Contact information
Type
Scientific
Primary contact
Dr James Andrew Russell
ORCID ID
Contact details
St Paul's Hospital
Rm 240 Comox Building
1081 Burrard Street
Vancouver
V6Z 1Y6
Canada
+1 604 806 2872
jrussell@mrl.ubc.ca
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
MCT-44152
Study information
Scientific title
A randomised controlled trial of VAsopressin versus norepinephrine in Septic Shock
Acronym
VASST
Study hypothesis
To examine the effect of vasopressin versus norepinephrine in treatment of septic shock.
Ethics approval
University of British Columbia/Providence Health Care (UBC/PHC) Research Ethics Board, 17/11/1999
Study design
Randomised controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Not specified
Trial type
Treatment
Patient information sheet
Condition
Septic Shock
Intervention
Patient will be randomised in a blinded fashion to receive a continuous infusion of either vasopressin (experimental therapy) or norepinephrine (control therapy). The study infusion will be used as the primary means of stabilising and maintaining a patient's blood pressure.
Intervention type
Drug
Phase
Not Applicable
Drug names
Vasopressin, norepinephrine
Primary outcome measure
28-day survival
Secondary outcome measures
1. 90-day survival
2. Organ failure free days
3. Days alive and free of shock
4. Days alive and free of SIRS
5. Days alive and free of steroid use
6. Length of stay in the Intensive Care Units (ICU)
7. Length of stay in hospital
8. Effects on biologic markers of inflammation
9. Effect on haemodynamic variables
Overall trial start date
01/06/2001
Overall trial end date
31/01/2003
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. 776 adult patients with septic shock of either sex, 16 years and older
2. Aged greater than 16 years
3. Evidence of severe septic shock as defined by criteria listed below:
3.1. Systemic Inflammatory Response (SIRS), presence of two or more of the following:
3.1.1. Fever (temperature greater than 38°C/hypothermia less than 36°C)
3.1.2. Tachycardia (heart rate greater than 90 beats per minute)
3.1.3. Tachypnea (respiratory rate greater than 20 breaths per minute or PaCO2 32 torr or mechanically ventilated)
3.1.4. Pathologic white blood cell count (greater than 12,000 cells/mm^3, less than 4000 cells/mm^3, or greater than 10% immature band forms)
3.2. Known (culture positive) or suspected (cultures pending, patient on antibiotics) source of infection (defines sepsis)
3.3. Evidence of one new organ dysfunction (defines severe sepsis):
3.3.1. Lung (ventilated and partial pressure of oxygen in arterial blood [PaO2]/fraction of inspired oxygen [FiO2]) less than 300
3.3.2. Renal (urine output less than 30 ml/hour or less than 0.5 ml/kg body weight, for at least 1 hour)
3.3.3. Coagulation (platelet count less than 80,000/mm^3)
3.3.4. Central nervous system (CNS) (Glasgow coma scale less than 12)
3.4. Hypotension and need for vasopressors (defines severe septic shock):
3.4.1. Systolic blood pressure (SBP) less than 90 mmHg or decrease in SBP by at least 40 mmHg for more then one hour while central venous pressures remain adequate (greater than or equal to 12 mmHg) or at least 500 ml of saline was infused. Duration of hypotension may be less than one hour if vasopressors are infused to maintain blood pressure, and requirement for vasopressor support (norepinephrine equivalent) = (dopamine ÷ 2 µg/kg/min) + norepinephrine (µg/min) + epinephrine (µg/min) + phenylephrine ÷ 20 (µg/min) greater than or equal to 5 µg/min for at least six consecutive hours in the last 24 hours and on at least 5 µg/min within the last hour prior to randomisation, or severe septic shock: vasopressor support (norepinephrine equivalent, as above) greater than or equal to 15 µg/min in the last hour prior to randomisation
