Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12623001276640
Ethics application status
Approved
Date submitted
9/11/2023
Date registered
7/12/2023
Date last updated
23/02/2024
Date data sharing statement initially provided
7/12/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
A Pilot, Safety, Efficacy and Feasibility Double-Blind Randomised Controlled Trial of Scp776 for Neuroprotection in Comatose Adults Resuscitated After Out-of-Hospital Cardiac Arrest
Scientific title
A Pilot, Safety, Efficacy and Feasibility Double-Blind Randomised Controlled Trial of Scp776 for Neuroprotection in Comatose Adults Resuscitated After Out-of-Hospital Cardiac Arrest
Secondary ID [1] 310925 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cardiac Arrest 331987 0
Condition category
Condition code
Cardiovascular 328729 328729 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Eligible patient's will be enrolled as soon as possible after admission to hospital and within 240 minutes of return of spontaneous circulation. A registered nurse or medical doctor delegated by the site principal investigator will administer to two intravenous doses of scp776 100 mg while the participant is admitted to hospital. The first dose of scp776 must be administered within 1 hour of randomisation. The second dose of study drug should be administered at approximately the same time the following day (24 h plus or minus 30 minutes from first dose). A review of medical records will confirm the date and time of study drug administration.
Intervention code [1] 327354 0
Treatment: Drugs
Comparator / control treatment
Eligible patient's will be enrolled as soon as possible after admission to hospital and within 240 minutes of return of spontaneous circulation. A registered nurse or medical doctor delegated by the site principal investigator will administer to two intravenous doses of 10 ml normal saline 0.9% (placebo) while admitted to hospital. The first dose of normal saline 0.9% must be administered within 1 hour of randomisation. The second dose of study drug should be administered at approximately the same time the following day (24 h plus or minus 30 minutes from first dose). A review of medical records will confirm the date and time of study drug administration.
Control group
Placebo

Outcomes
Primary outcome [1] 336539 0
Volume of brain injury between the scp776 group and the placebo group as calculated by automated assessment of brain magnetic resonance imaging.
Timepoint [1] 336539 0
Brain magnetic resonance imaging is to be performed between 72 – 96 hours following randomisation and data extracted from the patients electronic medical record.
Secondary outcome [1] 428732 0
Serial serum neurofilament light chain concentrations between the scp776 group and the placebo group.
Timepoint [1] 428732 0
Serum blood samples to be obtained at baseline, 24 hours, 48 hours and 72 hours in patients admitted to hospital.
Secondary outcome [2] 428733 0
Degree of functional outcome, defined as a score of 4 to 6 using the 6-point modified Rankin scale
Timepoint [2] 428733 0
Assessed at 30-days and six months after randomisation.
Secondary outcome [3] 428734 0
Degree of neurological outcome, defined as a score of 5 or greater using the 8-point Glasgow Outcome Scale Extended method
Timepoint [3] 428734 0
As assessed at six months after randomisation
Secondary outcome [4] 428735 0
Health-related quality of life
Timepoint [4] 428735 0
As assessed at six months after randomisation
Secondary outcome [5] 428736 0
Adverse event
Timepoint [5] 428736 0
As recorded in the participant electronic medical record occurring in the first seven days from randomisation.
Secondary outcome [6] 428737 0
Study drug administration
Timepoint [6] 428737 0
As recorded in the participant electronic medical record occurring in the first 48 hours of the participant's admission to hospital.

Eligibility
Key inclusion criteria
Adult age equal to or greater than 18 years of age
Out-of-hospital cardiac arrest of a presumed cardiac or unknown cause
Sustained return of spontaneous circulation defined as 20 minutes with signs of circulation without the need for chest compressions.
Unconscious defined as a FOUR-score motor response of less than 4 which is not able to obey verbal commands after sustained return of spontaneous circulation
Eligible for intensive care without restrictions or limitations
Within 240 minutes of return of spontaneous circulation
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Unwitnessed cardiac arrest with an initial rhythm of asystole
Temperature on admission less than 30 degrees Celsius
On extracorporeal membrane oxygenation prior to return of spontaneous circulation
Obvious or suspected pregnancy
Severe hypoglycemia defined as a serum glucose level of less than 60 mg per deciliter
Patients receiving more than 0.5 mcg per kilogram per minute of norepinephrine equivalent
Patient with severe active haemorrhage
Known or suspected metal implants that would preclude the ability to tolerate a magnetic resonance imaging scan.
Patients residing in a nursing home.
Patients having a reported weight of less than 50 kilograms
Previously enrolled into the PROSPER trial

