Impact of Non-invasive Individualized Goal-directed Fluid Therapy on Outcomes Following Thoracic Cancer Surgery

Study Overview
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Brief Summary
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High-risk patients scheduled for thoracic cancer surgery are increasing and theoretically eligible to perioperative individualized goal-directed fluid therapy (GDFT). However, thoracic surgery is challenging for intraoperative stroke volume (SV) and/or cardiac output monitoring because it requires lateral positioning, one-lung ventilation, and open-chest condition. Pulse contour analysis and esophageal Doppler have been proposed with contrasting results, whereas dynamic indices have been shown useless for predicting fluid responsiveness in that specific setting. Besides, more invasive technologies like thermodilution are not routinely used at the bedside by careproviders. Chest bioreactance seems to be a feasible, safe, rustic, easy-to-use, and plug-and-play method to non-invasively and continuously monitor SV and cardiac output in thoracic cancer surgery patients, able to detect significant spontaneous and pharmacologically-induced changes over time. To know if chest bioreactance could be used to conduct perioperative GDFT and impact patients 'outcome remains however to be demonstrated. Indeed, the routine fluid management in patients undergoing thoracic cancer surgery could be responsible of hypovolemia/hypoperfusion and/or hypervolemia/congestion leading to postoperative complications and poor outcomes. The present national prospective multicenter randomized simple blind study aims to demonstrate that an individualized goal-directed fluid therapy (GDFT) driven by chest bioreactance improves outcomes within 30 days in thoracic cancer surgery patients when compared with a standard of care. As double blind is not possible, an adjudication committee, whose members will be unaware of the procedure assignments, will adjudicate all the clinical outcomes.

Official Title
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Impact of Non-invasive Individualized Goal-directed Fluid Therapy on Outcomes Following Thoracic Cancer Surgery: A Multicenter, Randomized, Controlled Study

Conditions
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High-risk Thoracic Cancer Surgery

Intervention / Treatment
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* Device: individualized goal-directed fluid therapy by Starling device
* Device: group managed by standard of care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults (≥ 18 years old) High-risk patients (ASA score ≥ 3 and/or ventilatory deficit ≥ 30% and/or AKI risk index ≥ III (9) and/or RCRI > 2) undergoing elective open-chest or video-assisted thoracic cancer surgery Patients who have provided written informed consent to participate in the study Patients affiliated with a social health insurance Exclusion Criteria: Elective thoracic surgery other than cancer Emergency surgery (< 24h) Patients unable to understand the purpose of the study Patients participating in another trial that would interfere with this study Female patients who are pregnant, lactating or women of child-bearing potential without highly effective methods of contraception Female patients with positive β-HCG blood test Patients under judicial protection (guardianship, curatorship) Patients undergoing psychiatric treatment

