Trial Review

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12613001191785
Ethics application status
Approved
Date submitted
28/10/2013
Date registered
30/10/2013
Date last updated
19/01/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
A Pilot, Randomised, Blinded, Feasibility, Safety and Biochemical and Physiological Efficacy Study of Terlipressin versus Placebo in Hypotensive Sepsis
Scientific title
A Pilot, Randomised, Blinded, Feasibility, Safety and Biochemical and Physiological Efficacy Study of Terlipressin versus Placebo in Hypotensive Sepsis
Secondary ID [1] 283468 0
Nil
Universal Trial Number (UTN)
Trial acronym
Sepsis STEP
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hospitalised patients with sepsis-associated hypotension 290382 0
Condition category
Condition code
Infection 290773 290773 0 0
Other infectious diseases
Cardiovascular 290774 290774 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The study will recruit patients in the Emergency Department (ED), in the Intensive care unit (ICU) and in the wards after a Medical Emergency Team (MET) review. Eligible patients will be randomised to receive either:
- Terlipressin at 0.85 mg 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.

The initial treatment dose will be 0.425 mg (half dose). If haemodynamic goals are achieved after one hour the participant will only receive the study drug at half dose. However, if the haemodynamic goals are not met after one hour the remaining half dose will be administered and the participant will receive the full-dose (0.85 mg) of the study drug.

In all instances treatment will be given every six hours until resolution of hypotension or to a maximum of 24 hours using the individualised patient-responsive dose.
Intervention code [1] 288177 0
Treatment: Drugs
Comparator / control treatment
Normal saline 0.9% (as placebo)
Control group
Placebo

Outcomes
Primary outcome [1] 290772 0
Mean arterial blood pressure via continuous invasive monitoring (arterial line)
Timepoint [1] 290772 0
one hour after intravenous drug administration
Secondary outcome [1] 305248 0
The amount of intravenous fluid given in the first hour after after intravenous drug administration as per fluid balance chart
Timepoint [1] 305248 0
In the first hour after intravenous drug administration
Secondary outcome [2] 305249 0
The amount of intravenous fluid given in the 6 hours after intravenous drug administration as per fluid balance chart
Timepoint [2] 305249 0
in the first 6 hours after intravenous drug administration
Secondary outcome [3] 305250 0
The amount of intravenous fluid given in the 24 hours after intravenous drug administration as per fluid balance chart
Timepoint [3] 305250 0
in the first 24 hours after intravenous drug administration
Secondary outcome [4] 305251 0
Blood creatinine levels as per hospital pathology analysis
Timepoint [4] 305251 0
assessed daily in the first 3 days after randomisation
Secondary outcome [5] 305252 0
Incidence of acute kidney injury based on creatinine according to risk, injury, failure, loss, end-stage (RIFLE) classification as per changes in blood creatinine levels as per hospital pathology level
Timepoint [5] 305252 0
assessed daily in the first 3 days after randomisation
Secondary outcome [6] 305987 0
The amount of vasopressor drug given in the first hour after intravenous drug administration as per fluid balance chart
Timepoint [6] 305987 0
In the first hour after intravenous drug administration
Secondary outcome [7] 305988 0
The amount of vasopressor drug given in the 6 hours after intravenous drug administration as per fluid balance chart
Timepoint [7] 305988 0
In the first 6 hours after intravenous drug administration
Secondary outcome [8] 305989 0
The amount of vasopressor drug given in the24 hours after intravenous drug administration as per fluid balance chart
Timepoint [8] 305989 0
In the first 24 hours after intravenous drug administration

Eligibility
Key inclusion criteria
- Patients aged 18 years or older
- Confirmed or suspected sepsis
presentation to the emergency department (ED) or activation of an urgent medical emergency team review or admission to the intensive care unit
Hypotension
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Pregnancy
- Death is considered imminent (within 24 hours)
- Known contraindications to terlipressin such as: severe peripheral vascular disease, Raynaud's phenomenon, Known allergy to terlipressin, Unstable angina, Recent myocardial infarction, Asthma.

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)
The study will recruit such patients in the Emergency Department (ED), in the ICU and in the wards after a Medical Emergency Team review. Eligible patients will be randomised to receive either:
- Terlipressin at 0.85 mg 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.

The initial treatment dose will be 0.425 mg (half dose). If haemodynamic goals are achieved after one hour the participant will only receive the study drug at half dose. However, if the haemodynamic goals are not met after one hour the remaining half dose will be administered and the participant will receive the full-dose (0.85 mg) of the study drug.

