Transcript M1: Study Overview

A pilot randomized controlled trial
Registry #: NCT 01800887
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Background & Study Rationale
Study Question
Study Design & Overview
Patient Population
Study Intervention
Outcomes
Shock is lethal + invariably treated
with vasopressors
Mortality 40% vs 34%
Mortality 39% vs 35%
Mortality 47% vs 31%
We have focused agents rather than
dosing strategies
And we typically do not worry about discordances between targets
and actual blood pressures
Mortality 39% vs 35%
Could dosing of vasopressors influence outcomes?
Farand et al. 2010
Could dosing of vasopressors influence outcomes?
Lamontagne et al. 2011
The OVATION question
Considering :
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Distributive shock is common
Patients with distributive shock are extremely vulnerable
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Because of their underlying chronic comorbidities
Acute instability
Vasopressors are used in almost every patient with distributive shock
Vasopressors are potent medications with potential for both benefit and harm
We are asking
In critically ill patients in shock, does titrating
vasopressors to higher blood pressure targets (liberal
vasopressor use - mean arterial pressure 75 to 80
mmHg) versus lower targets (restrictive vasopressor
use – mean arterial pressure 60 to 65 mmHg) result in
reduced hospital mortality?
The OVATION pilot RCT question
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Is it feasible to conduct a randomized controlled trial in
patients in shock from various aetiologies who receive
vasopressors comparing titration of vasopressor therapy
to higher blood pressure targets (liberal approach - mean
arterial pressure 75 to 80 mmHg) versus lower targets
(restrictive approach - 60 to 65 mmHg)?
Study Design
Pilot
N=80
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Inclusion Criteria
Older than 16 years of age at the time of consent
Under the direct care of the ICU team regardless of
location
Who have receive a minimum of 30 mL/kg of intravenous
fluids (2100 mL for a 70 kg patient) before enrolment OR
the most responsible physician has good reasons to
believe that more fluid resuscitation is no longer required
and could be harmful.
The treating physician believes will need vasopressors for
at least 6 hours once enrolled
Exclusion Criteria
We will exclude patients who meet at least one of the following
criteria.
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Have received vasopressors for more than 24 hours
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Are judged by the treating physician to be in obvious cardiogenic
shock after an acute myocardial infarction (based on new ST
segment elevations on ECG or obvious echocardiographic findings)
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Have obvious haemorrhagic shock as a consequence of a clearly
identified source of blood loss
4.
Require vasopressors after cardiac surgery as a result of
cardiopulmonary bypass-induced hypotension
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Who have a specific indication for catecholamine therapy other
than shock (i.e. angioedema or intracranial hypertension)
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The attending team has agreed to withhold or withdraw life
sustaining Tx
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Concurrent enrollment in interventional trials that do not meet
guidelines for co-enrolment (co-enrolment is permissible if there is
no potential interaction between the protocols; this will be
addressed case by case)
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Prior randomization in this study
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Standard of Care plus one of the following:
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Liberal Approach: vasopressors titrated to a MAP of 75-80 mmHg
Restrictive Approach: vasopressors titrated to a MAP of 60-65
mmHg
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The primary outcome will be the difference in the
means of mean arterial pressures while on
vasopressors and we define acceptable adherence
(the threshold for feasibility) by a difference of at
least 5 mmHg while on vasopressors.
As secondary feasibility outcomes, we will also
capture the number of protocol violations.
Tertiary outcomes will explore clinical endpoints
such as tissue perfusion, organ dysfunction,
complications of vasopressor use, overall resource
use in each arm and mortality (ICU, hospital and 6month).
Thank you for taking the time to complete
this training module.
Proceed to Module 2: Patient Eligibility & Consent