Subarachnoid Hemorrhage, Spontaneous
Conditions
Brief summary
This is a Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Study of SFX-01 in Subarachnoid Haemorrhage, with exploratory evaluations of efficacy.
Detailed description
The study is a randomised, double-blind, parallel-group design comparing SFX-01 (300 mg) taken orally as capsules or as a suspension via a nasogastric tube (NG) twice-daily for up to 28 days versus placebo in 90 patients who have had SAH and present within 48 hours of ictus. Subjects will receive SFX-01/Placebo in order to review potential outcomes investigating the long-term complications of SAH such as Delayed Cerebral Ischaemia, as reflected by Trans-Cranial Doppler (TCD) readings. The objective is to demonstrate safety and search for signals of efficacy in patients that have had SAH. A sub-study will be conducted in up to 12 patients where an External Ventricular Drain (EVD) fitted; serial CSF samples will be taken pre- & post-dose on two occasions to determine pharmacokinetics of Sulforaphane in CSF in comparison with plasma pharmacokinetics. Sub-study patients will undergo all other procedures (with the exception of lumbar puncture). Treatment duration is up to 28 days; follow up duration is 28 days, three and six months. The planned trial period is 24 months.
Interventions
DRUGSFX-01
An intervention releasing sulforaphane.
DRUGPlacebo
Placebo otherwise identical to Active product
Sponsors
Evgen Pharma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Patients with radiological evidence of spontaneous SAH 2. Fisher grade 3 or 4 on CT 3. Definitive treatment of aneurysm has not been ruled out 4. Previously living independently 5. In the opinion of the investigator, the delay from ictus to randomisation and initiation of trial medication will not exceed 48 hours 6. Aged 18 to 80 years 7. In the opinion of the investigator it will be possible to obtain Informed Consent from the Patient, Personal Legal Representative or Professional Legal representative within 24 hours of first dose
Exclusion criteria
1. Traumatic SAH 2. Fisher grade 1 or 2 3. SAH diagnosed on lumbar puncture with no evidence of blood on CT 4. Decision not to treat aneurysm has been made 5. Plan to withdraw treatment 6. Significant kidney disease as defined as plasma creatinine ≥2.5mg/dL (221 µmol/l) 7. Liver disease as defined as total bilirubin ≥2-fold the upper limit of normal; (ULN) as measured by the local laboratory 8. Females who are pregnant or lactating. 9. Participants enrolled in another interventional research trial in the last 30 days 10. Patients for whom it is known, at the time of screening, that clinical follow-up will not be feasible Patients unwilling to use two forms of contraception (one of which being a barrier method) 30 days for men and 90 days for women after last IMP dose
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with treatment-related adverse events as assessed by Common Toxicity Criteria | up to 28 days | To evaluate the safety of up to 28 days of SFX-01 dosed at up to 96 mg Sulforaphane (SFN) per day |
| Maximum CSF Concentration [Cmax], | up to 28 days | To detect the presence of SFN in Cerebrospinal Fluid (CSF) |
| Number of participants with treatment related reduction in middle cerebral artery (MCA) peak flow velocity following Subarachnoid Haemorrhage (SAH) measured by trans cranial doppler ultrasound | up to 28 days | To determine if a minimum of 7 days treatment with SFX-01 reduces Middle Cerebral Artery (MCA) peak flow velocity following Subarachnoid Haemorrhage (SAH). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serum Haptoglobin levels | Up to 28 days | To determine if up to 28 days treatment with SFX-01 increases serum haptoglobin (HP) levels following SAH |
| modified Rankin Scale | up to 180 days post ictus | To determine if a minimum of 7 days treatment with SFX-01 improves clinical outcome following SAH as measured using the modified Rankin Scale assessed at 7 , 28, 90 and 180 days post ictus. |
| Delayed Cerebral Ischaemia | Up to 28 days | To determine if up to 28 days treatment with SFX-01 can reduce the incidence of Delayed Cerebral Ischaemia (DCI) following SAH. |
| Plasma PK | up to 28 days | To determine plasma SFN levels (and its metabolites) with treatment with SFX-01 (300mg bid). |
| CSF drug levels | up to 14 days | To determine CSF drug levels following treatment with SFX-01 (300mg bid). |
Countries
United Kingdom
Outcome results
None listed