Mean Arterial Blood Pressure Treatment for Acute Spinal Cord Injury
| Status: | Recruiting |
|---|---|
| Conditions: | Hospital, Hospital, Neurology |
| Therapuetic Areas: | Neurology, Other |
| Healthy: | No |
| Age Range: | 16 - Any |
| Updated: | 11/3/2017 |
| Start Date: | February 2013 |
| End Date: | June 2019 |
| Contact: | W. Bradley Jacobs, MD |
| Email: | wbjacobs@ucalgary.ca |
| Phone: | 403-944-3406 |
Mean Arterial Pressure in Spinal Cord Injury (MAPS): Determination of Non-inferiority of a Mean Arterial Pressure Goal of 65 mmHg Compared to a Mean Arterial Pressure Goal of 85 mmHg in Acute Human Traumatic Spinal Cord Injury.
Current guidelines for the clinical management of acute spinal cord injury (SCI) recommend
maintenance of mean arterial blood pressure (MAP) at 85 to 90 mmHg for the first seven days
after SCI as a clinical option. Unfortunately, the medical evidence to support this
recommendation exists only at the clinical case series level (Class III data). Furthermore,
maintenance of sustained systemic hypertension, as per clinical guidelines, may be associated
with risks to the patient via adverse medical events. Given this equivocal evidence, the
investigators group has questioned the merit of sustained induced hypertension following
acute SCI and has previously conducted a randomized, prospective controlled feasibility study
to further examine this issue. This prior pilot study randomized patients with acute SCI to a
spinal cord perfusion pressure (SCPP = MAP - intrathecal pressure (ITP)) target of ≥ 75 mmHg
or to a control group (hypotension avoidance, MAP ≥ 65 mmHg). The primary endpoint measure
was defined as the change in American Spinal Injury Association (ASIA) motor score from
baseline. No difference in the primary outcome was noted at one-year post-SCI in this study.
In light of this pilot data, the investigators hypothesize that maintenance of normotension
(MAP ≥ 65mmHg) is not inferior to induced hypertension (MAP ≥ 85mmHg) for 7 days following
acute SCI. As such, the investigators propose to conduct a Phase III non-inferiority
prospective, randomized clinical trial in acute SCI patients. Subjects will be randomized
into one of two MAP management groups for 7 days; Group 1 will be managed with a target MAP ≥
65 mmHg, while Group 2 will be managed with a target MAP ≥ 85 mmHg. The primary endpoint will
be change in ASIA motor score from baseline at 12 months post injury. A difference of ≤10
ASIA motor points change from baseline between groups will be considered as non-inferiority.
Secondary endpoints will include ASIA sensory score, proportion of patients achieving a one
grade improvement in ASIA impairment scale, quality of life assessment (as measured by
Short-Form-36 [SF-36]) and functional outcome (as measured by the Spinal Cord Independence
Measure (SCIM) and Functional Independence Measure (FIM). These will be measured at baseline,
72 hours and 3, 6 and 12 months from injury. Adverse events will be meticulously recorded.
The information gleaned from this trial will provide valuable information for the acute
treatment of traumatic SCI and will serve the objective of optimizing current clinical
practice and thus maximizing medical and neurological outcome for individuals following acute
traumatic SCI.
maintenance of mean arterial blood pressure (MAP) at 85 to 90 mmHg for the first seven days
after SCI as a clinical option. Unfortunately, the medical evidence to support this
recommendation exists only at the clinical case series level (Class III data). Furthermore,
maintenance of sustained systemic hypertension, as per clinical guidelines, may be associated
with risks to the patient via adverse medical events. Given this equivocal evidence, the
investigators group has questioned the merit of sustained induced hypertension following
acute SCI and has previously conducted a randomized, prospective controlled feasibility study
to further examine this issue. This prior pilot study randomized patients with acute SCI to a
spinal cord perfusion pressure (SCPP = MAP - intrathecal pressure (ITP)) target of ≥ 75 mmHg
or to a control group (hypotension avoidance, MAP ≥ 65 mmHg). The primary endpoint measure
was defined as the change in American Spinal Injury Association (ASIA) motor score from
baseline. No difference in the primary outcome was noted at one-year post-SCI in this study.
