Stent Implantation Versus Medical Therapy for Idiopathic IntracraniaL Hypertension (SIMPLE)

Sponsor

Beijing Tiantan Hospital (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT05707442

Collaborator

(none)

Enrollment

Location

Arms

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The aim of this study is to assess the efficacy of stent implantation versus medical therapy on idiopathic intracranial hypertension with venous sinus stenosis.

Condition or Disease	Intervention/Treatment	Phase
Idiopathic Intracranial Hypotension Venous Sinus Stenosis	Procedure: Stent Implantation Drug: Acetazolamide-based medical therapy Behavioral: Weight loss	Phase 3

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

74 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Stent Implantation Versus Medical Therapy for Idiopathic IntracraniaL Hypertension (SIMPLE)

Actual Study Start Date :

Oct 31, 2022

Anticipated Primary Completion Date :

Jun 1, 2024

Anticipated Study Completion Date :

Dec 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Procedure: Stent Implantation Aspirin (100 mg) and clopidogrel (75 mg) were administered 3-5 days before endovascular treatment. 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. Postoperatively, all patients received dual antiplatelet medications for 3 months and then received a single antiplatelet (either aspirin or clopidogrel).
Active Comparator: 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%.	Drug: Acetazolamide-based 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. Behavioral: Weight loss The weight loss program included a low-calorie diet (≤425 kcal/day) with a target weight loss of approximately 5-10%.

Arm

Intervention/Treatment

Experimental: 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.

Procedure: Stent Implantation

Aspirin (100 mg) and clopidogrel (75 mg) were administered 3-5 days before endovascular treatment. 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. Postoperatively, all patients received dual antiplatelet medications for 3 months and then received a single antiplatelet (either aspirin or clopidogrel).

Active Comparator: 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%.

Drug: Acetazolamide-based medical therapy

Behavioral: Weight loss

The weight loss program included a low-calorie diet (≤425 kcal/day) with a target weight loss of approximately 5-10%.

Outcome Measures

Primary Outcome Measures

Perimetric Mean Deviation (PMD) [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.

Secondary Outcome Measures

Cerebrospinal Fluid (CSF) Opening Pressure [6 months]
The change in intracranial pressure measured by lumbar puncture opening pressure from baseline to 6 months.
Papilledema Grade: Frisén grade(0-5 scores,and higher scores mean worse outcome) [6 months]
The change in papilledema measured by Frisén grade from baseline to 6 months
Retinal Nerve Fiber Layer Thickness [6 months]
The change in thickness of retinal nerve fiber layer measured by optical coherence tomography (OCT) from baseline to 6 months.
Total Retinal Thickness [6 months]
The change in thickness of total retina measured by optical coherence tomography (OCT) from baseline to 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]
The change in vision measured by National Eye Institute-Visual Function Questionnaire-25 (NEI-VFQ-25) from baseline to 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]
The change in vision measured by 10-item neuro-ophthalmic supplement to the National Eye Institute-Visual Function Questionnaire-25 (NEI-VFQ-25)from baseline to 6 months.
Headache: Headache Impact Test-6 (HIT-6, minimum and maximum values: 36-78 points, higher scores mean greater headache severity) [6 months]
The change in headache measured by Headache Impact Test-6 (HIT-6) questionnaire from baseline to 6 months.
Pulsatile tinnitus: Tinnitus Handicap Inventory (THI, minimum and maximum values: 0-100 points, higher scores mean more serious tinnitus disability) [6 months]
The change in pulsatile tinnitus from baseline to 6 months；pulsatile tinnitus was assessed using the Tinnitus Handicap Inventory (THI), which is a self-report measure that can be used in a busy clinical practice to quantify the impact of tinnitus on daily living.

Other Outcome Measures

Functional health status and quality of life:EuroQol five dimensions questionnaire (EQ-5D,0-100,higher scores mean a better outcome) [6 months]
The change in functional health status and quality of life measured by EuroQol five dimensions questionnaire (EQ-5D) from baseline to 6 months
Cost-effectiveness analysis (mean costs per patient) [6 months]
The indicator of cost-effectiveness analysis refers to the mean costs per patient.
Cost-effectiveness analysis (quality-adjusted life years) [6 months]
The indicator of cost-effectiveness analysis refers to the quality-adjusted life years.
Cost-effectiveness analysis (the cost saving per extra patient with a good outcome) [6 months]
The indicator of cost-effectiveness analysis refers to the cost saving per extra patient with a good outcome.
Cost-effectiveness analysis (the cost saving per additional quality-adjusted life year) [6 months]
The indicator of cost-effectiveness analysis refers to the cost saving per additional quality-adjusted life year.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 60 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Subject Eligibility Criteria

Diagnosis of IIH by modified Dandy criteria 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)

Exclusion Criteria:

Subject Exclusion Criteria

Previous surgery for IIH, including optic nerve sheath fenestration (ONSF), CSF shunting, decompressive craniectomy or venous sinus stenting
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)