A Randomized Controlled, Open-Label, Rater-Blinded Pragmatic Trial, Treatment of Inflammatory Myelitis and Optic Neuritis With Early vs Rescue Plasma Exchange (TIMELY-PLEX)
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- Mayo Clinic
- 入组人数
- 382
- 试验地点
- 35
- 主要终点
- High contrast visual acuity
研究概览
简要总结
The purpose of this research is to evaluate if early vs rescue Therapeutic Plasma Exchange (PLEX) treatment algorithm leads to better visual outcomes in severe Optic Neuritis and leads to better neurological disability outcomes in severe Transverse Myelitis.
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
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Study Population and Setting
- •The proposal will recruit participants presenting to participating sites with severe ON or severe TM to two separate sub-trials. The detailed inclusion and
排除标准
- •for each sub-trial are listed below:
- •Optic Neuritis Sub-Trial:
- •Inclusion criteria:
- •≥18 years of age
- •MRI orbits demonstrating evidence of new T2 hyperintensity and/or post-gadolinium contrast enhancement of the optic nerve(s) and meeting the clinical criteria for Optic Neuritis
- •Visual acuity 20/200 or worse
- •Within 8 days of onset of visual symptoms
- •Able to initiate PLEX within 72h of the first dose of HDCS (if randomized to the "Early PLEX" treatment arm)
- •Able to sign and date informed consent form
- •Willingness to comply with all study procedures and availability for the duration of the study
- •Exclusion criteria:
- •Evidence of prior episode of optic neuritis in the affected eye (by history or ophthalmological evaluation)
- •Ophthalmological comorbidity that would significantly affect best corrected visual acuity or visual fields
- •Pregnancy
- •Presence of any contraindication to receiving HDCS or PLEX, including, but not limited to, hemodynamic instability, significant bleeding/coagulopathy, or sepsis.
- •Any medical condition that, in the opinion of the investigator, may interfere with the patient's participation in the trial, pose any added risk for the patient, or confound the assessment of the patient (including but not limited to concurrent neurological disease and/or medical comorbidity)
- •Treatment with any investigational agent within 6 months of baseline or five half-lives of the investigational agent (whichever is longer)
- •Ongoing/prior treatment with immune-modulating/immunosuppressive therapy including:
- •Mycophenolate mofetil, azathioprine, methotrexate, fingolimod, siponimod, ponesimod, ozanimod, tocilizumab, satralizumab, eculizumab or ravulizumab within 3 months of randomization
- •Anti-CD20 (rituximab, ocrelizumab, ofatumumab, ublituximab) or anti-CD19 (inebilizumab) therapy within 6 months of randomization
- •Intravenous or subcutaneous immune globulin within 3 months of randomization
- •Plasma exchange within 3 months of randomization
- •Interferon-beta, glatiramer acetate, fumarates (dimethyl fumarate, monomethyl fumarate, diroximel fumarate) within 1 month of randomization
- •Teriflunomide use within prior 24 months
- •Systemic corticosteroid therapy (intravenous or oral; excluding inhaled or topical corticosteroids) within 1 month of randomization
- •Any previous treatment with alemtuzumab, cladribine, mitoxantrone or cyclophosphamide
- •Previous treatment with any immune-modulating or immunosuppressive therapy not mentioned above within 6 months of randomization or five-half-lives (whichever is longer)
- •Transverse Myelitis Sub-Trial:
- •Inclusion criteria:
- •≥18 years of age
- •Diagnosis of Transverse Myelitis (defined based on modified criteria adapted from the 2002 Transverse Myelitis Consortium Working Group; ALL are required)
- •Development of sensory, motor and/or autonomic symptomatology attributable to spinal cord dysfunction
- •Onset of symptoms to nadir >12 hours
- •Exclusion of extra-axial compressive etiology by neuroimaging
- •Demonstration of inflammation within the spinal cord by presence of intramedullary T2 lesion (post-gadolinium enhancing OR non-enhancing) on MRI
- •Expanded Disability Status Scale [EDSS] ≥3.0 (excluding visual and cerebral functional systems)
- •EDSS Pyramidal Functional System Score ≥ 2
- •Within 8 days of onset of motor symptoms
- •Able to initiate PLEX within 48h of the first dose of HDCS (if randomized to the "Early PLEX" treatment arm)
- •Able to sign and date informed consent form
- •Willingness to comply with all study procedures and availability for the duration of the study
- •Exclusion criteria:
- •Pre-existing ambulatory, motor, sensory, or bowel/bladder disability of any cause that could confound trial assessments
- •Fulfillment of possible, probable or definite spinal cord infarction diagnosis per proposed diagnostic criteria (Zalewski et al. JAMA Neurology 2018)
- •History of radiation to the spine
- •Pregnancy
- •High clinical suspicion for infectious etiology of myelitis (e.g., fever, rash or other findings)
- •Presence of any contraindication to receiving HDCS or PLEX, including, but not limited to, hemodynamic instability, significant bleeding/coagulopathy, or sepsis.
