Goal-Directed Therapy Following Cardiac Surgery

Study Overview
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Brief Summary
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Pilot prospective randomized control trial comparing goal-directed therapy algorithm vs routine care in the intensive care unit following cardiac surgery.

Detailed Description
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Rationale: Goal-directed therapy (GDT) has been shown to reduce complications and length of stay on cardiac surgery patients. Unfortunately, the existing literature on GDT in CV surgery has several limitations, which creates uncertainty over the expected benefit of implementing this care element with high associated costs and impact on workflow. Hypotension Prediction Index (HPI) is a proprietary algorithm that utilizes pulse contour analysis from invasive arterial pressure monitoring to identify patients at risk for becoming hypotensive within 15 minutes. The algorithm was developed using machine learning on a large surgical/ICU data set, and then externally validated on non-cardiac and cardiac surgical patients. HPI, as part of a GDT algorithm, may allow healthcare providers to identify patients recovering from cardiac surgery who may benefit from optimization prior to becoming hypotensive and assist with selecting the most appropriate hemodynamic intervention. Hypothesis: Application of an HPI-based GDT algorithm will result in a difference in cumulative fluid administration over the first 24-hours of index ICU admission following cardiac surgery. Study Design: Unblinded randomized controlled trial pilot. Data will be used to inform/justify the feasibility, design, and implementation of a future multi-center randomized controlled trial. Study Population: Moderate or high-risk (EuroSCORE II > 2%), non-emergent, adult open-heart cardiac surgery patients. Heart transplant, durable VAD implantation, or patients who require post-operative MCS support will be excluded. Sample size= 100 (50 control : 50 intervention) Intervention: Patients randomized to the intervention arm will be monitored using the HPI technology and be treated following a GDT algorithm when HPI is >50 for 48-hours or duration of invasive arterial monitoring (whichever occurs first). The GDT algorithm is a standardized approach to identifying abnormal hemodynamic parameters and administering a prescribed therapy in a step-wise fashion with fixed re-assessment intervals (see attached). What will be different from routine care? : Hemodynamic interventions (fluid, inotropic, or vasopressor therapy) will be administered when HPI > 50 rather than MAP < 65. Choice of applied therapy (fluid, inotropic, or vasopressor therapy) will be guided by a GDT algorithm.

Official Title
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Goal-Directed Therapy (GDT) Using Hypotension Prediction Index (HPI) Following Cardiac Surgery: a Pilot Randomized Control Trial

Conditions
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Surgery

Intervention / Treatment
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* Device: Goal-directed therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥ 18 years of age Planned cardiac surgery using cardiopulmonary bypass (sternotomy or MICS) Preoperative European System for Cardiac Operative Risk Evaluation II (EuroSCORE II) of 2% or more. Informed consent obtained. Exclusion Criteria: Patients who refuse participation Patients who are unable to give informed consent Patients who are having a heart transplant or having surgery solely for an insertion of a ventricular assist device Emergency surgery Patients who require MCS (including ECMO, Impella, or IABP) post-operatively

