Cerebrospinal Fluid Drainage (CSFD) in Acute Spinal Cord Injury

NCT ID: NCT02495545

Last Updated: 2019-11-27

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

15 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-10-31

Study Completion Date

2019-10-25

Brief Summary

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The purpose of this Phase IIB randomized controlled trial is to evaluate the safety and efficacy of CSFD and to provide a preliminary clinical efficacy evaluation of the combination of CSFD and elevation of mean arterial pressure (MAP) in patients with acute spinal cord injury (SCI). The objectives of the trial are to evaluate (i) efficacy of reducing intrathecal pressure (ITP) by CSFD in patients with acute SCI; (ii) preliminary efficacy of combination of CSFD and elevation of MAP compared to elevation of MAP alone in improving neurologic motor outcomes in patients with acute SCI; and, (iii) safety of intensive CSFD in acute SCI patients.

Detailed Description

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Acute spinal cord injury (SCI) affects 10,000-14,000 persons per year in the United States (Burke, Linden et al. 2001). There are 150,000-300,000 persons living with significant disabilities from SCI at any given time (Bernhard, Gries et al. 2005). The average age of incident cases of SCI is 47 years and about 78% of the cases are males (DeVivo and Chen 2011). Estimates of the lifetime costs to care for someone with a SCI range from $325,000 to $1.35 million and the yearly cost to society reaches $8 billion (Sekhon and Fehlings 2001). With better long term care technologies, these costs are expected to continue to rise. Although there have been significant advances in accessibility for people with disabilities, the goal of medical science is to overcome the physiological barriers imposed by the injury itself and allow these individuals to regain their pre-injury level of neurological function (Rowland, Hawryluk et al. 2008). The injury to the spinal cord occurs in two phases. The first phase is the primary physical damage due to the impact energy of the compressive nature of the injury. The damage can be very complex with shearing of the axons, destruction of the cell bodies and disruption of the microvasculature at the site of injury. The secondary phase of the injury begins soon after the primary injury has occurred and can be influenced by many factors such as hypoxia, hypotension, and the extent of the primary injury. Spinal cord ischemia post-injury causes a significant increase in cell death and more significant neurological disability. Limiting tissue hypoperfusion post-injury can decrease the amount of cell death and axonal damage. Lumbar cerebrospinal fluid drainage (CSFD) together with increased mean arterial blood pressure (MAP) in the immediate post-injury period can reduce spinal cord tissue hypoperfusion. By reducing spinal cord hypoperfusion through elevation of MAP, less cell death and axonal damage will occur, leading to an improvement in neurological function. The feasibility of CSFD as a means for reducing the intrathecal pressure (ITP) in patients with acute SCI has been demonstrated in a small randomized controlled trial by Kwon et al (Kwon, Curt et al. 2009). The limitations were a small sample size, broad inclusion criteria, lack of statistical power calculation and restricted drainage regimen (maximum 10 mL per hour).

Conditions

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Spinal Cord Injury

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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CSFD with elevation of MAP

Subjects will receive CSFD and elevation of MAP. Treatments will be 120 hours (5 days) from time treatment is initiated (time 0), and within 24 hours of time of injury. Initiation of CSFD will occur after decompression (during surgery) with a target ITP of 10 mmHg. MAP elevation (norepinephrine drip; goal 100-110 mmHg) will start during surgery, simultaneously with CSFD. 10 mL of CSF will be collected daily for routine lab testing. Post-surgery subjects will be transferred to an intensive care unit (ICU) for duration of treatment or longer if clinically indicated. Target MAP will be sustained within 100-110 mmHg for 5 days. Norepinephrine drip will be used to maintain MAP goal. Subjects will receive other treatment per standard of care at the participating investigational sites.

Group Type EXPERIMENTAL

CSFD and elevation of MAP

Intervention Type PROCEDURE

Lumbar drain placement with CSFD with elevation of MAP

Maintenance of MAP

Subjects will receive elevation of MAP (norepinephrine drip; goal 85-90 mm Hg). Target MAP will be sustained within 85-90 mmHg in the control group for 5 days. Duration of elevation of MAP treatment will be 120 hours (5 days) from time treatment is (time 0). Subjects will receive the same treatment as the subjects in investigational arm except for the initiation of the CSFD and less aggressive MAP elevation. They will have a drain placed the same way as the experimental subjects. While drain is in place, 10 mL of cerebrospinal fluid will be collected daily for laboratory testing. After that, ITP will be monitored but CSFD will not be initiated. Subjects will receive other treatment per standard of care at participating investigational sites.

