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Trial registered on ANZCTR


Registration number
ACTRN12613001194752
Ethics application status
Approved
Date submitted
28/10/2013
Date registered
30/10/2013
Date last updated
18/12/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
A Pilot, Randomised, Blinded, Feasibility, Safety and Biochemical and Physiological Efficacy Study of Terlipressin vs. Placebo in Cardiac Surgery Patients with the Post-operative High Cardiac Output and Hypotension syndrome
Scientific title
A Pilot, Randomised, Blinded, Feasibility, Safety and Biochemical and Physiological Efficacy Study of Terlipressin vs. Placebo in Cardiac Surgery Patients with the Post-operative High Cardiac Output and Hypotension syndrome
Secondary ID [1] 283469 0
Nil
Universal Trial Number (UTN)
Trial acronym
STEP
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Post-operative high cardiac output and hypotension syndrome in patients following cardiac surgery 290383 0
Condition category
Condition code
Surgery 290775 290775 0 0
Other surgery
Cardiovascular 290794 290794 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Intravenous push of Terlipressin (Lucassin) 0.85mg, at baseline as a minimum and then 6 hourly for a maximum of 24 hours with the need for further doses determined by continuous invasive monitoring via an arterial line.
Intervention code [1] 288178 0
Treatment: Drugs
Comparator / control treatment
Normal Saline (0.9%)
Control group
Placebo

Outcomes
Primary outcome [1] 290773 0
Mean arterial blood pressure via continuous invasive monitoring via arterial line
Timepoint [1] 290773 0
one hour after each intravenous drug administration
Secondary outcome [1] 305253 0
Cardiac output via invasive thermodilution monitoring
Timepoint [1] 305253 0
one hour after each intravenous drug administration
Secondary outcome [2] 305254 0
Central venous pressure via invasive central venous catheter
Timepoint [2] 305254 0
one hour after each intravenous drug administration
Secondary outcome [3] 305255 0
Pulmonary artery pressure via invasive pulmonary artery catheter
Timepoint [3] 305255 0
one hour after each intravenous drug administration
Secondary outcome [4] 305256 0
Intravenous fluid given as per fluid balance chart
Timepoint [4] 305256 0
one hour after each intravenous drug administration
Secondary outcome [5] 305257 0
Intravenous fluid given as per fluid balance chart
Timepoint [5] 305257 0
In the first 6 hours after intravenous drug administration
Secondary outcome [6] 305258 0
Intravenous fluid given as per fluid balance chart
Timepoint [6] 305258 0
In the first 24 hours after intravenous drug administration
Secondary outcome [7] 305259 0
Blood creatinine levels
Timepoint [7] 305259 0
At baseline and in the first 3 days after randomisation
Secondary outcome [8] 305260 0
Incidence of acute kidney injury based on creatinine according to risk, injury, failure, loss, end-stage (RIFLE) classification
Timepoint [8] 305260 0
In the first three days after randomisation

Eligibility
Key inclusion criteria
- Patients aged 18 years or older
- Admitted to the intensive care unit after cardiopulmonary bypass
- High cardiac index (greater than 3 litres/minute/m2)
- Hypotension (systolic blood pressure less than 90 mmHg or mean arterial blood pressure less than 65 mmHg)
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Pregnancty
- Death is considered imminent (within 24 hours)
- Known sever peripheral vascular disease
- Raynaud's phenomenon
- Known allergy to terlipressin
- Unstable angina
- Recent myocardial infarction
- Asthma
- Surgery for coronary artery disease

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)
Eligible patients will be randomised to receive either:
- Terlipressin at 0.85mg IV push, OR
- Placebo (Normal Saline 0.9%)

The study treatments will be macroscopically identical and will be supplied in identical 5 ml syringes prepared by ICU research staff.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation will be by means of sealed envelopes with permuted blocks of variable size.
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 4
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
Outcomes will be compared after log transformation where appropriate. Comparisons will be made using t-test and ANOVA for repeated-measures or Wilcoxon rank-signed test and Kruskall-Wallis according to the underlying distribution for continuous data and Chi-square for categorical data. A Kaplan-Meier curve with log-rank test will be performed to further compare in-hospital mortality and rate of discharge home. Logistic regression analysis will also be performed to adjust for baseline imbalances. Analysis will be on intention-to-treat.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 1619 0
Austin Health - Austin Hospital - Heidelberg
Recruitment postcode(s) [1] 7501 0
3084 - Banyule

