Optimal VAsopressor TitraTION in patients 65 years and older (OVATION-65): protocol and statistical analysis plan for a randomised clinical trial

Masse, Marie-Hélène; Battista, Marie-Claude; Wilcox, M. Elizabeth; Pinto, Ruxandra; Marinoff, Nicole; D’Aragon, Frédérick; St-Arnaud, Charles; Mayette, Michaël; Leclair, Marc-André; Martinez, Hector Quiroz; Grondin-Beaudoin, Brian; Poulin, Yannick; Carbonneau, Élaine; Seely, Andrew J. E.; Watpool, Irene; Porteous, Rebecca; Chassé, Michaël; Lebrasseur, Martine; Lauzier, François; Turgeon, Alexis F.; Bellemare, David; Mehta, Sangeeta; Charbonney, Emmanuel; Belley‐Côté, Emilie P.; Botton, Edouard; Cohen, Dian; Lamontagne, François; Adhikari, Neill K. J.; members, Ovation team

doi:10.1136/bmjopen-2020-037947

Cited by 4 publications

(6 citation statements)

References 54 publications

(68 reference statements)

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“…Future trials might benefit from more precise hemodynamic monitoring and strict adherence to MAP goals [25]. Newer ongoing RCT, like Optimal VAsopressor TitraTION in patients 65 years and older (OVATION-65 trial) will evaluate the impact of MAP goals specifically on biological markers of end organs, which will likely improve our understanding further [26].…”

Section: Discussionmentioning

confidence: 99%

Mean Arterial Pressure Goal in Critically Ill Patients: A Meta-Analysis of Randomized Controlled Trials

2022

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Background: Current guidelines recommend targeting a mean arterial pressure (MAP) goal of 65 mm Hg or more in critically ill medical patients. Prospective studies have shown that a higher MAP goal can improve survival and decrease end-organ damage. However, randomized controlled trials (RCTs) have failed to show similar results. Thus, we performed this meta-analysis to evaluate whether a high MAP goal compared to a standard or low MAP goal will improve clinical outcomes in critically ill medical patients. Methods:We searched electronic databases for RCTs comparing standard MAP goals versus high MAP goals in critically ill medical patients. A standard MAP goal was defined as a MAP of 60 -70 mm Hg, and a MAP of 70 mm Hg or more was considered a high MAP goal. Outcomes of interest were mortality, duration of mechanical ventilation, and intensive care unit (ICU) length of stay. Subgroup analysis was performed based on the type of critically ill patients: cardiac arrest and septic shock. We used random-effects meta-analysis to estimate risk ratio (RR) with a 95% confidence interval (CI) for a dichotomous outcome. For continuous outcomes, the inverse variance method was used to calculate the standardized mean difference (SMD) with 95% CI. A P value of 0.05 or less was considered significant.Results: Six RCTs with a total of 3,753 patients (standard MAP goal: n = 1,872 and high MAP goal: n = 1,881) were included in the final analysis. Both standard/low MAP goal and high MAP goal were associated with similar risk for mortality (RR 0.94, 95% CI (0.87, 1.01), P = 0.11), duration of mechanical ventilation (SMD 0.51, 95% CI (-0.29, 1.31), P = 0.21) and ICU length of stay (SMD 0.22, 95% CI (-0.07, 0.5), P = 0.14). Subgroup analysis in cardiac arrest patient showed decreased ICU stay (SMD 0.55, 95% CI (0.31, 0.80), P < 0.000001) in patients with higher MAP goal compared to the stand-ard MAP goal group without any difference in mortality or duration of mechanical ventilation. Subgroup analysis of patients with septic shock had similar outcomes in both MAP targets. Conclusions:In critically ill patients, a higher MAP goal of > 70 mm Hg was associated with a similar risk of mortality, duration of mechanical ventilation, and ICU length of stay when compared with a standard MAP goal of 60 -70 mm Hg.

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Section: Discussionmentioning

confidence: 99%

Mean Arterial Pressure Goal in Critically Ill Patients: A Meta-Analysis of Randomized Controlled Trials

2022

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“…In total, 3,496 patients were randomized in 3 trials conducted in Canada, France, United States, and United Kingdom ( Table 1 ). A fourth trial, Optimal VAsopressor TitraTION in patients 65 years and older (OVATION-65), will be eligible but its results are not yet available ( 29 ). In one trial, patient eligibility was restricted to septic shock ( 27 ), whereas the other trials ( 4 , 28 ) enrolled patients with vasodilatory hypotension of any etiology (as defined by treating teams).…”

Section: Resultsmentioning

confidence: 99%

Lower Versus Higher Exposure to Vasopressor Therapy in Vasodilatory Hypotension: A Systematic Review With Meta-Analysis*

Richards-Belle¹,

Hylands²,

Muttalib³

et al. 2022

Critical Care Medicine

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Balancing the risks of hypotension and vasopressor-associated adverse effects is a daily challenge in ICUs. We conducted a systematic review with meta-analysis to examine the effect of lower versus higher exposure to vasopressor therapy on mortality among adult ICU patients with vasodilatory hypotension. DATA SOURCES:We searched Ovid Medline, Embase, and the Cochrane Central Register of Controlled Trials for studies published from inception to October 15, 2021. STUDY SELECTION:We included randomized controlled trials of lower versus higher exposure to vasopressor therapy in adult ICU patients with vasodilatory hypotension without language or publication status limits. DATA EXTRACTION:The primary outcome was 90-day all-cause mortality, with seven prespecified subgroups. Secondary outcomes included shorter-and longer-term mortality, use of life-sustaining therapies, vasopressor-related complications, neurologic outcome, and quality of life at longest reported follow-up. We conducted random-effects meta-analyses to calculate summary effect measures across individual studies (risk ratio [RR] for dichotomous variables, mean difference for continuous variables, both with 95% CIs). The certainty of the evidence was assessed using Grading of Recommendations, Assessment, Development, and Evaluation. We registered this review on the International Prospective Register of Systematic Reviews (CRD42021224434).DATA SYNTHESIS: Of 3,403 records retrieved, 68 full-text articles were reviewed and three eligible studies included. Lower exposure to vasopressors probably lowers 90-day mortality but this is based on moderate-certainty evidence, lowered for imprecision (RR, 0.94; 95% CI, 0.87-1.02). There was no credible subgroup effect. Lower vasopressor exposure may also decrease the risk of supraventricular arrhythmia (odds ratio, 0.55; 95% CI, 0.36-0.86; low certainty). CONCLUSIONS:In patients with vasodilatory hypotension who are started on vasopressors, moderate-certainty evidence from three randomized trials showed that lower vasopressor exposure probably lowers mortality. However, additional trial data are needed to reach an optimal information size to detect a clinically important 10% relative reduction in mortality with this approach.

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“…Multicenter observational study using data collected both prospectively and retrospectively to compare MAP of patients while receiving vasopressors before and during the Optimal VAsopressor TitratION in patients 65 years and older (OVATION-65) trial [ 11 ].…”

Section: Methodsmentioning

confidence: 99%

“…More information regarding the design of the OVATION-65 trial is available in the published protocol [ 11 ]. Briefly, the OVATION-65 trial enrolled 157 patients of 65 years of age or older who were receiving vasopressors for vasodilatory hypotension across seven Canadian sites (Fig.…”

Section: Methodsmentioning

confidence: 99%

“…Accordingly, when interpreting the result of a clinical trial with a usual care control arm, it is relevant to consider the extent to which the outcome of usual care in the trial corresponds to the outcome of usual care before the trial began. In 2018, we launched a clinical trial comparing a permissive hypotension strategy to reduce exposure to vasopressors vs. usual care in critically ill patients ( NCT03431181 ) [ 11 ]. Vasopressors are medications given intravenously that increase blood pressure via vasoconstriction and that are commonly used liberally by clinicians despite their potential side effects [ 12 – 14 ].…”

Section: Introductionmentioning

confidence: 99%

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The evolution of mean arterial pressure in critically ill patients on vasopressors before and during a trial comparing a specific mean arterial pressure target to usual care

et al. 2022

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Background In randomized clinical controlled trials, the choice of usual care as the comparator may be associated with better clinician uptake of the study protocol and lead to more generalizable results. However, if care processes evolve to resemble the intervention during the course of a trial, differences between the intervention group and usual care control group may narrow. We evaluated the effect on mean arterial pressure of an unblinded trial comparing a lower mean arterial pressure target to reduce vasopressor exposure, vs. a clinician-selected mean arterial pressure target, in critically ill patients at least 65 years old. Methods For this multicenter observational study using data collected both prospectively and retrospectively, patients were recruited from five of the seven trial sites. We compared the mean arterial pressure of patients receiving vasopressors, who met or would have met trial eligibility criteria, from two periods: [1] at least 1 month before the trial started, and [2] during the trial period and randomized to usual care, or not enrolled in the trial. Results We included 200 patients treated before and 229 after trial initiation. There were no differences in age (mean 74.5 vs. 75.2 years; p = 0.28), baseline Acute Physiology and Chronic Health Evaluation II score (median 26 vs. 26; p = 0.47) or history of chronic hypertension (n = 126 [63.0%] vs. n = 153 [66.8%]; p = 0.41). Mean of the mean arterial pressure was similar between the two periods (72.5 vs. 72.4 mmHg; p = 0.76). Conclusions The initiation of a trial of a prescribed lower mean arterial pressure target, compared to a usual clinician-selected target, was not associated with a change in mean arterial pressure, reflecting stability in the net effect of usual clinician practices over time. Comparing prior and concurrent control groups may alleviate concerns regarding drift in usual practices over the course of a trial or permit quantification of any change.

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Optimal VAsopressor TitraTION in patients 65 years and older (OVATION-65): protocol and statistical analysis plan for a randomised clinical trial

Cited by 4 publications

References 54 publications

Mean Arterial Pressure Goal in Critically Ill Patients: A Meta-Analysis of Randomized Controlled Trials

Mean Arterial Pressure Goal in Critically Ill Patients: A Meta-Analysis of Randomized Controlled Trials

Lower Versus Higher Exposure to Vasopressor Therapy in Vasodilatory Hypotension: A Systematic Review With Meta-Analysis*

The evolution of mean arterial pressure in critically ill patients on vasopressors before and during a trial comparing a specific mean arterial pressure target to usual care

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