Phase III Study of Minocycline in Acute Spinal Cord Injury
试验速览
- 阶段
- 3 期
- 入组人数
- 248
- 试验地点
- 7
- 主要终点
- ASIA Motor Recovery
研究概览
简要总结
The objective of this study is to assess the efficacy of IV minocycline in improving neurological and functional outcome after acute non-penetrating traumatic spinal cord injury (SCI).
The primary hypothesis is that intravenous minocycline twice daily (800 mg initial dose tapered to 400 mg by 100 mg at each dose then administered to the end of day 7) administered to subjects with acute traumatic non-penetrating cervical SCI starting within 12 hours of injury will improve motor recovery as assessed by the International Standards for Neurologic Classification of Spinal Cord Injury - ISNCSCI (a.k.a. ASIA) neurological examination measured between 3 months and 1 year post-injury, compared to placebo.
The secondary hypotheses are that the above minocycline treatment will also results in improvement in ASIA sensory improvement, in ASIA grade and in functional outcome as assessed by Spinal Cord Independence Measure (SCIM) and Short Form 36 (SF-36), compared to placebo. In addition the effect of minocycline on neurological and functional outcome after SCI is expected to be more pronounced in those subjects with motor incomplete SCI compared to those with motor compete SCI. A subgroup analysis will be undertaken to examine this hypothesis.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 16 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 16 or over
- •Acute traumatic non-penetrating cervical SCI involving neurological levels as defined by the ASIA neurological examination between C0 and C8 and resulting in a detectable change in the ASIA motor assessment
- •Patient English speaking and able to provide informed consent
- •Randomization and administration of first dose (drug or placebo) within 12 hours of injury.
排除标准
- •History of systemic lupus erythematosus (SLE)
- •Pre-existing hepatic or renal disease
- •Tetracycline hypersensitivity
- •Pregnancy or breast feeding
- •Isolated radicular motor deficit
- •Significant leucopenia (white blood cell count < 1⁄2 times the lower limit of normal) at screening
- •Elevated liver function tests (AST, ALT, alkaline phosphatase, or total bilirubin > 2 times the upper limit of normal) at screening
- •Presence of systemic disease that might interfere with patient safety, compliance or evaluation of the condition under study (e.g. insulin-dependent diabetes, Lyme disease, clinically significant cardiac disease, HIV, HTLV-1)
- •Associated traumatic conditions interfering with informed consent or outcome assessment (e.g. closed head injury, liver contusion)
- •Known uncorrected severe coronary artery disease or evidence of active coronary ischemia (ECG changes, positive Troponin) will be excluded, as they may not tolerate the standardized protocol for hemodynamic management
研究组 & 干预措施
Minocycline
Minocycline twice daily infused over 30 minutes through central venous access as follows 800 mg + 700 mg on Day 1, 600 mg + 500 mg on Day 2, and 400 mg thereafter from Day 3 thru Day 7
干预措施: Minocycline (Drug)
Minocycline
Minocycline twice daily infused over 30 minutes through central venous access as follows 800 mg + 700 mg on Day 1, 600 mg + 500 mg on Day 2, and 400 mg thereafter from Day 3 thru Day 7
干预措施: Surgical spinal cord decompression (Procedure)
Minocycline
Minocycline twice daily infused over 30 minutes through central venous access as follows 800 mg + 700 mg on Day 1, 600 mg + 500 mg on Day 2, and 400 mg thereafter from Day 3 thru Day 7
干预措施: Maintenance of minimum mean arterial pressure (MAP) (Procedure)
Placebo
250 ml normal saline and infused over 30 minutes through central venous access twice daily for 7 days
干预措施: Placebo (Drug)
Placebo
250 ml normal saline and infused over 30 minutes through central venous access twice daily for 7 days
干预措施: Surgical spinal cord decompression (Procedure)
Placebo
250 ml normal saline and infused over 30 minutes through central venous access twice daily for 7 days
干预措施: Maintenance of minimum mean arterial pressure (MAP) (Procedure)
结局指标
主要结局
ASIA Motor Recovery
时间窗: assessed at time points: day 1,3,7, week 3,6, month 3,6,12
Motor recovery (improvement from baseline examination) as assessed by the International Standards for Neurologic Classification of Spinal Cord Injury - ISNCSCI (a.k.a. ASIA) neurological examination measured between 3 months and 1 year post-injury, compared to placebo.
次要结局
- ASIA impairment grade(assessed at time points: day 1,3,7 week 3,6 month 3,6,12)
- ASIA sensory recovery(assessed at time points: day 1,3,7 week 3,6, months 3,6,12)
- Short Form 36 (SF-36)(assessed at time points: week 6, month 3,6,12)
- Spinal cord Independence measure (SCIM)(assessed at time points: week 6, month 3,6,12)
研究者
Steve Casha
Associate Professor
University of Calgary