4. Central venous catheter (pulmonary-arterial catheter is optional)
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
776
Participant exclusion criteria
1. Physician and team are not committed to aggressive care
2. Patient who is terminal (death anticipated in 12 months)
3. Greater than 24 hours have elapsed since the patient met entry criteria
4. Patient is pregnant (pregnancy test required in all women less than 50 years)
5. Underlying chronic heart disease (New York Heart Association [NYHA] class III or IV) and shock
6. Unstable angina or myocardial infarction manifest by chest pain and S-T segment elevation within the previous 30 days
7. Acute mesenteric ischemia present or suspected
8. Severe hyponatremia (Na less than 130 mmol/l)
9. Patient has raynaud's phenomenon, systemic sclerosis or vasopastic diathesis
10. Traumatic brain injury (Glasgow Coma Score [GCS] less than 8 prior to onset of sepsis)
Recruitment start date
01/06/2001
Recruitment end date
31/01/2003
Locations
Countries of recruitment
Canada
Trial participating centre
St Paul's Hospital
Vancouver
V6Z 1Y6
Canada
Sponsor information
Organisation
University of British Columbia (Canada)
Sponsor details
2075 Wesbrook Mall
Vancouver
V6T 1Z1
Canada
+1 604 822 2454
customerservice@finance.ubc.ca
Sponsor type
University/education
Website
Funders
Funder type
Research organisation
Funder name
Canadian Institutes of Health Research (CIHR) (Canada) - http://www.cihr-irsc.gc.ca (ref: MCT-44152)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list
2008 results in: http://www.ncbi.nlm.nih.gov/pubmed/18305265
2010 results in: http://www.ncbi.nlm.nih.gov/pubmed/19841897
2010 results in: http://www.ncbi.nlm.nih.gov/pubmed/20606409
2011 resutls in: http://www.ncbi.nlm.nih.gov/pubmed/21892977
2012 results in: http://www.ncbi.nlm.nih.gov/pubmed/22518026
2013 results in: http://www.ncbi.nlm.nih.gov/pubmed/23796235
2013 results in: http://www.ncbi.nlm.nih.gov/pubmed/23786655
Publication citations
-
Results
Gordon AC, Russell JA, Walley KR, Singer J, Ayers D, Storms MM, Holmes CL, Hébert PC, Cooper DJ, Mehta S, Granton JT, Cook DJ, Presneill JJ, The effects of vasopressin on acute kidney injury in septic shock., Intensive Care Med, 2010, 36, 1, 83-91, doi: 10.1007/s00134-009-1687-x.
-
Results
Russell JA, Walley KR, Vasopressin and its immune effects in septic shock., J Innate Immun, 2010, 2, 5, 446-460, doi: 10.1159/000318531.
-
Resutls
Russell JA, Bench-to-bedside review: Vasopressin in the management of septic shock., Crit Care, 2011, 15, 4, 226, doi: 10.1186/cc8224.
-
Results
Gordon AC, Wang N, Walley KR, Ashby D, Russell JA, The cardiopulmonary effects of vasopressin compared with norepinephrine in septic shock., Chest, 2012, 142, 3, 593-605, doi: 10.1378/chest.11-2604.
-
Results
Russell JA, Fjell C, Hsu JL, Lee T, Boyd J, Thair S, Singer J, Patterson AJ, Walley KR, Vasopressin compared with norepinephrine augments the decline of plasma cytokine levels in septic shock., Am. J. Respir. Crit. Care Med., 2013, 188, 3, 356-364, doi: 10.1164/rccm.201302-0355OC.
-
Russell JA, Walley KR, Singer J, Gordon AC, Hébert PC, Cooper DJ, Holmes CL, Mehta S, Granton JT, Storms MM, Cook DJ, Presneill JJ, Ayers D, , Vasopressin versus norepinephrine infusion in patients with septic shock., N. Engl. J. Med., 2008, 358, 9, 877-887, doi: 10.1056/NEJMoa067373.
-
Results
Mehta S, Granton J, Gordon AC, Cook DJ, Lapinsky S, Newton G, Bandayrel K, Little A, Siau C, Ayers D, Singer J, Lee TC, Walley KR, Storms M, Cooper DJ, Holmes CL, Hebert P, Presneill J, Russell JA; Vasopressin and Septic Shock Trial (VASST) Investigators, Cardiac ischemia in patients with septic shock randomized to vasopressin or norepinephrine, Crit Care, 2013, 17, 3, R117, doi: 10.1186/cc12789.