Stent Implantation Versus Medical Therapy for Idiopathic IntracraniaL Hypertension (SIMPLE)
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 74
- 试验地点
- 1
- 主要终点
- Perimetric Mean Deviation (PMD)
研究概览
简要总结
The aim of this study is to assess the efficacy of stent implantation versus medical therapy on idiopathic intracranial hypertension with venous sinus stenosis.
详细描述
The SIMPLE is a multicentered, prospective, randomized, open-label, blinded end-point clinical trial. A total of 74 patients with idiopathic intracranial hypertension (IIH) and venous sinus stenosis (VSS) for more than 2 months will be enrolled. Patients fulfilling all of the inclusion criteria and none of the exclusion criteria will be randomized 1:1 into two groups (stenting or medical therapy) after offering informed content.
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
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subject Eligibility Criteria
- •Diagnosis of IIH by modified Dandy criteria about for more than 2 months
- •Lumbar puncture opening pressure ≥250 mmH₂O within 6 weeks before enrollment
- •Normal cerebrospinal fluid (CSF) composition
- •Neuroimaging showing normal brain parenchyma without hydrocephalus, mass, or any structural lesion and no evidence of meningeal enhancement on CT or MRI
- •Localized venous sinus stenosis (VSS) with stenotic degree ≥ 50% on DSA, and pressure gradient across stenosis ≥ 8 mmHg
- •Patients or their relatives signed written informed consent
- •Ophthalmic Eligibility Criteria:
- •At least one eye had the presence of papilledema
- •At least one eye of visual field loss: PMD ranging from - 2dB and below; decreased visual function on automated perimetry was reproducible with a false-positive rate of no more than 15%
- •Visual acuity above 20 / 200 (≥ 39 letters)
排除标准
- •Subject Exclusion Criteria
- •Previous surgery for IIH, including optic nerve sheath fenestration (ONSF), CSF shunting, decompressive craniectomy or venous sinus stenting
- •Progressive or rapid visual loss needed urgent surgical intervention; if delay>24-48 h consider interim lumbar drain (for rapid visual loss only).Surgical options to consider: CSF diversion or optic nerve sheath fenestration
- •Visual loss due to other etiologies (eg, retinal drusen, retinal and optic neuropathy, cataracts, etc)
- •Other condition requiring the use of diuretics, steroids or other drugs to reduce intracranial pressure
- •DSA showed diffused venous sinus stenosis, cortical or deep vein stenosis
- •A history of severe thyroid disease and iodine allergy
- •Pregnant or lactating women
- •Severe cardiopulmonary, liver or kidney failure
- •Known hereditary or acquired haemorrhagic diathesis
- •Known hereditary or acquired thrombophilia
- •Platelet counts or coagulation abnormality
- •Major surgery or severe trauma or any traumatic brain injury within the previous 14 days
- •A history of cerebral hemorrhage, arteriovenous malformation, intracranial aneurysm or tumor
- •Other life threatening illness (eg, advanced cancer) likely to lead to death within a few months; the physical, psychological and social status of patients may affect follow-up (eg, drug addiction, advanced malignant disease, no telephone, no family, etc); cannot tolerate general anesthesia
- •Increased intracranial pressure due to other secondary factors
- •Ophthalmic Exclusion Criteria:
- •Current intraocular pressure > 28mmHg or previous intraocular pressure > 30mmHg
- •Refractive error spherical power greater than -6.0D or +6.0D and astigmatism greater than 3.0D, except for the following cases:
- •Myopia of - 6.0D to - 8.0D with the following: 1)There was no myopia related disease that can lead to decreased vision under the eyeground microscope (eg, scleral staphyloma, retinal thinning at the posterior pole, and moderate to severe disc tilt); 2) The patient wore contact lenses of appropriate degree for all visual field examinations.
- •Hyperopia of +6.0D to +8.0D with the following: 1) The presence of a well characterized peri optic disc edematous halo, as opposed to crowded small optic discs or other features of decreased visual acuity associated with hyperopic changes, was at the discretion of the site investigator or reading center leader (or his designee); 2) The patient wore contact lenses of appropriate degree for all visual field examinations.
