The Vasopressin in Pediatric Vasodilatory Shock Trial

ISRCTN	ISRCTN11597444
DOI	https://doi.org/10.1186/ISRCTN11597444
Protocol serial number	KC1; MCT-80549
Sponsor	Childrens Hospital of Eastern Ontario Research Institute (CHEORI) (Canada)
Funders	Canadian Institutes of Health Research (CIHR) (Canada) - http://www.cihr-irsc.gc.ca (ref: MCT-80549), Toronto Hospital for Sick Children Foundation (Canada), Physician's Services Incorporated (PSI) Foundation (Canada), Ferring Pharmaceuticals (Canada), Added as of 20/12/2007:, Laerdal Inc. (Canada), Queen's University Research Fund (Canada), Canadian Intensive Care Foundation (Canada), Heart and Stroke Foundation of Ontario (Canada)

Submission date: 10/06/2003
Registration date: 08/09/2003
Last edited: 26/01/2012

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 of protocol

Not provided at time of registration

Contact information

Dr Karen Choong
Scientific

Hamilton Health Sciences
1200 Main St. W.
Room 3G49
Hamilton
L8N 3Z5
Canada

Phone	+1 905 521 2100 ext. 76610
Email	choongk@mcmaster.ca

Study information

Primary study design	Interventional
Study design	Added as of 20/12/2007: Multicentre randomised double blind two armed placebo controlled parallel group trial with study participant, study investigator, caregiver, and data analyst blinded.
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
Scientific title	Vasopressin in pediatric vasodilatory shock: a multicentre, two armed, placebo controlled randomised parallel trial
Study acronym	VIP Trial
Study objectives	Current hypothesis as of 20/12/2007: In pediatric patients with vasodilatory shock who are refractory to standard vasoactive agents, low dose arginine vasopressin (AVP) will maintain adequate blood pressure and perfusion, thus reducing standard vasoactive infusion requirements. Previous hypothesis: "Warm shock" is a condition that occurs due to a variety of causes, and results in a significant number of deaths in both adults and children. The primary mechanism of death in warm shock is low blood pressure, which leads to inadequate blood and oxygen supply to vital organs. Multiple drugs have been used to control blood pressure and reverse shock, however patients often remain resistant to these medications. Hence side effects of these drugs are often seen, before their proposed effect occurs. Vasopressin, a drug which has been used for over 50 years for other conditions, has recently been shown to improve blood pressure in shock, where other drugs have failed. It appears to act directly to reverse the underlying mechanisms of shock, and has additional advantages over traditionally used medications. We are conducting a study to examine if vasopressin is effective and safe to use in critically ill children who suffer from warm shock. Please note that as of 20/12/2007 this trial record was extensively updated with information from the funder, the Canadian Institutes of Health Research (CIHR). All updates are recorded under the date 20/12/2007. The anticipated start and end dates of this trial have also been updated; the previous anticipated start and end dates of this trial were: Anticipated start date: 01/10/2006 Anticipated end date: 30/09/2007
Ethics approval(s)	Added as of 20/12/2007: Ethics approval received from the Research Ethics Board of Hamilton Health Sciences (Ontario) on the 21st May 2003 (ref: 03-157).
Health condition(s) or problem(s) studied	Pediatric vasodilatory shock
Intervention	Current interventions as of 20/12/2007: 1. Pressyn® AR, dose: 0.0005 units/kg/min, duration: until the patient is weaned off all open-labelled vasoactive agents 2. Placebo (normal saline), administered at the same volume, rate (maximum mls/hour) and duration as the active study drug Previous interventions: Patients will be randomized to receive an intravenous (IV) infusion of either low dose Arginine Vasopressin (AVP) (0.0005 u/kg/min to 0.002 u/kg/min) or placebo, in addition to the open labeled catecholamine pressors which they are already receiving. The study drug infusion will be titrated to a target mean arterial blood pressure appropriate for age. Contact for public queries: Barbara Murchison RN, CCRP Research Coordinator, Chalmers Research Group CHEO Research Institute 401 Smyth Road, Room 212B Ottawa, Ontario Canada K1H 8L1 Tel: +1 613 737 7600 ext. 4133 Fax: +1 613 738 4800 Email: bmurchison@cheo.on.ca website: http://www.chalmersresearch.com The previous sponsor for this trial was Hamilton Health Sciences (Canada). This has been updated on 20/12/2007.
Intervention type	Drug
Phase	Not Applicable
Drug / device / biological / vaccine name(s)	Vasopressin
Primary outcome measure(s)	Added as of 20/12/2007: Time to vasoactive-free hemodynamic stability measured as time in hours from study drug administration to time when all vasopressor/inotropic agents are successfully discontinued.
Key secondary outcome measure(s)	Added as of 20/12/2007: 1. Multiple organ dysfunction syndrome (MODS), measured by Delta PELOD - difference between MODS at study entry and worst value recorded during pediatric intensive care unit (PICU) stay 2. Organ Failure Free Days, measured up to 30 days post study drug administration 3. Mortality measaured up to 30 days post study drug administration
Completion date	30/06/2007

