Condition category
Infections and Infestations
Date applied
Date assigned
Last edited
Retrospectively registered
Overall trial status
Recruitment status
No longer recruiting
Publication status

Plain English Summary

Not provided at time of registration

Trial website

Contact information



Primary contact

Dr James Andrew Russell


Contact details

St Paul's Hospital
Rm 240 Comox Building
1081 Burrard Street
V6Z 1Y6
+1 604 806 2872

Additional identifiers

EudraCT number number

Protocol/serial number


Study information

Scientific title

A randomised controlled trial of VAsopressin versus norepinephrine in Septic Shock



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


Secondary study design

Randomised controlled trial

Trial setting

Not specified

Trial type


Patient information sheet


Septic Shock


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



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


Overall trial end date


Reason abandoned (if study stopped)


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


Age group




Target number of participants


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


Recruitment end date



Countries of recruitment


Trial participating centre

St Paul's Hospital
V6Z 1Y6

Sponsor information


University of British Columbia (Canada)

Sponsor details

2075 Wesbrook Mall
V6T 1Z1
+1 604 822 2454

Sponsor type




Funder type

Research organisation

Funder name

Canadian Institutes of Health Research (CIHR) (Canada) - (ref: MCT-44152)

Alternative name(s)

Funding Body Type

Funding Body Subtype


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:
2010 results in:
2010 results in:
2011 resutls in:
2012 results in:
2013 results in:
2013 results in:
2018 results in: (added 01/10/2019)

Publication citations

  1. 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.

  2. 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.

  3. Resutls

    Russell JA, Bench-to-bedside review: Vasopressin in the management of septic shock., Crit Care, 2011, 15, 4, 226, doi: 10.1186/cc8224.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

Additional files

Editorial Notes

01/10/2019: Publication reference added.