Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12608000090314
Ethics application status
Approved
Date submitted
15/02/2008
Date registered
15/02/2008
Date last updated
3/07/2012
Type of registration
Retrospectively registered

Titles & IDs
Public title
Effects of methylene blue infusion on gastrointestinal perfusion and gut mucosal damage in septic shock patients
Scientific title
The effects of methylene blue infusion on gastrointestinal perfusion and gut mucosal damage in septic shock patients
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
septic shock 2841 0
Condition category
Condition code
Cardiovascular 2974 2974 0 0
Diseases of the vasculature and circulation including the lymphatic system

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Methylene blue infusion 1 mg/kg/hr during 4 hours
Intervention code [1] 2571 0
Treatment: Drugs
Comparator / control treatment
No control group, measurements compared to baseline
Control group
Uncontrolled

Outcomes
Primary outcome [1] 3850 0
Tonometry: decrease in difference between gastric and arterial CO2 (Carbon Dioxide) partial pressure (Pg-aCO2 gradient) of more than 5 mmHg
Timepoint [1] 3850 0
Measured at baseline and every 30 minutes for 6 hours
Secondary outcome [1] 6485 0
Urinary level of intestinal fatty acid binding protein (iFABP)
Timepoint [1] 6485 0
Measured at baseline, after 6 and after 24 hours

Eligibility
Key inclusion criteria
Patients with refractory septic shock defined as having a mean arterial pressure < 70 mmHg despite norepinephrine infusion > 0.2 mcg/kg/min
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
myocardial infarction < 6 months prior to study, pregnancy

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/11/2004
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
10
Accrual to date
Final
Recruitment outside Australia
Country [1] 797 0
Netherlands
State/province [1] 797 0

Funding & Sponsors
Funding source category [1] 3093 0
Self funded/Unfunded
Name [1] 3093 0
Country [1] 3093 0
Netherlands
Primary sponsor type
Individual
Name
Dr Frank van Haren
Address
Department of Intensive Care Waikato Hospital Private Bag 3200 Hamilton
Country
New Zealand
Secondary sponsor category [1] 2784 0
Individual
Name [1] 2784 0
Dr Peter Pickkers
Address [1] 2784 0
Intensive Care Department
Radboud University Nijmegen Medical Centre
Nijmegen
Country [1] 2784 0
Netherlands

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 5041 0
Central Committee on Research Involving Humans in the Netherlands (CCMO)
Ethics committee address [1] 5041 0
Postbus 16302
2500 BH Den Haag
The Netherlands
www.ccmo.nl
Ethics committee country [1] 5041 0
Netherlands
Date submitted for ethics approval [1] 5041 0
Approval date [1] 5041 0
17/08/2004
Ethics approval number [1] 5041 0
P04.0589C

Summary
Brief summary
Patients with severe sepsis (infection) frequently die. Sepsis interferes with the clotting and inflammatory systems and affects the heart, blood pressure as well as tissue oxygenation of the body. The pathogenesis of vasodilation and organ dysfunction in septic shock involves the excessive production of nitric oxide (NO) by activated inducible NO synthase (iNOS). NO stimulates the soluble intracellular enzyme guanylate cyclase (sGC), increasing the generation of cyclic guanosine monophosphate (cGMP). Ultimately, this pathway leads to vasodilation, myocardial depression, increased vascular permeability, loss of gut barrier function, and organ dysfunction. Methylene blue (MB) is a chemical dye that has been shown to scavenge NO, inhibit iNOS, and to inhibit sGC. In septic patients, small trials of MB have consistently demonstrated an increase in blood pressure. MB has been shown to be safe in humans, and has been used for treatment of cyanide poisoning, methemoglobimemia, and malaria. In this study we administered MB to 10 Intensive Care patients with septic shock. A variety of invasive and non-invasive measurements and blood tests were taken over a 24 hour period. Demographic data and illness severity scores were recorded as well as usual haemodynamic measures and recordings for seriously ill patients.
Statistical analysis using standard techniques, was done on SPSS version 14.0.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 28379 0
Address 28379 0
Country 28379 0
Phone 28379 0
Fax 28379 0
Email 28379 0
Contact person for public queries
Name 11536 0
Dr Frank van Haren
Address 11536 0
Department of Intensive Care Waikato Hospital Private Bag 3200 Hamilton
Country 11536 0
New Zealand
Phone 11536 0
+64 78398899
Fax 11536 0
+64 78398912
Email 11536 0
[email protected]
Contact person for scientific queries
Name 2464 0
Dr Frank van Haren
Address 2464 0
Department of Intensive Care Waikato Hospital Private Bag 3200 Hamilton
Country 2464 0
New Zealand
Phone 2464 0
+64 78398899
Fax 2464 0
+64 78398912
Email 2464 0
[email protected]

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
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