Eligibility

Participant type(s)	Patient
Age group	Child
Lower age limit	1 Month
Upper age limit	18 Years
Sex	All
Target sample size at registration	69
Key inclusion criteria	Current inclusion criteria as of 20/12/2007: 1. Age: 1 month to 18 years, either sex 2. Vasodilatory shock: patient must be within 24 hours of fulfilling criteria 2.1. and 2.2.: 2.1. Fluid and catecholamine refractory shock: patient must fulfill criteria 2.1.1. and 2.1.2.: 2.1.1. Fluid administration (greater than or equal to 40 ml/kg crystalloid/colloid) 2.1.2. Minimum vasoactive infusion requirement for eligibility - either one of: 2.1.2.1. Dopamine greater than or equal to 10 µg/kg/min 2.1.2.2. Any dose of epinephrine, norepinephrine or phenylephrine 2.2. Clinical evidence of Vasodilation/Warm shock. These physical signs may be present at any time, including prior the institution of the vasoactive infusions listed in point 2.1.2.: patient must fulfill criteria 2.2.1., plus any two of the three criteria 2.2.2., 2.2.3. or 2.2.4. for eligibility: 2.2.1. Low diastolic blood pressure (BP) (as defined by diastolic BP less than half systolic BP value) 2.2.2. Tachycardia (as defined by heart rate [HR] greater than 2 SD for age) 2.2.3. Warm extremities 2.2.4. Flash capillary refill 3. Arterial line 4. Central venous line (a pulmonary artery catheter is optional) 5. Commitment of intensive care unit (ICU) team to full aggressive support 6. Informed consent: from parent or appropriate substitute decision-maker Previous inclusion criteria: 1. Pediatric patients with vasodilatory shock, despite volume resuscitation and catecholamine pressor administration 2. Children greater than 1 month and less than 18 years of age, either sex
Key exclusion criteria	Added as of 20/12/2007: 1. Terminal illness (death anticipated in 24 hours, or withholding therapy considered) 2. Pregnancy 3. Known history of hypersensitivity to exogenous vasopressin 4. Cardiac Index less than or equal to 2.5 L/min/m^2 after fluid resuscitation (this is in the event that a formal cardiac index measurement has been performed, e.g. by Echo or Swan Ganz catheter) 5. Severe hyponatremia (serum sodium less than 125 mM) not responding to water restriction 6. Known history of vasospastic diathesis, e.g. Raynaud's phenomenon 7. Concurrent use of intravenous vasodilator agents: i.e. sodium nitroprusside, within 12 hours of phenoxybenzamine use 8. Patient who has received intravenous vasopressin or vasopressin analogue within 24 hours of eligibility 9. Diagnosis of syndrome of inappropriate antidiuretic hormone secretion (SIADH) or Diabetes Insipidus 10. Inability to obtain informed consent 11. Previous enrollment in the VIP study
Date of first enrolment	01/09/2003
Date of final enrolment	30/06/2007

Locations

Countries of recruitment

Canada

Study participating centre

Hamilton Health Sciences

Hamilton
L8N 3Z5
Canada

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	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	01/10/2009		Yes	No
Results article	results	01/11/2011		Yes	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes