ANZCTR - Registration

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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]

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

Condition category

Condition code

Infection

Other infectious diseases

Cardiovascular

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]

Treatment: Drugs

Comparator / control treatment

Normal saline 0.9% (as placebo)

Control group

Placebo

Outcomes

Primary outcome [1]

Mean arterial blood pressure via continuous invasive monitoring (arterial line)

Timepoint [1]

one hour after intravenous drug administration

Secondary outcome [1]

The amount of intravenous fluid given in the first hour after after intravenous drug administration as per fluid balance chart

Timepoint [1]

In the first hour after intravenous drug administration

Secondary outcome [2]

The amount of intravenous fluid given in the 6 hours after intravenous drug administration as per fluid balance chart

Timepoint [2]

in the first 6 hours after intravenous drug administration

Secondary outcome [3]

The amount of intravenous fluid given in the 24 hours after intravenous drug administration as per fluid balance chart

Timepoint [3]

in the first 24 hours after intravenous drug administration

Secondary outcome [4]

Blood creatinine levels as per hospital pathology analysis

Timepoint [4]

assessed daily in the first 3 days after randomisation

Secondary outcome [5]

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]

assessed daily in the first 3 days after randomisation

Secondary outcome [6]

The amount of vasopressor drug given in the first hour after intravenous drug administration as per fluid balance chart

Timepoint [6]

In the first hour after intravenous drug administration

Secondary outcome [7]

The amount of vasopressor drug given in the 6 hours after intravenous drug administration as per fluid balance chart

Timepoint [7]

In the first 6 hours after intravenous drug administration

Secondary outcome [8]

The amount of vasopressor drug given in the24 hours after intravenous drug administration as per fluid balance chart

Timepoint [8]

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?

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

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

VIC

Recruitment hospital [1]

Austin Health - Austin Hospital - Heidelberg

Recruitment postcode(s) [1]

3084 - Banyule

Funding & Sponsors

Funding source category [1]

Hospital

Name [1]

Anaesthesia Intensive Care Trust Fund

Address [1]

c/o Department of Intensive Care
Austin Hospital
145 Studley Road
Heidelberg, VIC, 3084

Country [1]

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]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Austin Health Human Research Ethics Committee

Ethics committee address [1]

Office for Research
Austin Hospital
145 Studley Road
Heidelberg VIC 3084

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

19/11/2013

Approval date [1]

28/03/2014

Ethics approval number [1]

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]

/AnzctrAttachments/365210-HREC13Austin258(Prot and PICF's)OOS - Amendment Single Site - ethics & ....pdf

Contacts

Principal investigator

Name

Prof Rinaldo Bellomo

Address

Department of Intensive Care
Austin Hospital
145 Studley Road
Heidelberg VIC 3084

Country

Australia

Phone

+61 3 9494 5992

Fax

+61 3 9496 3932

rinaldo.bellomo@austin.org.au

Contact person for public queries

Name

Rinaldo Bellomo

Address

Department of Intensive Care
Austin Hospital
145 Studley Road
Heidelberg VIC 3084

Country

Australia

Phone

+61 3 9496 5992

Fax

+61 3 9496 3932

rinaldo.bellomo@austin.org.au

Contact person for scientific queries

Name

Rinaldo Bellomo

Address

Department of Intensive Care
Austin Hospital
145 Studley Road
Heidelberg VIC 3084

Country

Australia

Phone

+61 3 9496 5992

Fax

+61 3 9496 3932

rinaldo.bellomo@austin.org.au

No information has been provided regarding IPD availability

What supporting documents are/will be available?

No Supporting Document Provided

Results publications and other study-related documents

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No additional documents have been identified.

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