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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 2187 0
Endothelial dysfunction 2188 0
Condition category
Condition code
Blood 2283 2283 0 0
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] 1899 0
Treatment: Drugs
Comparator / control treatment
Identical placebo
Control group
Placebo

Outcomes
Primary outcome [1] 3174 0
Change in endothelial function (as measured by peripheral arterial tonometry).
Timepoint [1] 3174 0
At 24 and 48 hours following randomisation.
Secondary outcome [1] 5291 0
1) Intensive Care Unit (ICU), hospital and 28 day mortality
Timepoint [1] 5291 0
Secondary outcome [2] 5292 0
2) Change in microvascular function as measured by near-infrared spectroscopy
Timepoint [2] 5292 0
Over the first 24 and 48 hours.
Secondary outcome [3] 5293 0
3) Severity of organ dysfunction (as measured by Sequential Organ Function Assessment (SOFA) scores)
Timepoint [3] 5293 0
Over the first 7 days
Secondary outcome [4] 5294 0
4) Change in plasma arginine:ADMA (Asymmetric DiMethyl Arginine) ratio
Timepoint [4] 5294 0
Over the first 7 days
Secondary outcome [5] 5295 0
5) Change in serum markers of endothelial activation
Timepoint [5] 5295 0
Over the first 7 days
Secondary outcome [6] 5296 0
6) Safety of atorvastatin in severe sepsis as measured by frequency of adverse events throughout the study.
Timepoint [6] 5296 0

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
Gender
Both males and females
Can healthy volunteers participate?
No
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
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] 2449 0
Government body
Name [1] 2449 0
National Health and Medical Research Council
Address [1] 2449 0
Country [1] 2449 0
Australia
Primary sponsor type
Individual
Name
Dr Josh Davis
Address
Country
Secondary sponsor category [1] 2221 0
Individual
Name [1] 2221 0
Dr Dianne Stephens
Address [1] 2221 0
Country [1] 2221 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 4303 0
Royal Darwin Hospital
Ethics committee address [1] 4303 0
Ethics committee country [1] 4303 0
Australia
Date submitted for ethics approval [1] 4303 0
Approval date [1] 4303 0
17/07/2007
Ethics approval number [1] 4303 0
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 27713 0
Address 27713 0
Country 27713 0
Phone 27713 0
Fax 27713 0
Email 27713 0
Contact person for public queries
Name 11088 0
Dr Josh Davis
Address 11088 0
Menzies School of Health Research
John Matthews Building
Royal Darwin Hospital Campus
Rocklands Drive Tiwi
Casuarina NT 0811
Country 11088 0
Australia
Phone 11088 0
(08) 89 228836
Fax 11088 0
Email 11088 0
Joshua.Davis@menzies.edu.au
Contact person for scientific queries
Name 2016 0
Dr Josh Davis
Address 2016 0
Menzies School of Health Research
John Matthews Building
Royal Darwin Hospital Campus
Rocklands Drive Tiwi
Casuarina NT 0811
Country 2016 0
Australia
Phone 2016 0
(08) 89 228836
Fax 2016 0
Email 2016 0
Joshua.Davis@menzies.edu.au

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