Group Type ACTIVE_COMPARATOR

Maintenance of MAP

Intervention Type PROCEDURE

Lumbar drain placement without CSFD and with maintenance of MAP

Interventions

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CSFD and elevation of MAP

Lumbar drain placement with CSFD with elevation of MAP

Intervention Type PROCEDURE

Maintenance of MAP

Lumbar drain placement without CSFD and with maintenance of MAP

Intervention Type PROCEDURE

Eligibility Criteria

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Inclusion Criteria

* Aged 18-75 years inclusive;
* Diagnosis of acute SCI;
* Injury is less than 24 hours old;
* ISNCSCI Impairment Scale Grade "A," "B" or "C" based upon first ISNCSCI evaluation after arrival to the hospital;
* Neurological level of injury between C4-C8 based upon first ISNCSCI evaluation after arrival to the hospital;
* Women of childbearing potential must have a negative serum β-hCG pregnancy test or a negative urine pregnancy test;
* Patient is willing to participate in the study;
* Informed consent document signed by patient or witnessed informed consent document;
* No contraindications for study treatment(s);
* Able to cooperate in the completion of a standardized neurological examination by ISNCSCI standards (includes patients who are on a ventilator).

Exclusion Criteria

* Injury arising from penetrating mechanism;
* Significant concomitant head injury defined by a Glasgow Coma Scale (GCS) score \< 14 with a clinically significant abnormality on a head CT (head CT required only for patients suspected to have a brain injury at the discretion of the investigator);
* Pre-existing neurologic or mental disorder which would preclude accurate evaluation and follow-up (i.e. Alzheimer's disease, Parkinson's disease, unstable psychiatric disorder with- hallucinations and/or delusions or schizophrenia);
* Prior history of SCI;
* Recent history (less than 1 year) of chemical substance dependency or significant psychosocial disturbance that may impact the outcome or study participation, in the opinion of the investigator;
* Is a prisoner;
* Participation in another clinical trial within the past 30 days;
* Acquired immune deficiency syndrome (AIDS) or AIDS-related complex;
* Active malignancy or history of invasive malignancy within the last five years, with the exception of superficial basal cell carcinoma or squamous cell carcinoma of the skin that has been definitely treated. Patients with carcinoma in situ of the uterine cervix treated definitely more than 1 year prior to enrollment may enter the study.
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Miami

OTHER

Sponsor Role collaborator

St. Joseph's Hospital and Medical Center, Phoenix

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Nicholas Theodore, MD

Role: PRINCIPAL_INVESTIGATOR

Barrow Neurological Institute, St. Joseph's Hospital and Medical Center

Locations

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University of Alabama School of Medicine Department of Neurosurgery

Birmingham, Alabama, United States

Site Status

Barrow Neurological Institute St. Joseph's Hospital and Medical Center

Phoenix, Arizona, United States

Site Status

University of Arizona Department of Surgery Division of Neurosurgery

Tucson, Arizona, United States

Site Status

Countries

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United States

References

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Amar AP, Levy ML. Pathogenesis and pharmacological strategies for mitigating secondary damage in acute spinal cord injury. Neurosurgery. 1999 May;44(5):1027-39; discussion 1039-40. doi: 10.1097/00006123-199905000-00052.

Reference Type BACKGROUND
PMID: 10232536 (View on PubMed)

Bernhard M, Gries A, Kremer P, Bottiger BW. Spinal cord injury (SCI)--prehospital management. Resuscitation. 2005 Aug;66(2):127-39. doi: 10.1016/j.resuscitation.2005.03.005.

Reference Type BACKGROUND
PMID: 15950358 (View on PubMed)

Brown PD, Davies SL, Speake T, Millar ID. Molecular mechanisms of cerebrospinal fluid production. Neuroscience. 2004;129(4):957-70. doi: 10.1016/j.neuroscience.2004.07.003.

