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Trial registered on ANZCTR


Registration number
ACTRN12618001675213
Ethics application status
Approved
Date submitted
13/09/2018
Date registered
11/10/2018
Date last updated
11/10/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
A Pilot, Randomised Controlled Study of Ivabradine for Heart Rate Reduction in Critically Ill Patients with Septic Shock
Scientific title
A Pilot, Randomised Controlled Study to evaluate whether the administration of enteral Ivabradine plus standard care reduces tachycardia in critically ill adult patients with septic shock compared to standard care alone.
Secondary ID [1] 296078 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Tachycardia 309646 0
Critical illness 309648 0
Septic shock 309868 0
Condition category
Condition code
Cardiovascular 308449 308449 0 0
Other cardiovascular diseases
Infection 308599 308599 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Enteral ivabradine 5mg twice daily in addition to standard care.
Study treatment will be given for a total of 120 hours (5 days) or until the patient is discharged from ICU (whichever occurs first). In the event of bradycardia with a HR of <50 or in the presence of symptomatic bradycardia or in the event of AF or any visual disturbance, Ivabra-dine will be discontinued. These data will be included in the final manuscript of the study.
Intervention code [1] 312416 0
Treatment: Drugs
Comparator / control treatment
Standard care will be as per surviving sepsis campaign which include initial resuscitation without fluids, screening for sepsis, diagnostic tools, adequate antimicrobial treatment, source control, hemodynamic support with fluids, vasopressors, inotropic therapy ± corticosteroids and other supportive therapy or as per physician discretion.
Control group
Active

Outcomes
Primary outcome [1] 307434 0
Proportion of participants with a change in heart rate of less than 20 beats per minute compared to the heart rate before the start of Ivabradine. This outcome will be assessed utilising ongoing cardiac monitoring.
Timepoint [1] 307434 0
4 hours post administration of first dose of Ivabradine
Secondary outcome [1] 351889 0
Cardiac output as assessed by minimally invasive cardiac output monitoring device such as Vigilo or Flotrac.
Timepoint [1] 351889 0
every hour post administration of every dose of Ivabradine for total of 6 hours
Secondary outcome [2] 352439 0
blood pressure monitoring.All patients will have automated sphygmomanometer.
Timepoint [2] 352439 0
every hour post administration of every dose of Ivabradine for total of 6 hours

Eligibility
Key inclusion criteria
• Patients aged equal and/or older than18 years
• Septic shock as defined as
o Hypotension (mean arterial pressure < 65 mmHg) not respon-sive to fluid resuscitation
o Requirements for vasopressors (noradrenaline, vasopressin, metaraminol, phenylephrine)
o Infection of any source
• Sinus tachycardia with heart rate equal or greater than 100
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria
• Acute heart failure as defined by the presence of cardiogenic shock or cardiogenic pulmonary edema
• Arrhythmmias include Atrial fibrillation (AF)
• Acute hepatic failure as defined by the development of severe acute liver injury with encephalopathy and impaired synthetic function (INR equal or greater than 1.5) in a patient with no pre-existing liver disease
• Decompensated chronic liver disease as defined by the presence of jaundice, ascites, variceal haemorrhage or hepatic encephalopathy in a patient with known liver cirrhosis
• Physician preference
• If the patient expected to die during this admission
• Pregnancy

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)
sequentially numbered sealed envelopes
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation will be by means of sequentially numbered sealed envelopes utilising permuted blocks of variable size. Each envelope will contain a study arm allocation.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
This is a pilot randomised controlled trial comparing the use of ivabradine plus standard care compared to standard care alone in the management of septic shock without multi-organ failure.
Phase
Phase 3
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Comparisons will be made using t-test and ANOVA for repeated-measures or Wilcoxon rank-signed test and Kruskall-Wallis according to the underly-ing distribution for continuous data and Chi-square for categorical data. Logistic regression analysis will also be performed to adjust for baseline im-balances. Analysis will be on an intention-to-treat basis.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
30/11/2018
Actual
Date of last participant enrolment
Anticipated
3/06/2019
Actual
Date of last data collection
Anticipated
9/06/2019
Actual
Sample size
Target
20
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 11855 0
Monash Medical Centre - Clayton campus - Clayton
Recruitment postcode(s) [1] 23993 0
3168 - Clayton

Funding & Sponsors
Funding source category [1] 300670 0
Other
Name [1] 300670 0
Monash health pharamcy department
Country [1] 300670 0
Australia
Primary sponsor type
Other Collaborative groups
Name
Perioperative and Critical Care Research Monash Medical Centre
Address
246 Clayton Rd,
Clayton VIC
3168
Country
Australia
Secondary sponsor category [1] 300192 0
None
Name [1] 300192 0
NA
Address [1] 300192 0
NA
Country [1] 300192 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 301451 0
The Monash Health Human Research Ethics Committee (HREC)
Ethics committee address [1] 301451 0
246 Clayton Road, Clayton, Victoria 3168
Ethics committee country [1] 301451 0
Australia
Date submitted for ethics approval [1] 301451 0
05/07/2018
Approval date [1] 301451 0
11/07/2018
Ethics approval number [1] 301451 0

Summary
Brief summary
Septic shock is a state of low blood pressure resulting from a physiological response to an infection. The low blood pressure commonly presents along with an elevated heart rate, which is in turn associated with poor outcomes in patients. Beta blockers have had favourable effects in the past, but its use in this clinical context may potentially lead to an exacerbation of the low blood pressure.
Ivabradine causes selective heart rate reduction via an alternative pathway and is not known to have any other effects on the heart. It has previously been shown to have benefit in the treatment of chronic heart failure and stable cardiac disease, and previous studies have documented safety and tolerability. Furthermore, it has been used in acute medicine for the treat-ment of patients with low blood pressure due to acute heart failure and is currently being tested in critically ill patients with multi-organ failure.
We propose to conduct a feasibility study to test whether Ivabradine can be used safely to reduce the heart rate in patients who are in septic shock with an elevated heart rate.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 87050 0
Dr Dr. Wisam Al-Bassam
Address 87050 0
ICU consultant
Monash Medical Centre
246 Clayton Road, Clayton, Victoria 3168
Country 87050 0
Australia
Phone 87050 0
+61 (03) 95943296
Fax 87050 0
Email 87050 0
[email protected]
Contact person for public queries
Name 87051 0
Fareda Fazli
Address 87051 0
ICU Research Coordinator
Monash Medical Centre
246 Clayton Road, Clayton, Victoria 3168
Country 87051 0
Australia
Phone 87051 0
+61 (03) 95943296
Fax 87051 0
Email 87051 0
[email protected]
Contact person for scientific queries
Name 87052 0
Dr. Wisam Al-Bassam
Address 87052 0
ICU consultant
Monash Medical Centre
246 Clayton Road, Clayton, Victoria 3168
Country 87052 0
Australia
Phone 87052 0
+61 (03) 95943296
Fax 87052 0
Email 87052 0
[email protected]

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What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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