IIH - Idiopathic Intracranial Hypertension
Conditions
Keywords
DVSS, dural venous sinus stent, stent, shunt, intracranial pressure, stenosis, papilloedema, visual loss, OCT, RNFL
Brief summary
Background and study aims Idiopathic intracranial hypertension (IIH) is a neurological condition characterised by increased pressure inside the skull, called intracranial pressure (ICP). It is more common in women of reproductive age with obesity. Common symptoms of IIH include headaches, blurred vision and ringing in the ears. If left untreated, the disorder may cause blindness. The majority of patients with IIH are managed with weight loss and medications. Fewer than 10% of patients develop progressive visual loss and require urgent intervention to reduce ICP and preserve vision. This trial will compare the two most common interventions performed in the UK and evaluate their clinical and cost-effectiveness. The first is called cerebrospinal fluid (CSF) shunting and involves a procedure where a thin tube called a shunt is implanted in the body to drain brain fluid. The second is called dural venous sinus stenting (DVSS) and involves a procedure where a metallic mesh tube called a stent is implanted inside a brain blood vessel. Both procedures can preserve vision, but there is no strong evidence to support one over the other. Participants will have the same chance to be treated with CSF shunting or DVSS. The aim of the trial is to know which intervention is the most effective to save the vision and the most cost-effective. Who can participate? Adults with a diagnosis of IIH at risk of permanent sight loss What does the study involve? The trial will be conducted in NHS hospitals located in England, Wales and Scotland. Participants are randomly allocated to undergo cerebrospinal fluid (CSF) shunting or dural venous sinus stenting (DVSS). Afterwards the participants will be asked to attend 11 hospital appointments and one telephone appointment. This follow-up will take 2 years from start to finish. Participants will be closely monitored for any side effects and potential device failure, and for changes in vision, headaches and quality of life. The researchers will also collect health data from NHS Digital (the national custodian of NHS health and social care data). What are the possible benefits and risks of participating? There are no direct benefits from taking part in the trial but the information gained from this trial may help improve treatment for adults with IIH in the future. Participants may be seen more often and/or feel more supported as a consequence of their involvement in the trial. As with any intervention, there are risks and complications, but there are no additional disadvantages or risks involved in taking part in this trial. Both CSF shunting and stenting are treatments for IIH (shunting is widely used internationally, and in some hospitals, stenting is used as part of the standard of care). Participants require an intervention to prevent sight loss. None of these treatments is experimental but at present, there is not enough information to determine which treatment is most suitable and provides the higher level of health benefits to the individual. Where is the study run from? University of Birmingham (UK) When is the study starting and how long is it expected to run for? The first site opened in July 2023, and the last patient last visit is expected in May 2028 Who is funding the study? National Institute for Health Research (NIHR, grant number: NIHR131211) (UK) Who is the main contact? IIH Intervention Trial manager, IIHIntervention@trials.bham.ac.uk (UK)
Interventions
DEVICECSF shunt
CSF shunt may be ventriculoperitoneal (VP) or lumboperitoneal (LP) at the discretion of the treating medical team.
DEVICEDVSS
Dural Venous Sinus Stent. Exact make and model of device not mandated by protocol.
Sponsors
University of Birmingham
National Institute for Health Research, United Kingdom
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 63 Years
Healthy volunteers
No
Inclusion criteria
1. Diagnosis of IIH by the IIH consensus guidelines with papilloedema and at risk of visual loss. 2. Presence of papilloedema (Frisén grade ≥ 3) in at least one eye 3. Age 18 to \< 64 years at the time of consent. 4. Patients must be suitable for and willing to proceed with both CSF shunting (VP or Lumboperitoneal shunts only) and DVSS. 5. Able to provide written informed consent.