Reference Type BACKGROUND
PMID: 15561411 (View on PubMed)

Burke DA, Linden RD, Zhang YP, Maiste AC, Shields CB. Incidence rates and populations at risk for spinal cord injury: A regional study. Spinal Cord. 2001 May;39(5):274-8. doi: 10.1038/sj.sc.3101158.

Reference Type BACKGROUND
PMID: 11438844 (View on PubMed)

Casha S, Christie S. A systematic review of intensive cardiopulmonary management after spinal cord injury. J Neurotrauma. 2011 Aug;28(8):1479-95. doi: 10.1089/neu.2009.1156. Epub 2010 Apr 8.

Reference Type BACKGROUND
PMID: 20030558 (View on PubMed)

Coselli JS, LeMaire SA, Koksoy C, Schmittling ZC, Curling PE. Cerebrospinal fluid drainage reduces paraplegia after thoracoabdominal aortic aneurysm repair: results of a randomized clinical trial. J Vasc Surg. 2002 Apr;35(4):631-9. doi: 10.1067/mva.2002.122024.

Reference Type BACKGROUND
PMID: 11932655 (View on PubMed)

DeVivo MJ, Chen Y. Trends in new injuries, prevalent cases, and aging with spinal cord injury. Arch Phys Med Rehabil. 2011 Mar;92(3):332-8. doi: 10.1016/j.apmr.2010.08.031.

Reference Type BACKGROUND
PMID: 21353817 (View on PubMed)

Dohrmann GJ, Wick KM, Bucy PC. Spinal cord blood flow patterns in experimental traumatic paraplegia. J Neurosurg. 1973 Jan;38(1):52-8. doi: 10.3171/jns.1973.38.1.0052. No abstract available.

Reference Type BACKGROUND
PMID: 4682352 (View on PubMed)

Fehlings MG, Tator CH, Linden RD. The relationships among the severity of spinal cord injury, motor and somatosensory evoked potentials and spinal cord blood flow. Electroencephalogr Clin Neurophysiol. 1989 Jul-Aug;74(4):241-59. doi: 10.1016/0168-5597(89)90055-5.

Reference Type BACKGROUND
PMID: 2471626 (View on PubMed)

Francel PC, Long BA, Malik JM, Tribble C, Jane JA, Kron IL. Limiting ischemic spinal cord injury using a free radical scavenger 21-aminosteroid and/or cerebrospinal fluid drainage. J Neurosurg. 1993 Nov;79(5):742-51. doi: 10.3171/jns.1993.79.5.0742.

Reference Type BACKGROUND
PMID: 8410254 (View on PubMed)

Guha A, Tator CH, Rochon J. Spinal cord blood flow and systemic blood pressure after experimental spinal cord injury in rats. Stroke. 1989 Mar;20(3):372-7. doi: 10.1161/01.str.20.3.372.

Reference Type BACKGROUND
PMID: 2922776 (View on PubMed)

Hadley MN, Walters BC. Introduction to the Guidelines for the Management of Acute Cervical Spine and Spinal Cord Injuries. Neurosurgery. 2013 Mar;72 Suppl 2:5-16. doi: 10.1227/NEU.0b013e3182773549. No abstract available.

Reference Type BACKGROUND
PMID: 23417174 (View on PubMed)

Hadley MN, Walters BC, Grabb PA, Oyesiku NM, Przybylski GJ, Resnick DK, Ryken TC, Mielke DH. Guidelines for the management of acute cervical spine and spinal cord injuries. Clin Neurosurg. 2002;49:407-98. No abstract available.

Reference Type BACKGROUND
PMID: 12506565 (View on PubMed)

Hickey R, Albin MS, Bunegin L, Gelineau J. Autoregulation of spinal cord blood flow: is the cord a microcosm of the brain? Stroke. 1986 Nov-Dec;17(6):1183-9. doi: 10.1161/01.str.17.6.1183.

