Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12625000828426p
Ethics application status
Not yet submitted
Date submitted
8/07/2025
Date registered
1/08/2025
Date last updated
1/08/2025
Date data sharing statement initially provided
1/08/2025
Type of registration
Prospectively registered

Titles & IDs
Public title
Randomized ControllEd PhaSe-II Clinical TriAl of Methylene Blue veRsus Placebo in Cardiac ArresT (RESTART) Study
Scientific title
Randomized ControllEd PhaSe-II Clinical TriAl of the effect of Methylene Blue veRsus Placebo on Neurological Status in Cardiac ArresT - RESTART Study
Secondary ID [1] 314847 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cardiac arrest 338115 0
Condition category
Condition code
Cardiovascular 334409 334409 0 0
Coronary heart disease
Cardiovascular 334410 334410 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Eligible patients will be randomised in a 1:1 fashion to receive EITHER Methylene blue (MeB) or Placebo: The study medication will be administered by a registered nurse in the emergency department with the administration recorded on the electronic medical record (EMR) for hospital & study purposes

Methylene Blue (PROVEBLUE 50mg/10mL):
• 2mg/Kg of MeB will be administered over a 5-minute IV push (with the IV flushed using 10mL of normal saline, contained within an opaque syringe)
• Following administration of the bolus, an infusion will be commended at a rate of 0.25mg/kg/hour for a total of 12 hours (opaque bag)
Intervention code [1] 331450 0
Treatment: Drugs
Comparator / control treatment
Placebo:
• 20 mL of normal saline over a 5-minute IV push (contained in an opaque syringe)
• Infusion of normal saline at a rate of 50mL per hour for 12 hours (opaque bat concealing treatment allocation)
Control group
Placebo

Outcomes
Primary outcome [1] 342101 0
The difference from baseline in serum neuron specific enolase (NSE) (a biomarker of neuronal injury) concentration
Timepoint [1] 342101 0
24h, 48 h and 72h after randomisation
Primary outcome [2] 342102 0
Survival with favourable neurological outcome (cerebral performance category less than 3 at hospital discharge) at hospital discharge
Timepoint [2] 342102 0
At hospital discharge
Primary outcome [3] 342250 0
The difference from baseline in S100b protein (a biomarker of glial injury) concentration
Timepoint [3] 342250 0
24, 48 and 72 hrs after randomisation
Secondary outcome [1] 449579 0
Survival with favourable neurological outcome (cerebral performance category less than 3
Timepoint [1] 449579 0
At hospital discharge and at 6 months after randomisation
Secondary outcome [2] 450113 0
Difference in vasoactive-inotropic score (VIS)
Timepoint [2] 450113 0
Duration of hospital admission
Secondary outcome [3] 450114 0
All cause mortality
Timepoint [3] 450114 0
At hospital discharge and at 6 months after randomisation
Secondary outcome [4] 450116 0
Recurrent arrhythmia requiring intervention (i.e. chemical or direct current cardioversion)
Timepoint [4] 450116 0
24 hrs following randomisation
Secondary outcome [5] 450117 0
Institution of renal replacement therapy
Timepoint [5] 450117 0
Hospital discharge
Secondary outcome [6] 450118 0
Duration of mechanical ventilation
Timepoint [6] 450118 0
Hospital discharge
Secondary outcome [7] 450119 0
Length of ICU admission
Timepoint [7] 450119 0
Hospital discharge
Secondary outcome [8] 450120 0
Length of hospital stay
Timepoint [8] 450120 0
Hospital discharge
Secondary outcome [9] 450121 0
Institution of mechanical circulatory support following randomisation
Timepoint [9] 450121 0
Hospital discharge
Secondary outcome [10] 450122 0
Difference in metabolic status (pH)
Timepoint [10] 450122 0
24, 48 and 72 hours after randomisation
Secondary outcome [11] 450123 0
Difference in metabolic status (lactate)
Timepoint [11] 450123 0
24, 48 and 72 hours after randomisation

Eligibility
Key inclusion criteria
• Aged 18 and older
• Cardiac arrest of non-traumatic etiology
• Shockable first detected rhythm (ventricular fibrillation or ventricular tachycardia)
• Total low-flow time (estimated time from cardiac arrest to return of spontaneous circulation (ROSC)) of no greater than 30 minutes.
• Randomization within 30 minutes of initial ROSC
• Systolic blood pressure <120mmHg or receiving vasoactive medication for hemodynamic support.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Death considered imminent
• Known to be pregnant
• Known use of selective serotonin re-uptake inhibitor (SSRI)
• Known end stage renal failure
• Known glucose-6-phosphate dehydrogenase (G6PD) deficiency

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)
Opaque envelopes and containers
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computer generated code utilising block randomisation in block sizes of 6
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
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
2/02/2026
Actual
Date of last participant enrolment
Anticipated
31/12/2027
Actual
Date of last data collection
Anticipated
3/07/2028
Actual
Sample size
Target
66
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 319407 0
Government body
Name [1] 319407 0
NHMRC
Country [1] 319407 0
Australia
Funding source category [2] 319408 0
University
Name [2] 319408 0
Monash University
Country [2] 319408 0
Australia
Primary sponsor type
Hospital
Name
The Alfred Hospital
Address
Country
Australia
Secondary sponsor category [1] 321892 0
University
Name [1] 321892 0
Monash University
Address [1] 321892 0
Country [1] 321892 0
Australia

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 317979 0
Alfred Hospital Ethics Committee
Ethics committee address [1] 317979 0
Ethics committee country [1] 317979 0
Australia
Date submitted for ethics approval [1] 317979 0
30/08/2025
Approval date [1] 317979 0
Ethics approval number [1] 317979 0

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

Contacts
Principal investigator
Name 142758 0
Prof David Kaye
Address 142758 0
Department of Cardiology, The Alfred Hospital, 55 Commercial Road Melbourne VIC 3004
Country 142758 0
Australia
Phone 142758 0
+61 3 9076 3263
Fax 142758 0
Email 142758 0
[email protected]
Contact person for public queries
Name 142759 0
David Kaye
Address 142759 0
Department of Cardiology, The Alfred Hospital, 55 Commercial Road Melbourne VIC 3004
Country 142759 0
Australia
Phone 142759 0
+61 3 9076 3263
Fax 142759 0
Email 142759 0
[email protected]
Contact person for scientific queries
Name 142760 0
David Kaye
Address 142760 0
Department of Cardiology, The Alfred Hospital, 55 Commercial Road Melbourne VIC 3004
Country 142760 0
Australia
Phone 142760 0
+61 3 9076 3263
Fax 142760 0
Email 142760 0
[email protected]

Data sharing statement
Will the study consider sharing individual participant data?
No


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.