In light of this pilot data, the investigators hypothesize that maintenance of normotension
(MAP ≥ 65mmHg) is not inferior to induced hypertension (MAP ≥ 85mmHg) for 7 days following
acute SCI. As such, the investigators propose to conduct a Phase III non-inferiority
prospective, randomized clinical trial in acute SCI patients. Subjects will be randomized
into one of two MAP management groups for 7 days; Group 1 will be managed with a target MAP ≥
65 mmHg, while Group 2 will be managed with a target MAP ≥ 85 mmHg. The primary endpoint will
be change in ASIA motor score from baseline at 12 months post injury. A difference of ≤10
ASIA motor points change from baseline between groups will be considered as non-inferiority.
Secondary endpoints will include ASIA sensory score, proportion of patients achieving a one
grade improvement in ASIA impairment scale, quality of life assessment (as measured by
Short-Form-36 [SF-36]) and functional outcome (as measured by the Spinal Cord Independence
Measure (SCIM) and Functional Independence Measure (FIM). These will be measured at baseline,
72 hours and 3, 6 and 12 months from injury. Adverse events will be meticulously recorded.
The information gleaned from this trial will provide valuable information for the acute
treatment of traumatic SCI and will serve the objective of optimizing current clinical
practice and thus maximizing medical and neurological outcome for individuals following acute
traumatic SCI.
Inclusion Criteria:
- Age greater than or equal to 16 years.
- Motor complete or incomplete (ASIA A, B, or C) acute traumatic SCI involving spinal
levels between C0 and T12.
- Written and informed consent from patient or a legally acceptable representative.
- Randomization and initiation of management protocol within 24 hours of injury.
- Reasonable expectation of availability to receive the full 7-day course of therapy and
be available for follow up evaluations.
Exclusion Criteria:
- Acute traumatic SCI > 24 hours old.
- Central cord syndrome, defined as ASIA C or D with mean lower extremity score greater
than upper extremity score.
- Isolated sensory deficit, motor intact.
- Isolated radicular motor deficit, defined as a unilateral motor deficit restricted to
a single myotome.
- Pregnancy.
- Associated conditions interfering with informed consent or outcome assessment
including closed head injury and major orthopedic injuries.
- Polytrauma: Abbreviated Injury Severity Score >3 in any area other than head.
- Known uncorrected severe coronary artery disease or evidence of active coronary
ischemia (ECG changes, positive troponin) will be excluded.
- Advanced cardiac, pulmonary, hepatic or liver disease; the former will be
operationally defined using NCI Toxicity Criteria (Grade 2 or higher).
- Allergy or other contraindication to norepinephrine.
- A known diagnosis of cancer (except basal cell cancer).
- Uncontrolled hypertension, defined as blood pressure persistently above 220 mmHg
systolic or 120 mmHg diastolic, despite antihypertensive therapy.
- Any patients living in a nursing home or supervised living centre. Patients must be
historically fully independent in all activities of daily living including banking,
shopping, cooking, toileting, showering and dressing.
- Any other medical condition, in the investigator's opinion, for which the patient
should not be included in the trial.
- Pre-existing and active major psychiatric or other chronic neurological disease.
- Patients who have a history of substance abuse or dependency within 12 months prior to
the study.
- Currently participating in another interventional investigational study.
We found this trial at
2
sites
4502 Medical Drive
San Antonio, Texas 78284
San Antonio, Texas 78284
(210) 567-7000
Principal Investigator: Mark Muir, MD
Phone: 210-743-4148
University of Texas Health Science Center at San Antonio The University of Texas Health Science...
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Calgary, Alberta
Principal Investigator: W. Bradley Jacobs, MD
Phone: 403-944-3406
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