- •Examination visible or past medical history known to have large optic disc drusen (persistent optic disc edema can present with small optic disc drusen, as low numbers are acceptable for inclusion and to be determined by the investigator to be unrelated to vision loss)
研究组 & 干预措施
Stent Implantation
The endovascular procedure was performed under general anesthesia. Intravenous heparin was administered during the stent procedure to increase the activated clotting time to > 250 s. An 8F guiding catheter was delivered to the internal jugular vein near the skull base. A 6F Navien intermediate guide catheter was then placed into the distal transverse sinus near the torcula through the 8F guiding catheter. A microguidewire was navigated across the stenosis using a microcatheter, followed by the deployment of a self-expanding stent (eg, Precise or Wallstent) adjusted to the normal sinus venous diameter adjacent to the stenosis. Venography and manometry were performed after the procedure.
干预措施: Stent Implantation (Procedure)
Medical Therapy
The medical treatment consisted of acetazolamide (0.5-4 g/day) and short-term mannitol (bolus of 0.25-1 g/kg body weight) for a duration of about 1 week or repeated lumbar punctures to reduce intracranial pressure (20 mL each), as well as analgesics for headaches. The initial dosage of acetazolamide was 0.5 g daily in two divided doses, followed by dosage increases of one tablet every week up to a maximum dosage of 4 g/day. The dosage escalation was stopped if the participant had papilledema grade <1 in both eyes, unless the presence of other symptoms such as headache or tinnitus suggested that the dosage escalation should continue. The dosage for the participants who were unable to tolerate the study drug was decreased gradually to a minimum of one half tablet daily. In addition, the weight loss program included a low-calorie diet (≤425 kcal/day) with a target weight loss of approximately 5-10%.
干预措施: Acetazolamide-based medical therapy (Drug)
Medical Therapy
The medical treatment consisted of acetazolamide (0.5-4 g/day) and short-term mannitol (bolus of 0.25-1 g/kg body weight) for a duration of about 1 week or repeated lumbar punctures to reduce intracranial pressure (20 mL each), as well as analgesics for headaches. The initial dosage of acetazolamide was 0.5 g daily in two divided doses, followed by dosage increases of one tablet every week up to a maximum dosage of 4 g/day. The dosage escalation was stopped if the participant had papilledema grade <1 in both eyes, unless the presence of other symptoms such as headache or tinnitus suggested that the dosage escalation should continue. The dosage for the participants who were unable to tolerate the study drug was decreased gradually to a minimum of one half tablet daily. In addition, the weight loss program included a low-calorie diet (≤425 kcal/day) with a target weight loss of approximately 5-10%.
干预措施: Weight loss (Behavioral)
结局指标
主要结局
Perimetric Mean Deviation (PMD)
时间窗: 6 months
The change in perimetric mean deviation (PMD) from baseline to 6 month in the eye with the most severe visual loss at baseline.
次要结局
- Headache: Headache Impact Test-6 (HIT-6, minimum and maximum values: 36-78 points, higher scores mean greater headache severity)(6 months)
- Pulsatile tinnitus: Tinnitus Handicap Inventory (THI, minimum and maximum values: 0-100 points, higher scores mean more serious tinnitus disability)(6 months)
- Cerebrospinal Fluid (CSF) Opening Pressure(6 months)
- Papilledema Grade: Frisén grade(0-5 scores,and higher scores mean worse outcome)(6 months)
- Retinal Nerve Fiber Layer Thickness(6 months)
- Total Retinal Thickness(6 months)
- Visual Acuity: National Eye Institute-Visual Function Questionnaire-25 (NEI-VFQ-25, minimum and maximum values: 0-100 points, higher scores mean a better visual function)(6 months)
- Visual Acuity: 10-item neuro-ophthalmic supplement to the National Eye Institute-Visual Function Questionnaire-25 (NEI-VFQ-25) (minimum and maximum values: 0-100 points, higher scores mean a better visual function)(6 months)
研究者
Dapeng Mo
Clinical Professor of Interventional Neuroradiology, Department of Neurology
Beijing Tiantan Hospital