Evaluation of Tolerability and Efficacy of Erythropoietin (EPO) Treatment in Spinal Shock: Comparative Study Versus Methylprednisolone (MP)

This study has suspended participant recruitment.
(Italian Medicines Agency decision)
Sponsor:
Information provided by (Responsible Party):
Niguarda Hospital
ClinicalTrials.gov Identifier:
NCT00561067
First received: November 19, 2007
Last updated: February 20, 2012
Last verified: February 2012
  Purpose

The purpose of this study is to evaluate the tolerability and efficacy of erythropoietin (EPO) treatment in spinal shock in comparison with the methylprednisolone treatment (MP).


Condition Intervention Phase
Spinal Cord Injury
Drug: Erythropoietin
Drug: Methylprednisolone
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Evaluation of the Tolerability and Efficacy of Erythropoietin (EPO) Treatment in Spinal Shock: Comparative Study VS Methylprednisolone (MP)

Resource links provided by NLM:


Further study details as provided by Niguarda Hospital:

Primary Outcome Measures:
  • Improvement of ASIA Impairment Scale of at least 1 grade. Score on ASIA Scale and a ASIA Impairment Scale are an inclusion criteria, then at 3rd, 7th, 14th, 30th, 60th, 90th days [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Increase of ASIA motor/sensory scores at 3rd, 7th, 14th, 30th, 60th, 90th days [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
  • Functional autonomy with SCIM scores at 7th, 30th, 60th, 90th days [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
  • Spasticity with the Ashworth Scale, spasms with the PENN Scale and neurogenic pain with the VAS Scale at 7th, 14th days [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 100
Study Start Date: April 2008
Primary Completion Date: July 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
Methylprednisolone
Drug: Methylprednisolone
MP 30 mg/kg intravenous (iv) in the first hour, followed by 5.4 mg/kg/h for 23 hours if treatment is started within three hours after the spinal injury,or for 48 hours if treatment is started between three and eight hours (protocol NASCIS III, National Acute Spinal Cord Injury Study)
Experimental: 2
Erythropoietin
Drug: Erythropoietin
EPO 500 IU/kg diluted in 50 ml saline and infused in 30 minutes; treatment is started within eight hours after the spinal injury; the same drug dosage will be infused at 24 and 48 hours

Detailed Description:

Traumatic spinal cord injury (TSCI) is devastating for the patient and costly to society. Currently, methylprednisolone (MP) administered according NASCIS (III) protocol is the only therapy which has minor benefits and is accompanied by dangerous side effects. Any new treatment of TSCI that allows major recovery of function would be a significant advance in clinical care. Much of the motor and sensory paralysis following TSCI occurs because of a delayed and widespread oligodendrocyte apoptosis and demyelination of long spinal tracts. We have recently reported that erythropoietin (EPO) administration significantly attenuates such delayed secondary degeneration and promotes functional recovery in TSCI animal models. The research proposed is a multicenter trial involving the Italian Spinal Units that have developed a multidisciplinary experience on the management of TSCI. Primary objective of the study is to assess the superiority of EPO compared to MP in improving the clinical outcome of SCI (ASIA Impairment Scale); secondary objectives are: to assess the safety of EPO compared to MP, the effects on the motor and sensory functions and on improving functional autonomy, the influence on spasticity and neurogenic pain, and, the impact on surrogate end-points (Somatosensory Evoked Potentials and Magnetic Resonance Imaging).The study population is characterized by all patients with TSCI (ASIA Impairment Scale A or B) admitted to Italian Spinal Units: we estimate an enrolment of 100 subjects , 50 in each therapeutic arm. The study proposed is a single-blind randomized phase III parallel group trial in which eligible patients are randomized to one of the following treatment modalities: MP according to NASCIS III protocol or EPO iv (500 UI/kg within 8 hours after the SCI, dosage repeated at 24 and 48 hours). The duration of the study will be 24 months, with a 21-month maximum time to engage all the patients required by the power calculation.The primary end-point will be assessed using the Cochrane-Mantel-Haenzel test; the changes in the SEP (latency) and size of the MRI lesions using the Repeated Measures Analysis of Variance (ANOVA), the Ashworth, VAS, PENN, and SCIM scores with the parametric Wilcoxon's signed-ranks test. The effect of treatment on the primary end-point will be evaluated using a multivariate analysis model (binary logistic regression). The non-parametric alternative will be conducted if the assumption of normality will be not verified.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Traumatic SCI occurred within 8 hours
  • Hemodynamic stability at the time of treatment start (systolic blood pressure > 90 mmHg for at least 1 hour without massive infusion or vasopressor support for ongoing bleeding)
  • Neurological level between C5 and T12 (ASIA scale)
  • ASIA Impairment Scale: A or B
  • Informed consent

Exclusion Criteria:

  • SCI other than traumatic
  • SCI caused by edged weapons or fire arms
  • Traumatic SCI after 8 hours
  • Neurological level above C5 or below T12
  • ASIA Impairment Scale C, D, E
  • Uncontrolled arterial hypertension
  • Past or current cerebrovascular disease
  • Past or current acute myocardial infarction
  • History of thrombotic events
  • Other chronic cardiovascular disorders (cardiac arrhythmias, congestive heart failure)
  • History of peripheral arterial disease, polycythemia, porphyria, active malignancy
  • Previous or current neurological diseases with abnormal neurological examination
  • Suspected or definite pregnancy or lactation (requiring ßHCG confirmation)
  • Clinically relevant psychiatric disease
  • Known allergy to EPO
  • Hypersensitivity to human albumin
  • Acute or chronic renal failure
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00561067

Locations
Italy
A.O. Ospedale Ca' Granda
Milan, Italy, 20162
Sponsors and Collaborators
Niguarda Hospital
Investigators
Principal Investigator: Tiziana Redaelli, MD Azienda Ospedaliera Ospedale Niguarda Ca' Granda Milano
  More Information

No publications provided

Responsible Party: Niguarda Hospital
ClinicalTrials.gov Identifier: NCT00561067     History of Changes
Other Study ID Numbers: FARM6Y35XM
Study First Received: November 19, 2007
Last Updated: February 20, 2012
Health Authority: Italy: Ministry of Health

Keywords provided by Niguarda Hospital:
Spinal cord injury
spinal shock
erythropoietin

Additional relevant MeSH terms:
Shock
Spinal Cord Injuries
Wounds and Injuries
Pathologic Processes
Spinal Cord Diseases
Central Nervous System Diseases
Nervous System Diseases
Trauma, Nervous System
Epoetin alfa
Methylprednisolone acetate
Prednisolone acetate
Methylprednisolone
Methylprednisolone Hemisuccinate
Prednisolone
Prednisolone hemisuccinate
Prednisolone phosphate
Hematinics
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists

ClinicalTrials.gov processed this record on August 01, 2014