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

NCT05707442 | Recruiting Phase 3 DMC

• 1 other identifier: HX-A-2022042
• Study Type: interventional
• Target: 74
• Locations: 1 country
• Sites: 1

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.

Conditions

Idiopathic Intracranial Hypotension; Venous Sinus Stenosis

Keywords

Idiopathic intracranial hypertension; Venous sinus stenosis; Stenting; Medical therapy; Randomized controlled trial

Outcome Measures

Primary Outcomes (1)

• Perimetric Mean Deviation (PMD)

  The change in perimetric mean deviation (PMD) from baseline to 6 month in the eye with the most severe visual loss at baseline.

  6 months

Secondary Outcomes (8)

• 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

Other Outcomes (5)

• Functional health status and quality of life:EuroQol five dimensions questionnaire (EQ-5D,0-100,higher scores mean a better outcome)

  6 months

• Cost-effectiveness analysis (mean costs per patient)

  6 months

• Cost-effectiveness analysis (quality-adjusted life years)

  6 months

Study Arms (2)

Stent Implantation

EXPERIMENTAL

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

Medical Therapy

ACTIVE COMPARATOR

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

Interventions

Stent Implantation PROCEDURE

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).

Stent Implantation

Acetazolamide-based medical therapy DRUG

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.

Medical Therapy

Weight loss BEHAVIORAL

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

Medical Therapy

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Beijing Tiantan Hospital: lead

Study Sites (1)

Beijing Tiantan Hospital

Beijing, Beijing Municipality, 100010, China

RECRUITING

MeSH Terms

Conditions

Pseudotumor Cerebri

Condition Hierarchy (Ancestors)

Intracranial Hypertension; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Dapeng Mo, MD

  Beijing Tiantan Hospital

  PRINCIPAL INVESTIGATOR

• Zhongrong Miao, MD

  Beijing Tiantan Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Xu Tong, MD

CONTACT

+8617611338800; dongri0514@sina.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Professor of Interventional Neuroradiology, Department of Neurology

Study Record Dates

• First Submitted: December 25, 2022
• First Posted: February 1, 2023
• Study Start: February 16, 2023
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): March 1, 2027
• Last Updated: February 10, 2026

Record last verified: 2026-02

Locations

CN (1)