Reference Type BACKGROUND
PMID: 3810718 (View on PubMed)

Horn EM, Theodore N, Assina R, Spetzler RF, Sonntag VK, Preul MC. The effects of intrathecal hypotension on tissue perfusion and pathophysiological outcome after acute spinal cord injury. Neurosurg Focus. 2008;25(5):E12. doi: 10.3171/FOC.2008.25.11.E12.

Reference Type BACKGROUND
PMID: 18980472 (View on PubMed)

Kindt GW. Autoregulation of spinal cord blood flow. Eur Neurol. 1971-1972;6(1):19-23. doi: 10.1159/000114459. No abstract available.

Reference Type BACKGROUND
PMID: 5005114 (View on PubMed)

Kobrine AI, Doyle TF, Martins AN. Autoregulation of spinal cord blood flow. Clin Neurosurg. 1975;22:573-81. doi: 10.1093/neurosurgery/22.cn_suppl_1.573.

Reference Type BACKGROUND
PMID: 810290 (View on PubMed)

Kobrine AI, Evans DE, Rizzoli HV. The role of the sympathetic nervous system in spinal cord autoregulation. Acta Neurol Scand Suppl. 1977;64:54-5. No abstract available.

Reference Type BACKGROUND
PMID: 409084 (View on PubMed)

Kwon BK, Curt A, Belanger LM, Bernardo A, Chan D, Markez JA, Gorelik S, Slobogean GP, Umedaly H, Giffin M, Nikolakis MA, Street J, Boyd MC, Paquette S, Fisher CG, Dvorak MF. Intrathecal pressure monitoring and cerebrospinal fluid drainage in acute spinal cord injury: a prospective randomized trial. J Neurosurg Spine. 2009 Mar;10(3):181-93. doi: 10.3171/2008.10.SPINE08217.

Reference Type BACKGROUND
PMID: 19320576 (View on PubMed)

Martirosyan NL, Feuerstein JS, Theodore N, Cavalcanti DD, Spetzler RF, Preul MC. Blood supply and vascular reactivity of the spinal cord under normal and pathological conditions. J Neurosurg Spine. 2011 Sep;15(3):238-51. doi: 10.3171/2011.4.SPINE10543. Epub 2011 Jun 10.

Reference Type BACKGROUND
PMID: 21663407 (View on PubMed)

Mokri B. The Monro-Kellie hypothesis: applications in CSF volume depletion. Neurology. 2001 Jun 26;56(12):1746-8. doi: 10.1212/wnl.56.12.1746.

Reference Type BACKGROUND
PMID: 11425944 (View on PubMed)

Palesch YY, Tilley BC, Sackett DL, Johnston KC, Woolson R. Applying a phase II futility study design to therapeutic stroke trials. Stroke. 2005 Nov;36(11):2410-4. doi: 10.1161/01.STR.0000185718.26377.07. Epub 2005 Oct 13.

Reference Type BACKGROUND
PMID: 16224086 (View on PubMed)

Piano G, Gewertz BL. Mechanism of increased cerebrospinal fluid pressure with thoracic aortic occlusion. J Vasc Surg. 1990 May;11(5):695-701. doi: 10.1067/mva.1990.19358.

Reference Type BACKGROUND
PMID: 2335835 (View on PubMed)

Ploumis A, Yadlapalli N, Fehlings MG, Kwon BK, Vaccaro AR. A systematic review of the evidence supporting a role for vasopressor support in acute SCI. Spinal Cord. 2010 May;48(5):356-62. doi: 10.1038/sc.2009.150. Epub 2009 Nov 24.

Reference Type BACKGROUND
PMID: 19935758 (View on PubMed)

Rowland JW, Hawryluk GW, Kwon B, Fehlings MG. Current status of acute spinal cord injury pathophysiology and emerging therapies: promise on the horizon. Neurosurg Focus. 2008;25(5):E2. doi: 10.3171/FOC.2008.25.11.E2.

Reference Type BACKGROUND
PMID: 18980476 (View on PubMed)

Royston P, Barthel FM, Parmar MK, Choodari-Oskooei B, Isham V. Designs for clinical trials with time-to-event outcomes based on stopping guidelines for lack of benefit. Trials. 2011 Mar 18;12:81. doi: 10.1186/1745-6215-12-81.