In all instances treatment will be given every six hours until resolution of hypotension or to a maximum of 24 hours using the individualised patient-responsive dose.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomization 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.

Using data from previous studies, we estimate that a sample size of 18 patients in each group, will have a >90% statistical power at an alpha of 0.05, to detect a clinically significant increase in mean arterial pressure of 10 mmHg to 70 mmHg at one hour after injection assuming a standard deviation of 10 mmHg.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/03/2014
Actual
25/08/2014
Date of last participant enrolment
Anticipated
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] 1618 0
Austin Health - Austin Hospital - Heidelberg
Recruitment postcode(s) [1] 7500 0
3084 - Banyule

Funding & Sponsors
Funding source category [1] 288175 0
Hospital
Name [1] 288175 0
Anaesthesia Intensive Care Trust Fund
Country [1] 288175 0
Australia
Primary sponsor type
Hospital
Name
Anaesthesia Intensive Care Trust Fund
Address
c/o Department of Intensive Care
Austin Hospital
145 Studley Road
Heidelberg, VIC, 3084
Country
Australia
Secondary sponsor category [1] 286898 0
None
Name [1] 286898 0
Address [1] 286898 0
Country [1] 286898 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 290088 0
Austin Health Human Research Ethics Committee
Ethics committee address [1] 290088 0
Office for Research
Austin Hospital
145 Studley Road
Heidelberg VIC 3084
Ethics committee country [1] 290088 0
Australia
Date submitted for ethics approval [1] 290088 0
19/11/2013
Approval date [1] 290088 0
28/03/2014
Ethics approval number [1] 290088 0

Summary
Brief summary
The management of patients who have serious infection and a low blood pressure is complex and includes making sure that the circulation is stable, safe and optimal in terms of blood flow to vital organs. This is called resuscitation. The best way to deliver resuscitation is uncertain. However, it typically includes the use of fluids given though a vein and drugs to help increase blood pressure.

Drugs to increase blood pressure can be useful but those available either have a short duration of action (minutes) or can only be given though a large vein. As the need for drugs to increase blood pressure can last for hours or even days, this means that a special catheter needs to be inserted for such treatment into a large central vein like the jugular (neck) vein. This carries risks, requires special expertise and takes time. Thus, potentially helpful treatment is often delayed. As a consequence, blood pressure may remain undesirably low for more than an hour and/or the patient may be given large amounts of fluids instead, which can be undesirable. More recently, however, a medication called terlipressin has been developed to help liver patients with low blood pressure and worsening kidney function. Terlipressin can be given as a single dose injection 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 serious infection. 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 patients with infection. In this study we aim to test whether, in patients with infection and low blood pressure, terlipressin is more effective than placebo (dummy injection) at restoring blood pressure and whether such treatment changes the amount of fluid given and kidney function.
Trial website
Trial related presentations / publications
Public notes
Attachments [1] 317 317 0 0
/AnzctrAttachments/365210-HREC13Austin258(Prot and PICF's)OOS - Amendment Single Site - ethics & ....pdf

Contacts
Principal investigator
Name 43898 0
Prof Rinaldo Bellomo
Address 43898 0
Department of Intensive Care
Austin Hospital
145 Studley Road
Heidelberg VIC 3084
Country 43898 0
Australia
Phone 43898 0
+61 3 9494 5992
Fax 43898 0
+61 3 9496 3932
Email 43898 0
[email protected]
Contact person for public queries
Name 43899 0
Prof Rinaldo Bellomo
Address 43899 0
Department of Intensive Care
Austin Hospital
145 Studley Road
Heidelberg VIC 3084
Country 43899 0
Australia
Phone 43899 0
+61 3 9496 5992
Fax 43899 0
+61 3 9496 3932
Email 43899 0
[email protected]
Contact person for scientific queries
Name 43900 0
Prof Rinaldo Bellomo
Address 43900 0
Department of Intensive Care
Austin Hospital
145 Studley Road
Heidelberg VIC 3084
Country 43900 0
Australia
Phone 43900 0
+61 3 9496 5992
Fax 43900 0
+61 3 9496 3932
Email 43900 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

Current supporting documents:


Updated to:
Doc. No.TypeCitationLinkEmailOther DetailsAttachment
23295Study protocol  [email protected]

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.