IIH Intervention: A Clinical Trial Comparing 2 Treatments (Shunts and Stents) Evaluation Of Clinical Effectiveness And Cost Effectiveness

University of Birmingham80 enrolled

Overview

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)

Eligibility

Sex: ALLMin age: 18 YearsMax age: 63 Years

Medical Language ↔ Plain English

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).

Locations (15)

The Queen Elizabeth Hospital

Birmingham, United Kingdom

RECRUITING

Bristol Eye Hospital

Bristol, United Kingdom

NOT_YET_RECRUITING

Southmead Hospital

Bristol, United Kingdom

NOT_YET_RECRUITING

Addenbrooke's Hospital

Cambridge, United Kingdom

RECRUITING

University Hospital of Wales

Cardiff, United Kingdom

RECRUITING

Princess Alexandra Eye Pavillion

Edinburgh, United Kingdom

RECRUITING

Queen Elizabeth University Hospital

Glasgow, United Kingdom

RECRUITING

Royal Hull Infirmary

Hull, United Kingdom

RECRUITING

Leeds General Infirmary

Leeds, United Kingdom

RECRUITING

King's College Hospital

London, United Kingdom

RECRUITING

...and 5 more locations

Outcomes

Primary Outcomes

Global thickness of the retinal nerve fibre layer (RNFL) over 6 months, as measured by OCT

Global thickness of the retinal nerve fibre layer (RNFL) over 6 months, as measured in micrometers by OCT

Time frame: 6 months

Secondary Outcomes

Global thickness of the retinal nerve fibre layer (RNFL)

Global thickness of the retinal nerve fibre layer (RNFL) measured in micrometers by OCT over 12 and 24 months

Time frame: 12 months, 24 months

Total retinal nerve fibre layer thickness

Total retinal thickness measured in micrometers by OCT

Time frame: 6, 12 and 24 months

Disc global volume

Disc global volume measured in micrometers cubed by OCT

Time frame: 6, 12 and 24 months

Disc central thickness

Disc central thickness measured by OCT (micrometers)

Time frame: 6, 12 and 24 months

Disc maximum height

Disc maximum height measured by OCT (micrometers)

Time frame: 6, 12 and 24 months

Macular ganglion cell layer volume

Macular ganglion cell layer volume as measured by OCT in micrometers cubed

Time frame: over 6, 12 and 24 months

Visual acuity

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.

Time frame: Over 6, 12 and 24 months

Humphrey Visual Fields (HVF) Perimetric Mean Deviation (PMD)

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.

Time frame: Over 6, 12 and 24 months

Proportion of patients re-presenting to hospital within 30 days post-intervention

Proportion of patients re-presenting to hospital within 30 days post-intervention. Percentage

Time frame: 30 days

Proportion of patients being re-admitted to hospital within 30 days post-intervention.

Proportion of patients being re-admitted to hospital within 30 days post-intervention. Percentage

Time frame: 30 days

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

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.

Time frame: over 6, 12 and 24 months

Proportion with minor complications, defined as Clavien-Dindo grade I-II during hospital stay.

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.

Time frame: Over 6, 12 and 24 months

Proportion of patients requiring revision in whom the revision intervention is the same as the primary intervention

Percentage

Time frame: over 6, 12 and 24 months

Proportion of patients requiring revision in whom the revision intervention crosses over to the alternative intervention

percentage

Time frame: over 6, 12 and 24 months

Time to first revision

measured in days from day of intervention to day of first revision

Time frame: measured in days over 6, 12 and 24 months

Number of revisions per patient

number

Time frame: over 6, 12 and 24 months

Proportion of patients with Adverse Events grade 3 or above measured by the CTCAE version 5.

CTCAE v5. In the CTCAE, symptoms are categorised by organ system, ranging from mild (Grade 1) to death (Grade 5)

Time frame: Over 6, 12 and 24 months

Monthly headache days

number of days per month with headache reported

Time frame: over 6, 12, and 24 months

Monthly moderate to severe headache days

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.

Time frame: over 6, 12 and 24 months

Headache severity (numeric rating scale (NRS) 0-10)

Headache severity measured by (numeric rating scale (NRS) 0-10) where 0 is no headache and 10 is the worst headache

Time frame: over 6, 12 and 24 months

Moderate to severe headache severity (NRS greater than or equal to 4)

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)

Time frame: Over 6, 12 and 24 months

Monthly use of acute headache analgesics

number of days per month where analgesics are used to treat headaches as documented on the concomitant medication form and the headache diary.

Time frame: over 6, 12 and 24 months

Quality of Recovery 15 (QoR-15) measured at time of discharge

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.

Time frame: At time of discharge (usually within 7 days of intervention)

Satisfaction with intervention (5-point Likert scale) measured at time of discharge

5-point Likert scale with 1 - Very Unsatisfied and 5 - Very Satisfied

Time frame: At time of discharge (usually within 7 days)

Visual Function Questionnaire (NEI-VFQ-25 with 10-Item Neuro-Ophthalmic Supplement)

measure of visual function using a composite score ranging from 0-100, where higher scores indicate better function.

Time frame: Over 6, 12 and 24 months

Headache Impact Test (HIT-6)

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.

Time frame: Over 6, 12 and 24 months

36-item Short form health survey (SF-36v2)

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

Time frame: Over 6, 12 and 24 months

EuroQol 5 dimension 5 level survey (EQ5D-5L)

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 frame: Over 6, 12 and 24 months

Time to return to work (if working)

fewer days to return to work is better than more days to return to work

Time frame: Measured in days from date of intervention for the duration of follow up: reported over 6, 12 and 24 months

Work Productivity and Activity Impairment Questionnaire - General Health (WPAI-GH)

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.

Time frame: Over 6, 12 and 24 months

Proportion of patients requiring ICP lowering medication above a clinically relevant threshold

Measured as a percentage of patients reporting use of ICP lowering medications

Time frame: Over 6, 12 and 24 months

Healthcare resource use questionnaire

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

Time frame: over 6, 12 and 24 months

IIH Intervention: A Clinical Trial Comparing 2 Treatments (Shunts and Stents) Evaluation Of Clinical Effectiveness And Cost Effectiveness

Overview

Conditions

Interventions

Eligibility

Locations (15)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts