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

NCT ID: NCT05707442

Last Updated: 2024-09-19

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 74 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-10-31
• Study Completion Date: 2026-12-31

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.

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.

Conditions

Idiopathic Intracranial Hypotension; Venous Sinus Stenosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

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.

Group Type: EXPERIMENTAL

Stent Implantation

Intervention Type: 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).

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%.

Group Type: ACTIVE_COMPARATOR

Acetazolamide-based medical therapy

Intervention Type: 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.

Weight loss

Intervention Type: BEHAVIORAL

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

Interventions

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).

Intervention Type: PROCEDURE

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.

Intervention Type: DRUG

Weight loss

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

Intervention Type: BEHAVIORAL

Eligibility Criteria

Inclusion Criteria

• Subject Eligibility Criteria

1. Diagnosis of IIH by modified Dandy criteria for more than 2 months

2. Lumbar puncture opening pressure ≥250 mmH₂O within 6 weeks before enrollment

3. Normal cerebrospinal fluid (CSF) composition

4. Neuroimaging showing normal brain parenchyma without hydrocephalus, mass, or any structural lesion and no evidence of meningeal enhancement on CT or MRI

5. Localized venous sinus stenosis (VSS) with stenotic degree ≥ 50% on DSA, and pressure gradient across stenosis ≥ 8 mmHg

6. Patients or their relatives signed written informed consent

• Ophthalmic Eligibility Criteria:

1. At least one eye had the presence of papilledema

2. 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%

3. Visual acuity above 20 / 200 (≥ 39 letters)

Exclusion Criteria

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

2. Visual loss due to other etiologies (eg, retinal drusen, retinal and optic neuropathy, cataracts, etc)

3. Other condition requiring the use of diuretics, steroids or other drugs to reduce intracranial pressure

4. DSA showed diffused venous sinus stenosis, cortical or deep vein stenosis

5. A history of severe thyroid disease and iodine allergy

6. Pregnant or lactating women

7. Severe cardiopulmonary, liver or kidney failure

8. Known hereditary or acquired haemorrhagic diathesis

9. Known hereditary or acquired thrombophilia

10. Platelet counts or coagulation abnormality

11. Major surgery or severe trauma or any traumatic brain injury within the previous 14 days

12. A history of cerebral hemorrhage, arteriovenous malformation, intracranial aneurysm or tumor

13. 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

14. Increased intracranial pressure due to other secondary factors

1. Current intraocular pressure > 28mmHg or previous intraocular pressure > 30mmHg

2. Refractive error spherical power greater than -6.0D or +6.0D and astigmatism greater than 3.0D, except for the following cases:

1. 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.

2. 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.

3. 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)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Beijing Tiantan Hospital

OTHER

Sponsor Role: lead

Responsible Party

Dapeng Mo

Clinical Professor of Interventional Neuroradiology, Department of Neurology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Dapeng Mo, MD

Role: PRINCIPAL_INVESTIGATOR

Beijing Tiantan Hospital

Zhongrong Miao, MD

Role: PRINCIPAL_INVESTIGATOR

Beijing Tiantan Hospital

Locations

Beijing Tiantan Hospital

Beijing, Beijing Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Xu Tong, MD

Role: CONTACT

dongri0514@sina.com

+8617611338800

Facility Contacts

Dapeng Mo, MD

Role: primary

modapeng1971@163.com

+8613691419036‬

Other Identifiers

HX-A-2022042

Identifier Type: -

Identifier Source: org_study_id