake of spinal cord injuries remains extremely complex.

Spinal Cord Injury examines the future directions for research with the goal to accelerate the development of cures for spinal cord injuries. While many of the recommendations are framed within the context of the specific needs articulated by the New York Spinal Cord Injury Research Board, the Institute of Medicine’s panel of experts looked very broadly at research priorities relating to future directions for the field in general and make recommendations to strengthen and coordinate the existing infrastructure. Funders at federal and state agencies, academic organizations, pharmaceutical and device companies, and non-profit organizations will all find this book to be an essential resource as they examine their opportunities.

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