Funding & Sponsors
Funding source category [1] 288176 0
Hospital
Name [1] 288176 0
Anaesthesia Intensive Care Trust Fund, Austin Hospital, Austin Health
Address [1] 288176 0
c/o Department of Intensive Care
Austin Hospital
145 Studley Road
Heidelberg VIC 3084
Country [1] 288176 0
Australia
Primary sponsor type
Hospital
Name
Austin Health
Address
Austin Hospital
145 Studley Road
Heidelberg VIC 3084
Country
Australia
Secondary sponsor category [1] 286899 0
None
Name [1] 286899 0
Address [1] 286899 0
Country [1] 286899 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 290089 0
Austin Health Human Research Ethics Committee
Ethics committee address [1] 290089 0
Office for Research
Austin Hospital
145 Studley Road
Heidelberg VIC 3084
Ethics committee country [1] 290089 0
Australia
Date submitted for ethics approval [1] 290089 0
11/02/2014
Approval date [1] 290089 0
17/06/2014
Ethics approval number [1] 290089 0

Summary
Brief summary
The management of patients who have a high cardiac output (the amount of blood pumped by the heart every minute) and a low blood pressure after open heart surgery is complex because the best way to deliver best post-operative treatment of the circulation is uncertain. However, treatment typically includes the use of fluids given though a vein and drugs to help increase blood pressure to safer levels. Such blood pressure drugs can be useful but can have adverse effects on heart function or cause disturbances of the heart rhythm. Thus, they are often avoided and used very late in the management of these patients when blood pressure is really low. As a consequence, blood pressure may remain undesirably low for a long time and patients may be given large amounts of fluids instead, which can also be undesirable. More recently, however, a medication called terlipressin has been developed to help liver patients who have a high cardiac output with low blood pressure and worsening kidney function.

Terlipressin can be given as a single shot through any hand or arm vein and can increase blood pressure for up to 6 hours. Terlipressin offers the opportunity to improve blood pressure management in patients with a high cardiac output and a low blood pressure after heart surgery without the risk of causing heart injury and rhythm disturbances. However, because terlipressin has only been used to support blood pressure in this way in liver patients, we do not know how effective it would be in such selected cardiac surgery patients.

In this study we wish to test whether, in open heart surgery patients with a high cardiac output but a low blood pressure, terlipressin is more effective than placebo (dummy injection) at restoring blood pressure and whether such treatment is safe and changes the amount of fluid given and kidney function for the better.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 43902 0
Prof Rinaldo Bellomo
Address 43902 0
Department of Intensive Care
Austin Hospital
145 Studley Road
Heidelberg VIC 3084
Country 43902 0
Australia
Phone 43902 0
+61 3 9496 5992
Fax 43902 0
+61 3 9496 5992
Email 43902 0
rinaldo.bellomo@austin.org.au
Contact person for public queries
Name 43903 0
Prof Rinaldo Bellomo
Address 43903 0
Department of Intensive Care
Austin Hospital
145 Studley Road
Heidelberg VIC 3084
Country 43903 0
Australia
Phone 43903 0
+61 3 9496 5992
Fax 43903 0
+ 61 3 9496 3932
Email 43903 0
rinaldo.bellomo@austin.org.au
Contact person for scientific queries
Name 43904 0
Prof Rinaldo Bellomo
Address 43904 0
Department of Intensive Care
Austin Hospital
145 Studley Road
Heidelberg VIC 3084
Country 43904 0
Australia
Phone 43904 0
+61 3 9496 5992
Fax 43904 0
+61 3 9496 3932
Email 43904 0
rinaldo.bellomo@austin.org.au

No information has been provided regarding IPD availability
Summary results
No Results