ANZCTR - Registration

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Trial registered on ANZCTR

Registration number

ACTRN12607000393459

Ethics application status

Approved

Date submitted

20/07/2007

Date registered

31/07/2007

Date last updated

31/07/2007

Type of registration

Prospectively registered

Titles & IDs

Public title

The influence of Statins on Blood Vessel Function in Severe Sepsis

Scientific title

A randomised, placebo-controlled study of the effect of atorvastatin on endothelial function in intensive care patients with severe sepsis.

Universal Trial Number (UTN)

Trial acronym

STREAMS

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Severe sepsis

Endothelial dysfunction

Condition category

Condition code

Blood

Other blood disorders

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Randomised allocation to atorvastatin 20mg capsules given orally or enterally once a day for up to 14 days.

Intervention code [1]

Treatment: Drugs

Comparator / control treatment

Identical placebo

Control group

Placebo

Outcomes

Primary outcome [1]

Change in endothelial function (as measured by peripheral arterial tonometry).

Timepoint [1]

At 24 and 48 hours following randomisation.

Secondary outcome [1]

1) Intensive Care Unit (ICU), hospital and 28 day mortality

Timepoint [1]

Secondary outcome [2]

2) Change in microvascular function as measured by near-infrared spectroscopy

Timepoint [2]

Over the first 24 and 48 hours.

Secondary outcome [3]

3) Severity of organ dysfunction (as measured by Sequential Organ Function Assessment (SOFA) scores)

Timepoint [3]

Over the first 7 days

Secondary outcome [4]

4) Change in plasma arginine:ADMA (Asymmetric DiMethyl Arginine) ratio

Timepoint [4]

Over the first 7 days

Secondary outcome [5]

5) Change in serum markers of endothelial activation

Timepoint [5]

Over the first 7 days

Secondary outcome [6]

6) Safety of atorvastatin in severe sepsis as measured by frequency of adverse events throughout the study.

Timepoint [6]

Eligibility

Key inclusion criteria

1) Admitted to the Intensive Care Unit 2) Severe sepsis for less than 24 hours. Severe sepsis is defined as strongly suspected or proven infection, 3 or more SIRS criteria and at least one acute organ dysfunction attributable to the sepsis.

Minimum age

18 Years

Maximum age

90 Years

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

1) Pregnancy or breastfeeding2) Death is imminent3) History of intolerance to a statin4) Acute liver failure5) Child's C cirrhosis6) ALT>5x upper limit of normal7) CK > 5x upper limit of normal8) Patient unable to take oral or enteral medication9) Patient or next of kin not able to provide informed consent10) Patient, family or treating doctor not in favour of aggressive treatment11) Coagulopathy (INR>2.0 OR APTT>70)12) Severe thrombocytopaenia (Platelets<20)13) Latex allergy.

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)

Central randomisation by telephone.

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Computerised sequence generation, in permuted blocks, stratified by previous statin use

Masking / blinding

Blinded (masking used)

Who is / are masked / blinded?

Intervention assignment

Parallel

Other design features

Blinding will apply to the study subjects, the doctors and nurses in the intensive care unit (who will be administering the treatment), the study investigators (who will be enrolling patients and performing measurements), and the chief investigator (who will be analysing the data). That is, the subjects, clinicians, assessors and data analyst will all be blinded as to the treatment assignment.

Phase

Phase 2

Type of endpoint/s

Safety/efficacy

Statistical methods / analysis

Recruitment

Recruitment status

Not yet recruiting

Date of first participant enrolment

Anticipated

7/08/2007

Actual

Date of last participant enrolment

Anticipated

Actual

Date of last data collection

Anticipated

Actual

Sample size

Target

Accrual to date

Final

Funding & Sponsors

Funding source category [1]

Government body

Name [1]

National Health and Medical Research Council

Address [1]

Country [1]

Australia

Primary sponsor type

Individual

Name

Dr Josh Davis

Address

Country

Secondary sponsor category [1]

Individual

Name [1]

Dr Dianne Stephens

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Royal Darwin Hospital

Ethics committee address [1]

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

Approval date [1]

17/07/2007

Ethics approval number [1]

07/34

Summary

Brief summary

15,000 people are admitted to an Intensive Care Unit in Australia with severe sepsis every year. One third of these will die. Severe sepsis occurs when an infection affects the whole body and causes dysfunction of one or more of the major organs. A significant factor in this illness is that the body's normal response to infection or 'inflammatory response' becomes abnormal. It is not completely understood why the major organs can fail in severe sepsis. Organ failure is thought to be partly due to dysfunction of the small blood vessels that supply oxygen and nutrients to organs and tissues. We have previously shown that small blood vessel function is acutely impaired in patients with severe sepsis.

The statins are a class of medications commonly used to lower cholesterol. Previous research in patients without sepsis suggests that they also have a beneficial effect on inflammation and on the function of small blood vessels. A clinical trial of atorvastatin in severe sepsis commenced in Australia and New Zealand in July 2007(The STATInS trial). The STATInS trial will be evaluating the safety of atorvastatin in severe sepsis and also its effect on inflammation and outcome. 

We propose to enroll a subset of patients from the STATInS trial into our study which will assess the effect of atorvastatin on the function of small blood vessels. 40-60% of our target recruitment will occur after the conclusion of the STATInS study, in a single-centre stand alone continuation of the study. This study will add valuable information to the STATInS trial, to help us answer questions about how and why atorvastatin helps patients with severe sepsis.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Address

Country

Phone

Fax

Contact person for public queries

Name

Dr Josh Davis

Address

Menzies School of Health Research
John Matthews Building
Royal Darwin Hospital Campus
Rocklands Drive Tiwi
Casuarina NT 0811

Country

Australia

Phone

(08) 89 228836

Fax

Joshua.Davis@menzies.edu.au

Contact person for scientific queries

Name

Dr Josh Davis

Address

Menzies School of Health Research
John Matthews Building
Royal Darwin Hospital Campus
Rocklands Drive Tiwi
Casuarina NT 0811

Country

Australia

Phone

(08) 89 228836

Fax

Joshua.Davis@menzies.edu.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

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

Source	Title	Year of Publication	DOI
Dimensions AI	To JUPITER and beyond: Statins, inflammation, and primary prevention	2010	https://doi.org/10.1186/cc9006

N.B. These documents automatically identified may not have been verified by the study sponsor.

Trial Review

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Documents added manually

Documents added automatically