Reference Type BACKGROUND
PMID: 21418571 (View on PubMed)

Ryken TC, Hurlbert RJ, Hadley MN, Aarabi B, Dhall SS, Gelb DE, Rozzelle CJ, Theodore N, Walters BC. The acute cardiopulmonary management of patients with cervical spinal cord injuries. Neurosurgery. 2013 Mar;72 Suppl 2:84-92. doi: 10.1227/NEU.0b013e318276ee16. No abstract available.

Reference Type BACKGROUND
PMID: 23417181 (View on PubMed)

Sekhon LH, Fehlings MG. Epidemiology, demographics, and pathophysiology of acute spinal cord injury. Spine (Phila Pa 1976). 2001 Dec 15;26(24 Suppl):S2-12. doi: 10.1097/00007632-200112151-00002.

Reference Type BACKGROUND
PMID: 11805601 (View on PubMed)

Senter HJ, Venes JL. Loss of autoregulation and posttraumatic ischemia following experimental spinal cord trauma. J Neurosurg. 1979 Feb;50(2):198-206. doi: 10.3171/jns.1979.50.2.0198.

Reference Type BACKGROUND
PMID: 430132 (View on PubMed)

Smith AJ, McCreery DB, Bloedel JR, Chou SN. Hyperemia, CO2 responsiveness, and autoregulation in the white matter following experimental spinal cord injury. J Neurosurg. 1978 Feb;48(2):239-51. doi: 10.3171/jns.1978.48.2.0239.

Reference Type BACKGROUND
PMID: 624973 (View on PubMed)

Svensson LG, Crawford ES, Hess KR, Coselli JS, Safi HJ. Experience with 1509 patients undergoing thoracoabdominal aortic operations. J Vasc Surg. 1993 Feb;17(2):357-68; discussion 368-70.

Reference Type BACKGROUND
PMID: 8433431 (View on PubMed)

Sydes MR, Parmar MK, Mason MD, Clarke NW, Amos C, Anderson J, de Bono J, Dearnaley DP, Dwyer J, Green C, Jovic G, Ritchie AW, Russell JM, Sanders K, Thalmann G, James ND. Flexible trial design in practice - stopping arms for lack-of-benefit and adding research arms mid-trial in STAMPEDE: a multi-arm multi-stage randomized controlled trial. Trials. 2012 Sep 15;13:168. doi: 10.1186/1745-6215-13-168.

Reference Type BACKGROUND
PMID: 22978443 (View on PubMed)

Tator CH. Spine-spinal cord relationships in spinal cord trauma. Clin Neurosurg. 1983;30:479-94. doi: 10.1093/neurosurgery/30.cn_suppl_1.479. No abstract available.

Reference Type BACKGROUND
PMID: 6667588 (View on PubMed)

Tator CH, Fehlings MG. Review of the secondary injury theory of acute spinal cord trauma with emphasis on vascular mechanisms. J Neurosurg. 1991 Jul;75(1):15-26. doi: 10.3171/jns.1991.75.1.0015.

Reference Type BACKGROUND
PMID: 2045903 (View on PubMed)

Walters BC. Methodology of the Guidelines for the Management of Acute Cervical Spine and Spinal Cord Injuries. Neurosurgery. 2013 Mar;72 Suppl 2:17-21. doi: 10.1227/NEU.0b013e318276ed9a. No abstract available.

Reference Type BACKGROUND
PMID: 23417175 (View on PubMed)

Walters BC, Hadley MN, Hurlbert RJ, Aarabi B, Dhall SS, Gelb DE, Harrigan MR, Rozelle CJ, Ryken TC, Theodore N; American Association of Neurological Surgeons; Congress of Neurological Surgeons. Guidelines for the management of acute cervical spine and spinal cord injuries: 2013 update. Neurosurgery. 2013 Aug;60(CN_suppl_1):82-91. doi: 10.1227/01.neu.0000430319.32247.7f. No abstract available.

Reference Type BACKGROUND
PMID: 23839357 (View on PubMed)

Other Identifiers

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PHX 14BN084

Identifier Type: -

Identifier Source: org_study_id

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