Back to resultsSFX-01 After Subarachnoid Haemorrhage (SAS)
Primary Purpose
Subarachnoid Hemorrhage, Spontaneous
Status
Completed
Phase
Phase 2
Locations
United Kingdom
Study Type
Interventional
Intervention
SFX-01
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Subarachnoid Hemorrhage, Spontaneous
Eligibility Criteria
Inclusion Criteria:
- Patients with radiological evidence of spontaneous SAH
- Fisher grade 3 or 4 on CT
- Definitive treatment of aneurysm has not been ruled out
- Previously living independently
- In the opinion of the investigator, the delay from ictus to randomisation and initiation of trial medication will not exceed 48 hours
- Aged 18 to 80 years
- 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:
- Traumatic SAH
- Fisher grade 1 or 2
- SAH diagnosed on lumbar puncture with no evidence of blood on CT
- Decision not to treat aneurysm has been made
- Plan to withdraw treatment
- Significant kidney disease as defined as plasma creatinine ≥2.5mg/dL (221 µmol/l)
- Liver disease as defined as total bilirubin ≥2-fold the upper limit of normal; (ULN) as measured by the local laboratory
- Females who are pregnant or lactating.
- Participants enrolled in another interventional research trial in the last 30 days
- 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
Sites / Locations
- Southampton General Hospital
- Western General Hospital
- The Royal London Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
SFX-01
Placebo
Arm Description
300mg bid for up to 28 days.
300mg placebo bid for up to 28 days
Outcomes
Primary Outcome Measures
Number of participants with treatment-related adverse events as assessed by Common Toxicity Criteria
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],
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
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 Outcome Measures
modified Rankin Scale
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.
Plasma PK
To determine plasma SFN levels (and its metabolites) with treatment with SFX-01 (300mg bid).
CSF drug levels
To determine CSF drug levels following treatment with SFX-01 (300mg bid).
Serum Haptoglobin levels
To determine if up to 28 days treatment with SFX-01 increases serum haptoglobin (HP) levels following SAH
Delayed Cerebral Ischaemia
To determine if up to 28 days treatment with SFX-01 can reduce the incidence of Delayed Cerebral Ischaemia (DCI) following SAH.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02614742
Brief Title
SFX-01 After Subarachnoid Haemorrhage
Acronym
SAS
Official Title
SFX-01 After Subarachnoid Haemorrhage
Study Type
Interventional
2. Study Status
Record Verification Date
July 2019
Overall Recruitment Status
Completed
Study Start Date
April 2016 (Actual)
Primary Completion Date
September 2019 (Actual)
Study Completion Date
November 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Evgen Pharma
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Subarachnoid Hemorrhage, Spontaneous
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
90 (Actual)
8. Arms, Groups, and Interventions
Arm Title
SFX-01
Arm Type
Active Comparator
Arm Description
300mg bid for up to 28 days.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
300mg placebo bid for up to 28 days
Intervention Type
Drug
Intervention Name(s)
SFX-01
Other Intervention Name(s)
Sulforadex
Intervention Description
An intervention releasing sulforaphane.
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Cyclodextrin
Intervention Description
Placebo otherwise identical to Active product
Primary Outcome Measure Information:
Title
Number of participants with treatment-related adverse events as assessed by Common Toxicity Criteria
Description
To evaluate the safety of up to 28 days of SFX-01 dosed at up to 96 mg Sulforaphane (SFN) per day
Time Frame
up to 28 days
Title
Maximum CSF Concentration [Cmax],
Description
To detect the presence of SFN in Cerebrospinal Fluid (CSF)
Time Frame
up to 28 days
Title
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
Description
To determine if a minimum of 7 days treatment with SFX-01 reduces Middle Cerebral Artery (MCA) peak flow velocity following Subarachnoid Haemorrhage (SAH).
Time Frame
up to 28 days
Secondary Outcome Measure Information:
Title
modified Rankin Scale
Description
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.
Time Frame
up to 180 days post ictus
Title
Plasma PK
Description
To determine plasma SFN levels (and its metabolites) with treatment with SFX-01 (300mg bid).
Time Frame
up to 28 days
Title
CSF drug levels
Description
To determine CSF drug levels following treatment with SFX-01 (300mg bid).
Time Frame
up to 14 days
Title
Serum Haptoglobin levels
Description
To determine if up to 28 days treatment with SFX-01 increases serum haptoglobin (HP) levels following SAH
Time Frame
Up to 28 days
Title
Delayed Cerebral Ischaemia
Description
To determine if up to 28 days treatment with SFX-01 can reduce the incidence of Delayed Cerebral Ischaemia (DCI) following SAH.
Time Frame
Up to 28 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients with radiological evidence of spontaneous SAH
Fisher grade 3 or 4 on CT
Definitive treatment of aneurysm has not been ruled out
Previously living independently
In the opinion of the investigator, the delay from ictus to randomisation and initiation of trial medication will not exceed 48 hours
Aged 18 to 80 years
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:
Traumatic SAH
Fisher grade 1 or 2
SAH diagnosed on lumbar puncture with no evidence of blood on CT
Decision not to treat aneurysm has been made
Plan to withdraw treatment
Significant kidney disease as defined as plasma creatinine ≥2.5mg/dL (221 µmol/l)
Liver disease as defined as total bilirubin ≥2-fold the upper limit of normal; (ULN) as measured by the local laboratory
Females who are pregnant or lactating.
Participants enrolled in another interventional research trial in the last 30 days
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Diederik Bulters, MBChB, BSc
Organizational Affiliation
University Hospital Southampton NHS Foundation Trust
Official's Role
Principal Investigator
Facility Information:
Facility Name
Southampton General Hospital
City
Southampton
State/Province
Hampshire
ZIP/Postal Code
SO16 6YD
Country
United Kingdom
Facility Name
Western General Hospital
City
Edinburgh
ZIP/Postal Code
EH4 4XU
Country
United Kingdom
Facility Name
The Royal London Hospital
City
London
ZIP/Postal Code
E1 1BB
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
32217557
Citation
Zolnourian AH, Franklin S, Galea I, Bulters DO. Study protocol for SFX-01 after subarachnoid haemorrhage (SAS): a multicentre randomised double-blinded, placebo controlled trial. BMJ Open. 2020 Mar 25;10(3):e028514. doi: 10.1136/bmjopen-2018-028514.
Results Reference
derived
Learn more about this trial
SFX-01 After Subarachnoid Haemorrhage
We'll reach out to this number within 24 hrs