Spinal Cord InjuryPhase 3NCT00561067
Evaluation of Tolerability and Efficacy of Erythropoietin (EPO) Treatment in Spinal Shock: Comparative Study Versus Methylprednisolone (MP)
A Phase 3 study testing Erythropoietin and Methylprednisolone in people with Spinal Cord Injury, run by Niguarda Hospital at 1 site in Italy.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Spinal Cord Injury
- What is being tested?
- Erythropoietin and Methylprednisolone
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteItaly
- Study dates
- Apr 2008to Jul 2008
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Evaluation of the Tolerability and Efficacy of Erythropoietin (EPO) Treatment in Spinal Shock: Comparative Study VS Methylprednisolone (MP)
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).
Read the 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.
- Conditions
- Spinal Cord Injury
- Being tested
- Erythropoietin, Methylprednisolone
- Keywords
- Spinal cord injury, spinal shock, erythropoietin
- Medical subject headings
- Spinal Cord Injuries
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ErythropoietinDrug
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
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)
| Study group | Role | What they receive |
|---|---|---|
| 1 | Active comparator | Methylprednisolone Receives: Drug: Methylprednisolone |
| 2 | Experimental | Erythropoietin Receives: Drug: Erythropoietin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 3 months
Secondary outcomes (3)
Increase of ASIA motor/sensory scores at 3rd, 7th, 14th, 30th, 60th, 90th days
Measured: 3 months
Functional autonomy with SCIM scores at 7th, 30th, 60th, 90th days
Measured: 3 months
Spasticity with the Ashworth Scale, spasms with the PENN Scale and neurogenic pain with the VAS Scale at 7th, 14th days
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Nov 2007 (estimated)
- Study startApr 2008
- Primary completionJul 2008
- Study completionJul 2008
Why it stopped: Italian Medicines Agency decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Spinal Cord InjuryStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Niguarda Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Tiziana Redaelli, MD, Principal investigator, Azienda Ospedaliera Ospedale Niguarda Ca' Granda Milano
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00561067
- Sponsor's protocol ID
- FARM6Y35XM
- Status last verified
- Mar 2019
- First submitted
- 19 Nov 2007
- Last updated
- 14 Mar 2019
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 14 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of the Tolerability and Efficacy of Erythropoietin (EPO) Treatment in Spinal Shock: Comparative Study VS Methylprednisolone (MP)
- ClinicalTrials.gov ID
- NCT00561067
- Acronym / sponsor ID
- FARM6Y35XM
- Conditions
- Spinal Cord Injury
- Keywords
- Spinal cord injury, spinal shock, erythropoietin
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Italian Medicines Agency decision
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Niguarda HospitalUniversity, hospital or other
- Study start
- Apr 2008 (actual)
- Primary completion
- Jul 2008 (actual)
- Study completion
- Jul 2008 (actual)
- First posted
- 20 Nov 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Active comparator | Drug: MethylprednisoloneMethylprednisolone |
| 2 | Experimental | Drug: ErythropoietinErythropoietin |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (17 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ErythropoietinEPO 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 | Drug | 2 |
| MethylprednisoloneMP 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) | Drug | 1 |
Primary outcome
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
3 secondary outcomes
Increase of ASIA motor/sensory scores at 3rd, 7th, 14th, 30th, 60th, 90th days
Time frame: 3 months
Functional autonomy with SCIM scores at 7th, 30th, 60th, 90th days
Time frame: 3 months
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
Results and safety
The study was stopped early (reason given: Italian Medicines Agency decision). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Mar 2019.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Tiziana Redaelli, MD principal investigator
Azienda Ospedaliera Ospedale Niguarda Ca' Granda Milano
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Erythropoietin and Methylprednisolone in people with Spinal Cord Injury, run by Niguarda Hospital at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 14 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Italian Medicines Agency decision). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Mar 2019.