- •Any medical condition that, in the opinion of the investigator, may interfere with the patient's participation in the trial, pose any added risk for the patient, or confound the assessment of the patient (including but not limited to concurrent neurological disease and/or medical comorbidity)
- •Treatment with any investigational agent within 24 weeks of baseline or five half-lives of the investigational agent (whichever is longer)
- 另有 9 项未显示
研究组 & 干预措施
Optic Neuritis (ON) "Rescue PLEX"
Adult participants presenting within 8 days of symptom onset with severe Optic Neuritis (ON) (visual acuity of 20/200 or worse
干预措施: High-dose corticosteroids (HDCS) (Drug)
Optic Neuritis (ON) "Early PLEX"
Adult participants presenting within 8 days of symptom onset with severe Optic Neuritis (ON) (visual acuity of 20/200 or worse
干预措施: High-dose corticosteroids (HDCS) and PLEX (Drug)
Transverse Myelitis "Rescue PLEX"
Adult participants presenting within 8 days of symptom onset with severe Transverse Myelitis (TM) (expanded Disability Status Scale [EDSS] of 3.0 or worse)
干预措施: High-dose corticosteroids (HDCS) (Drug)
Transverse Myelitis "Early PLEX"
Adult participants presenting within 8 days of symptom onset with severe Transverse Myelitis (TM) (expanded Disability Status Scale [EDSS] of 3.0 or worse)
干预措施: High-dose corticosteroids (HDCS) and PLEX (Drug)
结局指标
主要结局
High contrast visual acuity
时间窗: 6 months
The Optic Neuritis subjects will have high contrast visual acuity measured by ETDRS 100% high-contrast Sloan letter charts. A high contrast visual acuity of 20/20 is considered "normal," a high contrast visual acuity of 20/40 or better is required to be able to drive without restrictions, and a high contrast visual acuity of 20/200 or worse is considered legally blind.
Expanded Disability Status Score (EDSS)
时间窗: 6 months
The level of disability in Transverse Myelitis subjects will be assessed using the Expanded Disability Status Scale (EDSS). The EDSS assesses various neurological functional systems, including pyramidal, cerebellar, brainstem, sensory, bowel and bladder, visual, and cereberal functions and ranges from 0 (normal neurological examination) to 10 (death). Higher scores indicate greater disability. Visual and cerebral functional system scores will be excluded from the EDSS calculation for quantification of Transverse Myelitis-related disability.
High contrast visual acuity
时间窗: 6 months
The Optic Neuritis subjects will have high contrast visual acuity measured by ETDRS 100% high-contrast Sloan letter charts. A high contrast visual acuity of 20/20 is considered "normal," a high contrast visual acuity of 20/40 or better is required to be able to drive without restrictions, and a high contrast visual acuity of 20/200 or worse is considered legally blind.
Expanded Disability Status Score (EDSS)
时间窗: 6 months
The level of disability in Transverse Myelitis subjects will be assessed using the Expanded Disability Status Scale (EDSS). The EDSS assesses various neurological functional systems, including pyramidal, cerebellar, brainstem, sensory, bowel and bladder, visual, and cereberal functions and ranges from 0 (normal neurological examination) to 10 (death). Higher scores indicate greater disability. Visual and cerebral functional system scores will be excluded from the EDSS calculation for quantification of Transverse Myelitis-related disability.
次要结局
- Macular ganglion cell-inner plexiform layer (GCIPL) thicknesses(6 months)
- Low contrast (2.5%) visual acuity(6 months)
- Peri-papillary retinal nerve fiber layer (RNFL thickness)(6 months)
- Hardy Rand and Rittler (HRR) color plates(6 months)
- National Eye Institute (NEI) 10-Item Neuro-Ophthalmic Supplement(6 months)
- Ambulatory disability(6 months)
- Manual dexterity (Nine-Hole Peg Test)(6 months)
- Patient Determined Disease Steps (PDDS)(6 months)
- Spinal Cord Injury Quality of Life questionnaire (SCI-QoL)(6 months)
- PLEX Complications(2 weeks, 1 month)
- National Eye Institute (NEI) Visual Function Questionnaire (VFQ)-25(6 months)