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: National prospective multicenter randomized simple blind controlled study comparing a standard of care (control group) to an individualized strategy of intraoperative GDFT driven by non-invasive continuous SV monitoring via chest bioreactance (optimized group).
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Optimized group managed by the Starling device<br>In the optimized group, patients will be managed intraoperatively with the Starling device. It is a non-invasive fluid management monitoring system provides continuous hemodynamic monitoring and empowers fluid management across the continuum of care. Thanks to this device, patients will be managed according to the following protocol: fluid responsiveness will be systematically assessed by repetitive fluid challenges (2-3 ml/kg of Ringer Lactate) given to increase SV by at least 10% when mean arterial pressure falls below 65 mmHg and/or perfusion index falls below 1.5. Vasoactive and/or inotropic agents will be used at the discretion of the attending anesthesiologists in case of fluid unresponsiveness. | Device: individualized goal-directed fluid therapy by Starling device<br>* For patients in optimized group, fluids will be managed by Starling device during the thoracic cancer surgery.<br>|
| Other: Control group managed by standard of care<br>In the control group, patients will be managed intraoperatively at the discretion of the attending anesthesiologists, in accordance with their institutional protocols (i.e. fluids and/or vasoactive agents are given to maintain mean arterial pressure ≥ 65 mmHg). | Device: group managed by standard of care<br>* Patients will be managed intraoperatively at the discretion of the attending anesthesiologists, in accordance with their institutional protocols<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| A composite of postoperative complications rate adapted from the Clavien-Dindo classification with only events ≥ class II | It will be performed in each group and assessed by an independent adjudication committee. Clavien-Dindo classification : Class II : Pulmonary complications (any infection requiring antibiotics, non-invasive ventilation) Cardiovascular complications (postoperative atrial fibrillation (POAF) requiring treatment, deep venous thrombosis) Renal complications (acute kidney injury (AKI) stages 1 to 3 requiring fluid challenge or diuretics) Cerebral complications (delirium requiring treatment, stroke) Blood products transfusion Class III Reoperation from any cause Class IV Any admission to the intensive care unit (ICU) Class V Mortality from any cause The analysis of the main endpoint will be performed by a mixed logistic regression model. It will take into account as explanatory variable the intervention, as well as the type of surgery (open-chest or video-assisted). It will include a random intercept by center. | Within 30 days after the surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Each item of the primary composite endpoint between both groups | Items of the primary composite endpoint : - Pulmonary complications rate Each item of the primary composite endpoint will be described in each group in terms of number/percentage of patients and compared using the chi-2 test or the exact test of Fisher. An Holm correction will be applied to take into account multiple testing. | Within 30 days after the surgery | 
| Each item of the primary composite endpoint between both groups | Items of the primary composite endpoint : - Cardiovascular complications rate Each item of the primary composite endpoint will be described in each group in terms of number/percentage of patients and compared using the chi-2 test or the exact test of Fisher. An Holm correction will be applied to take into account multiple testing. | Within 30 days after the surgery | 
| Each item of the primary composite endpoint between both groups | Items of the primary composite endpoint : - Renal complications rate Each item of the primary composite endpoint will be described in each group in terms of number/percentage of patients and compared using the chi-2 test or the exact test of Fisher. An Holm correction will be applied to take into account multiple testing. | Within 30 days after the surgery | 
| Each item of the primary composite endpoint between both groups | Items of the primary composite endpoint : - Cerebral complications rate Each item of the primary composite endpoint will be described in each group in terms of number/percentage of patients and compared using the chi-2 test or the exact test of Fisher. An Holm correction will be applied to take into account multiple testing. | Within 30 days after the surgery | 
| Each item of the primary composite endpoint between both groups | Items of the primary composite endpoint : - Blood products transfusion rate Each item of the primary composite endpoint will be described in each group in terms of number/percentage of patients and compared using the chi-2 test or the exact test of Fisher. An Holm correction will be applied to take into account multiple testing. | Within 30 days after the surgery | 
| Each item of the primary composite endpoint between both groups | Items of the primary composite endpoint : - Reoperation from any cause rate Each item of the primary composite endpoint will be described in each group in terms of number/percentage of patients and compared using the chi-2 test or the exact test of Fisher. An Holm correction will be applied to take into account multiple testing. | Within 30 days after the surgery | 
| Each item of the primary composite endpoint between both groups | Items of the primary composite endpoint : - Any admission to the ICU rate Each item of the primary composite endpoint will be described in each group in terms of number/percentage of patients and compared using the chi-2 test or the exact test of Fisher. An Holm correction will be applied to take into account multiple testing. | Within 30 days after the surgery | 
| Each item of the primary composite endpoint between both groups | Items of the primary composite endpoint : - Mortality rate Each item of the primary composite endpoint will be described in each group in terms of number/percentage of patients and compared using the chi-2 test or the exact test of Fisher. An Holm correction will be applied to take into account multiple testing. | Within 30 days after the surgery | 
| Length of stay in hospital (days) and number/percentage of patients with length of stay in hospital ≥ 5 days in each group | Quantitative secondary endpoints will be described in each group, and will be compared between the two groups using the t test of Student or the test of Mann and Whitney, according to the shape of the distribution. Qualitative secondary outcome will be described in each group by the number/percentage of patients and compared using the chi-2 test or the exact test of Fisher. | 5 days | 
| APGAR surgical score and number/percentage of patients with APGAR surgical score < 7 in each group | Quantitative secondary endpoints will be described in each group, and will be compared between the two groups using the t test of Student or the test of Mann and Whitney, according to the shape of the distribution. Qualitative secondary outcome will be described in each group by the number/percentage of patients and compared using the chi-2 test or the exact test of Fisher. | 1 day | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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thoracic cancer surgery, goal-directed fluid therapy, Chest bioreactance