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Control<br>Routine post-operative clinical care. | |
| Experimental: Intervention<br>Goal-directed therapy algorithm in addition to routine post-operative clinical care. | Device: Goal-directed therapy<br>* Goal-directed therapy using HemoSphere® monitor, Acumen® transducer, and Hypotension Prediction Index® algorithm (Edwards Lifesciences, Irvine, USA),<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 24-hour cumulative IV fluid administration | Cumulative post-operative intravenous fluid administration over the first 24-hours of index ICU admission. | 24-hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fluid Administration | Daily average | Duration of ICU stay, up to 30-days | 
| Fluid Administration | Cumulative | Duration of ICU stay, up to 30-days | 
| Vasoactive medication administration | Daily average | Duration of ICU stay, up to 30-days | 
| Vasoactive medication administration | Daily cumulative | Duration of ICU stay, up to 30-days | 
| Vasoactive medication administration | Duration | Duration of ICU stay, up to 30-days | 
| Hemodynamic parameters | Incidence of HPI > 50 greater than 5-minutes | 48-hours or when arterial line removed | 
| Hemodynamic parameters | Incidence of HPI > 85 greater than 5-minutes | 48-hours or when arterial line removed | 
| Hemodynamic parameters | Incidence of MAP < 65 greater than 5-minutes | 48-hours or when arterial line removed | 
| Hemodynamic parameters | Total Area Under the Curve (AUC) for HPI > 50 | 24-hours | 
| Hemodynamic parameters | Total Area Under the Curve (AUC) for HPI > 50 | 48-hours or when arterial line removed | 
| Hemodynamic parameters | Total Area Under the Curve (AUC) for HPI > 85 | 24-hours | 
| Hemodynamic parameters | Total Area Under the Curve (AUC) for HPI > 85 | 48-hours or when arterial line removed | 
| Hemodynamic parameters | Total Area Under the Curve (AUC) for MAP < 65 | 24-hours | 
| Hemodynamic parameters | Total Area Under the Curve (AUC) for MAP < 65 | 48-hours or when arterial line removed | 
| Enrollment | Proportion of screened patients eligible for enrollment. | 1-year | 
| Enrollment | Proportion of eligible patients who consent to participate. | 1-year | 
| Study Protocol Compliance | Proportion of consented patients who complete all study assessments. | 1-year | 
| Arterial Monitoring Reliability | Number of arterial catheters requiring replacement | 1-year | 
| GDT algorithm compliance | Time from HPI > 50 to application of an intervention | 48-hours or when arterial line removed | 
| GDT algorithm compliance | Proportion of hemodynamic interventions applied for HPI > 50 that were recommended by the algorithm | 48-hours or when arterial line removed | 
| GDT algorithm compliance | Proportion of hemodynamic interventions applied for MAP < 65 that would be recommended by the algorithm based on hemodynamic parameters. | 48-hours or when arterial line removed | 
| GDT algorithm compliance | MD notifications prompted by the GDT algorithm and resulting actions | 48-hours or when arterial line removed | 
| GDT algorithm compliance | Actions (therapies or investigations) prompted by an MD notification. | 48-hours or when arterial line removed | 
| GDT algorithm compliance | Number of study protocol suspensions | 48-hours or when arterial line removed | 
| GDT algorithm compliance | Duration of protocol suspensions | 48-hours or when arterial line removed | 
| GDT algorithm compliance | Rationale for protocol suspensions | 48-hours or when arterial line removed | 
| End-organ dysfunction/injury | Acute kidney injury | Index admission, up to 30-days | 
| End-organ dysfunction/injury | Delirium | Index admission, up to 30-days | 
| End-organ dysfunction/injury | Stroke | Index admission, up to 30-days | 
| End-organ dysfunction/injury | Ileus | Index admission, up to 30-days | 
| End-organ dysfunction/injury | Gut infarction | Index admission, up to 30-days | 
| End-organ dysfunction/injury | Prolonged mechanical ventilation (> 24 hours) | Index admission, up to 30-days | 
| End-organ dysfunction/injury | Deep sternal wound infection | Index admission, up to 30-days | 
| End-organ dysfunction/injury | Any surgical site infection | Index admission, up to 30-days | 
| Transfusion | Total red-blood cell administration | Index admission, up to 30-days | 
| Transfusion | Total fresh-frozen plasma administration | Index admission, up to 30-days | 
| Transfusion | Total platelet administration | Index admission, up to 30-days | 
| Transfusion | Total albumin administration | Index admission, up to 30-days | 
| Mobilzation | Time to first mobilization (dangle) | Index admission, up to 30-days | 
| Mobilzation | Time to first mobilization (stand) | Index admission, up to 30-days | 
| Mobilization | Time to first mobilization (walk) | Index admission, up to 30-days | 
| Hydration | Time to first PO hydration | Index admission, up to 30-days | 
| Nutrition | Time to first PO nutrition | Index admission, up to 30-days | 
| Patient-centered Outcome | Quality of Recovery-15 (QOR-15) at post-op days 3, 5, 7, and 10. | Index admission, up to 10-days | 
| Patient-centered Outcome | World Health Organization Disability Assessment Schedule (WHODAS 2.0) at baseline, 2-weeks, 30-days, 90-days, and 1-year. | Up to 1-year post-operative | 
| Patient-centered Outcome | MacNew Questionnaire at baseline, 2-weeks, 30-days, 90-days, and 1-year. | Up to 1-year post-operative | 
| Patient-centered Outcome | The Depression, Anxiety and Stress Scale - 21 Items (DASS-21) at baseline, 2-weeks, 30-days, 90-days, and 1-year. | Up to 1-year post-operative | 
| Patient-centered Outcome | Canadian Patient Experiences Survey on Inpatient Care (CPES-IC) at 30-days | 30-days | 
| Length of Stay | ICU length of stay | Up to 1-year post-operative | 
| Length of Stay | Hospital length of stay | Up to 1-year post-operative | 
| Re-admission | Incidence of hospital re-admission within 30-days of index surgery | 30-days | 
| Mortality | 7-day, 30-day, and 1-year mortality. | Up to 1-year post-operative | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cardiac surgery, hemodynamic optimization, goal-directed therapy