Exclusion criteria
1. Presence of current venous sinus thrombosis on diagnostic brain imaging by either MRI, MRV or CTV 2. Previous surgery for IIH including, optic nerve sheath fenestration, CSF shunting procedures, sub-temporal decompression and DVSS. 3. Previous bariatric surgery within the last 3 months 4. Patients with a past ophthalmic history, except refraction error, affecting the eligible eyes (study eyes) that could affect the vision. 5. Patient is, at the time of signing the informed consent, a user of recreational or illicit drugs (including marijuana) or has had a recent history (within the last year) of drug or alcohol abuse or dependence, in the opinion of the investigator. 6. History of any clinically significant disease or disorder which, in the opinion of the investigator, may either put the subject at risk because of participation in the study, or influence the results or the subject's ability to participate in the study. 7. Have participated in any other interventional study within 30 days prior to the screening visit (of note participation in the IIH Life database or other observational studies will not prevent enrolment to this study). 8. Previous randomisation for treatment in the present study. 9. Pregnant. 10. Absolute or serious contraindication to standard anti-thrombotic regimen peri and post stenting. 11. Secondary causes of raised intracranial pressure. (Refer to Protocol appendix 3 for additional information.) 12. History of significant documented iodine-based contrast allergy. 13. History of documented allergy to nitinol or nickel. 14. Absolute or serious contraindication for general anaesthesia. 15. Previous diagnosis of a hypercoagulable state (Factor V Leiden, Protein C or S deficiency, Anticardiolipin antibodies, Lupus anticoagulant, B2-glycoprotein-1 antibodies, or Hyperhomocysteinaemia). 16. Currently requiring full anticoagulation for other medical reasons, such as atrial fibrillation, artificial valves, deep vein thrombosis or pulmonary embolism. 17. Documented prior non-traumatic intracranial haemorrhage. 18. History of deep vein thrombosis or pulmonary embolism (within the last 24 months). 19. History of severe carotid atherosclerotic disease. 20. History of heart failure, dilated cardiomyopathy or congenital heart disease, etc. that are assessed as at high thrombotic risk. 21. Presence of intracranial vascular malformation considered clinically symptomatic (current or within 24 months). 22. Anatomical anomaly of the venous sinus which would prevent safe catheterisation and stenting (e.g. multi-channel sinus).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Global thickness of the retinal nerve fibre layer (RNFL) over 6 months, as measured by OCT | 6 months | Global thickness of the retinal nerve fibre layer (RNFL) over 6 months, as measured in micrometers by OCT |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Global thickness of the retinal nerve fibre layer (RNFL) | 12 months, 24 months | Global thickness of the retinal nerve fibre layer (RNFL) measured in micrometers by OCT over 12 and 24 months |
| Total retinal nerve fibre layer thickness | 6, 12 and 24 months | Total retinal thickness measured in micrometers by OCT |
| Disc global volume | 6, 12 and 24 months | Disc global volume measured in micrometers cubed by OCT |
| Disc central thickness | 6, 12 and 24 months | Disc central thickness measured by OCT (micrometers) |
| Disc maximum height | 6, 12 and 24 months | Disc maximum height measured by OCT (micrometers) |
| Macular ganglion cell layer volume | over 6, 12 and 24 months | Macular ganglion cell layer volume as measured by OCT in micrometers cubed |
| Visual acuity | Over 6, 12 and 24 months | Visual acuity, measured by logarithm of the minimum angle or resolution (LogMAR) units. Visual acuity (VA) is measured on the logMAR scale by sight tests in clinic using Early treatment diabetic retinopathy study (ETDRS) charts at 4 meters. Values are taken for each eye separately, both uncorrected, and corrected with glasses or contact lenses, and can range from 0, which represents perfect vision i.e. 20/20 (values of-0.1 and -0.2 are also possible representing better than perfect vision), to +2 which represents near blindness i.e. 20/2000. Increases in logMAR represent deterioration in vision. |
| Humphrey Visual Fields (HVF) Perimetric Mean Deviation (PMD) | Over 6, 12 and 24 months | Humphrey Visual Fields (HVF) 24-2 SITA standard visual field test measured by Perimetric Mean Deviation (PMD). Visual threshold is the intensity of stimulus seen 50% of the time at each location. Higher numbers mean the patient was able to see a more attenuated light, and thus has more sensitive vision at that location. The numerical total deviation map compares the patient's visual sensitivity to an average normal individual of the same age. It is useful to compare with age-matched normal thresholds as sensitivity normally decreases gradually with age. Positive values represent areas of the field where the patient can see dimmer stimuli than the average individual of that age. Negative values represent decreased sensitivity from normal. Reliability indices, including fixation losses, false positives, and false negatives are also included. |
| Proportion of patients re-presenting to hospital within 30 days post-intervention | 30 days | Proportion of patients re-presenting to hospital within 30 days post-intervention. Percentage |
| Proportion of patients being re-admitted to hospital within 30 days post-intervention. | 30 days | Proportion of patients being re-admitted to hospital within 30 days post-intervention. Percentage |
| Proportion of major complication, defined as the incidence of complications graded between III and V or major anaesthesia problems (including complications from revision procedures) according to the Clavien-Dindo classification of surgical complications | over 6, 12 and 24 months | Measured by the Clavien-Dindo classification of surgical complications. The Clavien-Dindo scale is a validated, 5-grade, ordinal scale used to grade surgical complications based on the therapeutic interventions required to manage them. It provides a standardised, objective method for reporting postoperative morbidity (grades I-IV) and mortality (grade V), with increasing severity based on the level of care, from minor bedside treatment to ICU-level support or death. |