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
central randomisation by computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Permuted block randomisation
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
The efficacy and safety of the intervention will be evaluated using an intention-to-treat analysis for evaluable patients (those able to receive an MRI scan). Recruitment of participants will be targeted to achieve a sample size of 40 evaluable patients with automated MR imaging between 72 – 96 hours. This sample size is deemed sufficient to allow for a meaningful assessment of neurological assessment biological efficacy differences between groups and to evaluate the additional efficacy outcomes, along with those of safety and feasibility outcomes.

We anticipate that some patients treated with the trial drug may die before their scheduled MRI brain scan can be performed. Thus, such losses will introduce competing risk bias in the assessment of the main effect (the ADC). To address this bias, we will apply sensitivity analyses. First, we will allocate the lowest record ADC to all patients who died before receiving an MRI. Second, in an additional sensitivity analysis we will allocate the median ADC from each group to those patients from that group who did not survive to MRI scanning. Third, we will use competing risk analysis which adjusts for baseline characteristics in assessing outcomes in evaluable patients.

Continuous data is reported as median with interquartile range and compared using Mann–Whitney U test. Categorical data are reported as number and percentage and compared using Chi-square or Fisher exact test where indicated. The change in biomarker concentrations over time will be assessed using repeated measurements analysis of variance (ANOVA). To compare the change over time between the two groups (scp776 and placebo), an interaction variable between group and time will be included in the ANOVA model. A two-sided p-value of 0.05 will be used to indicate statistical significance. We plan to use the R statistical package to perform all analyses.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/04/2024
Actual
Date of last participant enrolment
Anticipated
31/03/2026
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
40
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 25824 0
Austin Health - Austin Hospital - Heidelberg
Recruitment postcode(s) [1] 41651 0
3084 - Heidelberg

Funding & Sponsors
Funding source category [1] 315186 0
Commercial sector/Industry
Name [1] 315186 0
Silver Creek Pharmaceuticals
Country [1] 315186 0
United States of America
Primary sponsor type
Hospital
Name
Austin Hospital
Address
145 Studley Road Heidelberg VIC 3084
Country
Australia
Secondary sponsor category [1] 317212 0
None
Name [1] 317212 0
Address [1] 317212 0
Country [1] 317212 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 314117 0
Austin Health Human Research Ethics Committee
Ethics committee address [1] 314117 0
Ethics committee country [1] 314117 0
Australia
Date submitted for ethics approval [1] 314117 0
09/11/2023
Approval date [1] 314117 0
08/02/2024
Ethics approval number [1] 314117 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 130466 0
Prof Rinaldo Bellomo
Address 130466 0
Department of Intensive Care, Austin Hospital, 145 Studley Road, Heidelberg, Victoria, Australia 3084
Country 130466 0
Australia
Phone 130466 0
+61394965992
Fax 130466 0
+61394963932
Email 130466 0
[email protected]
Contact person for public queries
Name 130467 0
Rinaldo Bellomo
Address 130467 0
Department of Intensive Care, Austin Hospital, 145 Studley Road, Heidelberg, Victoria, Australia 3084
Country 130467 0
Australia
Phone 130467 0
+61 394965992
Fax 130467 0
+61394963932
Email 130467 0
[email protected]
Contact person for scientific queries
Name 130468 0
Rinaldo Bellomo
Address 130468 0
Department of Intensive Care, Austin Hospital, 145 Studley Road, Heidelberg, Victoria, Australia 3084
Country 130468 0
Australia
Phone 130468 0
+61394965992
Fax 130468 0
+61394963932
Email 130468 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
No - IPD will not be available as this is a pilot, safety and feasibility trial of which the results are deemed hypothesis generating.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.