Vasopressin and Corticosteroids in septic Shock

ISRCTN	ISRCTN66727957
DOI	https://doi.org/10.1186/ISRCTN66727957
EudraCT/CTIS number	2009-017636-41
Secondary identifying numbers	UKCRN ID: 8828; EudraCT: 2009-017636-41

Submission date: 03/06/2010
Registration date: 10/09/2010
Last edited: 16/04/2015

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Signs and Symptoms

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English Summary

Not provided at time of registration

Contact information

Dr Anthony Gordon
Scientific

Clinical Senior Lecturer & Consultant
Critical Care Medicine
11N, Imperial College/Charing Cross Hospital
Fulham Palace Road
London
W6 8RF
United Kingdom

Email	anthony.gordon@imperial.ac.uk

Study information

Study design	Open-label randomised controlled trial
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Hospital
Study type	Treatment
Participant information sheet	Not available in web format, please use the contact details below to request a patient information sheet
Scientific title	Vasopressin and Corticosteroids in septic Shock: an open-label randomised controlled trial
Study acronym	VACS
Study hypothesis	This is an open-label randomised controlled trial. It will be conducted in the three general adult ICUs within the Imperial College Healthcare NHS Trust. All patients will be treated with vasopressin as the initial vasopressor therapy to maintain mean arterial blood pressure after adequate fluid resuscitation. If maximum doses of vasopressin are reached the patient will be treated with the randomised study drug (hydrocortisone or placebo), before additional clinically indicated vasopressors/inotropes are prescribed. The objectives of this trial are: 1. To assess if corticosteroids increase exogenously administered vasopressin levels in septic shock 2. To assess if corticosteroids increase the blood pressure response to exogenously administered vasopressin 3. To act as feasibility study for a larger double-blind randomised controlled trial As of 22/11/2011 the overalltrial end date has been updated. The previous date was 30/09/2011.
Ethics approval(s)	Oxford REC A, 18/05/2010, ref: 10/H0604/35
Condition	Topic: Generic Health Relevance and Cross Cutting Themes; Subtopic: Generic Health Relevance (all Subtopics); Disease: Critical Care
Intervention	Vasopressin +/- steroids; the two treatment arms will be: 1. Vasopressin (0 - 0.06 U/minute via continuous intravenous [IV] infusion) and hydrocortisone sodium phosphate (50 mg IV 6-hourly) 2. Vasopressin (0 - 0.06 U/minute via continuous IV infusion) and placebo (0.5 ml 0.9% saline IV 6 hourly) Vasopressin will continue until shock has resolved. Hydrocortisone will continue for a maximum of 11 days. Total follow-up is 28 days. Study entry: single randomisation only
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Not Applicable
Drug / device / biological / vaccine name(s)	Vasopressin, hydrocortisone
Primary outcome measure	Plasma vasopressin levels, measured 6 - 24 hours post-steroid administration
Secondary outcome measures	1. Difference in vasopressin requirements between treatment groups 2. 28-day, ICU and hospital mortality rates 3. Organ failure free days in the first 28 days, assessed using the serial organ failure assessment (SOFA) score
Overall study start date	30/08/2010
Overall study end date	31/03/2012

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	Both
Target number of participants	Planned sample size: 60; UK sample size: 60
Participant inclusion criteria	The target population is adult patients who require vasopressors for the management of sepsis despite fluid resuscitation. These patients will require management on the intensive care unit. Inclusion criteria will use the internationally-established consensus definitions of sepsis. In brief: 1. Fulfil 2/4 of the criteria of the systemic inflammatory response syndrome (SIRS) due to known or suspected infection within the previous 24 hours. The SIRS criteria are: 1.1. Fever (greater than 38°C) or hypothermia (less than 36°C) 1.2. Tachycardia (heart rate greater than 90 beats per minute) 1.3. Tachypnea (respiratory rate greater than 20 breaths per minute or partial pressure of carbon dioxide in the blood [PaCO2] less than 4.3 kPa) or need for mechanical ventilation 1.4. Abnormal leukocyte count (greater than 12,000 cells/mm3, less than 4000 cells/mm3, or greater than 10% immature [band] forms) 2. Hypotension despite adequate intravenous fluid resuscitation (minimum of 1 litre in the previous four hours) 3. Aged greater than or equal to 16 years, either sex
Participant exclusion criteria	1. Patient has received a continuous infusion of vasopressors previously during this hospital admission (other than vasopressors used as emergency treatment to stabilise the patient during this episode). Vasopressors include noradrenaline, adrenaline, vasopressin, dopamine, metaraminol, phenylephrine. 2. Regular systemic corticosteroid therapy within the previous three months (this does not include inhaled steroid therapy) 3. End-stage renal failure 4. Known adrenal dysfunction/insufficiency 5. Physician and team are not committed to full active care 6. Patient who is terminally ill (death anticipated within 24 hours) 7. Patient is known to be pregnant 8. Patient has known acute mesenteric ischaemia 9. Patient is being actively treated for an acute coronary syndrome 10. Patient is known to have Raynaud's phenomenon, systemic sclerosis or other vasospastic diseases 11. Patient is enrolled in another interventional trial that might interact with the study drugs 12. Patients has a history of anaphylaxis to any study drug
Recruitment start date	30/08/2010
Recruitment end date	31/03/2012

Locations

Countries of recruitment

England
United Kingdom

Study participating centre

Imperial College/Charing Cross Hospital

London
W6 8RF
United Kingdom

Sponsor information

Imperial College London (UK)
University/education

c/o Gary Roper
Joint Research Office
Sir Alexander Fleming Building
Exhibition Road
London
SW7 2AZ
England
United Kingdom

Phone	+44 (0)20 7594 1188
Email	gary.roper@imperial.ac.uk
Website	http://www3.imperial.ac.uk/clinicalresearchgovernanceoffice
"ROR"	https://ror.org/041kmwe10

Funders

Funder type

Government

Intensive Care Foundation (UK)

No information available

National Institute for Health Research
Government organisation / National government

Alternative name(s): National Institute for Health Research, NIHR Research, NIHRresearch, NIHR - National Institute for Health Research, NIHR (The National Institute for Health and Care Research), NIHR
Location: United Kingdom

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	01/06/2014		Yes	No
HRA research summary			28/06/2023	No	No