Condition category
Signs and Symptoms
Date applied
10/06/2003
Date assigned
08/09/2003
Last edited
26/01/2012
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Dr Karen Choong

ORCID ID

Contact details

Hamilton Health Sciences
1200 Main St. W.
Room 3G49
Hamilton
L8N 3Z5
Canada
+1 905 521 2100 ext. 76610
choongk@mcmaster.ca

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

KC1; MCT-80549

Study information

Scientific title

Vasopressin in pediatric vasodilatory shock: a multicentre, two armed, placebo controlled randomised parallel trial

Acronym

VIP Trial

Study hypothesis

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

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).

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.

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

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 names

Vasopressin

Primary outcome measures

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.

Secondary outcome measures

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

Overall trial start date

01/09/2003

Overall trial end date

30/06/2007

Reason abandoned

Eligibility

Participant 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

Participant type

Patient

Age group

Child

Gender

Both

Target number of participants

69 (added as of 20/12/2007)

Participant 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

Recruitment start date

01/09/2003

Recruitment end date

30/06/2007

Locations

Countries of recruitment

Canada

Trial participating centre

Hamilton Health Sciences
Hamilton
L8N 3Z5
Canada

Sponsor information

Organisation

Children’s Hospital of Eastern Ontario Research Institute (CHEORI) (Canada)

Sponsor details

c/o Ms. Laura Goyer
Assistant Grants Administrator
401 Smyth Road
Ottawa
Ontario
K1H 8L1
Canada
+1 613 737 7600 ext. 4165
lgoyer@cheo.on.ca

Sponsor type

Hospital/treatment centre

Website

http://www.cheori.org/

Funders

Funder type

Research organisation

Funder name

Canadian Institutes of Health Research (CIHR) (Canada) - http://www.cihr-irsc.gc.ca (ref: MCT-80549)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Toronto Hospital for Sick Children Foundation (Canada)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Physician's Services Incorporated (PSI) Foundation (Canada)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Ferring Pharmaceuticals (Canada)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Added as of 20/12/2007:

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Laerdal Inc. (Canada)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Queen's University Research Fund (Canada)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Canadian Intensive Care Foundation (Canada)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Heart and Stroke Foundation of Ontario (Canada)

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

Results - basic reporting

Publication summary

1. 2009 results in http://www.ncbi.nlm.nih.gov/pubmed/19608718
2. 2011 results in http://www.ncbi.nlm.nih.gov/pubmed/22007013

Publication citations

  1. Results

    Choong K, Bohn D, Fraser DD, Gaboury I, Hutchison JS, Joffe AR, Litalien C, Menon K, McNamara P, Ward RE, , Vasopressin in pediatric vasodilatory shock: a multicenter randomized controlled trial., Am. J. Respir. Crit. Care Med., 2009, 180, 7, 632-639, doi: 10.1164/rccm.200902-0221OC.

  2. Results

    Choong K, Arora S, Cheng J, Farrokhyar F, Reddy D, Thabane L, Walton JM, Hypotonic versus isotonic maintenance fluids after surgery for children: a randomized controlled trial., Pediatrics, 2011, 128, 5, 857-866, doi: 10.1542/peds.2011-0415.

Additional files

Editorial Notes