| Proportion with minor complications, defined as Clavien-Dindo grade I-II during hospital stay. | Over 6, 12 and 24 months | Measured by the Clavien-Dindo scale; grade I-II. The Clavien-Dindo scale is a validated, 5-grade, ordinal scale used to grade surgical complications based on the therapeutic interventions required to manage them. It provides a standardized, objective method for reporting postoperative morbidity (grades I-IV) and mortality (grade V), with increasing severity based on the level of care, from minor bedside treatment to ICU-level support or death. |
| Proportion of patients requiring revision in whom the revision intervention is the same as the primary intervention | over 6, 12 and 24 months | Percentage |
| Proportion of patients requiring revision in whom the revision intervention crosses over to the alternative intervention | over 6, 12 and 24 months | percentage |
| Time to first revision | measured in days over 6, 12 and 24 months | measured in days from day of intervention to day of first revision |
| Number of revisions per patient | over 6, 12 and 24 months | number |
| Proportion of patients with Adverse Events grade 3 or above measured by the CTCAE version 5. | Over 6, 12 and 24 months | CTCAE v5. In the CTCAE, symptoms are categorised by organ system, ranging from mild (Grade 1) to death (Grade 5) |
| Monthly headache days | over 6, 12, and 24 months | number of days per month with headache reported |
| Monthly moderate to severe headache days | over 6, 12 and 24 months | Measured by number of headache days per month with a severity greater than or equal to 4. 0-10 scale where 0 is no headache and 10 is the worst imaginable headache. Scores between 4 and 10 will be considered moderate to severe. |
| Headache severity (numeric rating scale (NRS) 0-10) | over 6, 12 and 24 months | Headache severity measured by (numeric rating scale (NRS) 0-10) where 0 is no headache and 10 is the worst headache |
| Moderate to severe headache severity (NRS greater than or equal to 4) | Over 6, 12 and 24 months | Headache severity measured by (numeric rating scale (NRS) 0-10) where 0 is no headache and 10 is the worst headache. Moderate to severe headache severity (NRS greater than or equal to 4) |
| Monthly use of acute headache analgesics | over 6, 12 and 24 months | number of days per month where analgesics are used to treat headaches as documented on the concomitant medication form and the headache diary. |
| Quality of Recovery 15 (QoR-15) measured at time of discharge | At time of discharge (usually within 7 days of intervention) | QoR 15 is a validated, 15-item patient-reported questionnaire used to measure the quality of recovery after surgery and anaesthesia, with a maximum score of 150 indicating excellent recovery. |
| Satisfaction with intervention (5-point Likert scale) measured at time of discharge | At time of discharge (usually within 7 days) | 5-point Likert scale with 1 - Very Unsatisfied and 5 - Very Satisfied |
| Visual Function Questionnaire (NEI-VFQ-25 with 10-Item Neuro-Ophthalmic Supplement) | Over 6, 12 and 24 months | measure of visual function using a composite score ranging from 0-100, where higher scores indicate better function. |
| Headache Impact Test (HIT-6) | Over 6, 12 and 24 months | 6-question tool that measures the impact of headaches on daily life, producing a total score between 36 and 78. Higher scores indicate greater severity. Scores of 60+ indicate a very severe, 56-59 a substantial, 50-55 some, and 49 or less little to no impact. |
| 36-item Short form health survey (SF-36v2) | Over 6, 12 and 24 months | A patient-reported tool measuring eight health domains, scoring them from 0 to 100, where 0 represents maximum limitations and 100 represents no health restrictions |
| EuroQol 5 dimension 5 level survey (EQ5D-5L) | Over 6, 12 and 24 months | The EQ-5D-5L consists of 2 pages: the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems (1), slight problems (2), moderate problems (3), severe problems (4) and extreme problems (5). The patient is asked to indicate his/her health state by ticking the box next to the most appropriate statement in each of the five dimensions. This decision results in a 1-digit number that expresses the level selected for that dimension. The digits for the five dimensions can be combined into a 5-digit number that describes the patient's health state. The EQ VAS records the patient's self-rated health on a vertical visual analogue scale from 0 "worst imaginable health" to 100 "best imaginable health" |
| Time to return to work (if working) | Measured in days from date of intervention for the duration of follow up: reported over 6, 12 and 24 months | fewer days to return to work is better than more days to return to work |
| Work Productivity and Activity Impairment Questionnaire - General Health (WPAI-GH) | Over 6, 12 and 24 months | The WPAI measures absenteeism, presenteeism and activity impairment attributable to ill-health over the preceding 7 days. The WPAI calculates percentage impairment (maximum 100%) with higher numbers representing greater work impairment. |
| Proportion of patients requiring ICP lowering medication above a clinically relevant threshold | Over 6, 12 and 24 months | Measured as a percentage of patients reporting use of ICP lowering medications |
| Healthcare resource use questionnaire | over 6, 12 and 24 months | Designed to calculate how much healthcare resource is used by each patient since the last clinic visit. This assesses the economic impact of IIH and will record any major differences in cost per QALY gained on each arm of the trial |
Countries
United Kingdom
Contacts
CONTACTAlexandra Sinclair, MBChB, FRCP, PhD
CONTACTIIH Intervention Mailbox
Outcome results
None listed