Assessment of Patients Undergoing Cardiac Surgery and Admitted to the Intensive Care Unit

Cardiac Disease Clinical Trial

— BraSIS-2  

Official title:

Assessment of Patients Undergoing Cardiac Surgery and Admitted to the Intensive Care Unit: an Observational, Prospective, Multicenter Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06154473
• Other study ID #: 5350-22
• Status: Recruiting
• Start date: September 1, 2023
• Est. completion date: November 2024

Study information

• Verified date: October 2023
• Source: Hospital Israelita Albert Einstein
• Contact: Renato CF Chaves, MD, MBA.
• Phone: +5511984481068
• Email: renato.carneiro[@]einstein.br
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The objective of this study is to investigate the incidence of death and early postoperative complications, identify potential risk factors, and examine the demographic characteristics of patients and epidemiology of cardiovascular procedures. Our hypothesis is that gaining a more comprehensive understanding of the characteristics of patients who undergo cardiac surgery has the potential to improve outcomes for this patient profile. Thus, information was sought regarding the patient characteristics, surgeries performed, anesthesia administered, incidence of intraoperative and postoperative complications, and risk factors associated with complication and mortality in the ICU. The main questions it aims to answer are:

• Incidence of mortality or severe postoperative complications that occur within the first 3 postoperative days or until discharge from the ICU.

• Risk factors associated with severe complications in patients who undergo cardiac surgery.

• Characteristics of patients, anesthesia and surgical procedures performed

• Incidence of severe intraoperative complications and moderate postoperative complications

• Evaluate the influence of accumulated fluid balance on outcomes, mortality, and length of ICU stay.

• Evaluate mortality in the ICU.

• Describe the risk factors associated with mortality.

Description:

BACKGROUND The results of procedures in patients undergoing cardiovascular surgery are significantly influenced by preoperative risk factors and adequate perioperative management. Therefore, it is essential to develop tools and strategies that provide improvements in care to minimize complications.

SAMPLE SIZE CALCULATION The aim is to consecutively include 500 patients who undergo cardiac surgery. The incidence of death or severe postoperative complications in cardiovascular surgery during the first 3 postoperative days or until discharge from the ICU is approximately 20%. Therefore, with the inclusion of 500 patients, it will be possible to create a robust regression model by adding 10 independent variables.

PRIMARY OBJECTIVE Outcome composed of mortality or severe postoperative complications within the first 3 postoperative days or until ICU discharge, whichever occurs first. Severe postoperative complications are: stroke, septic shock, unscheduled urgent or emergency surgical reoperation, cardiovascular complications, hematological complications, pulmonary complications, and renal complications.

Cardiovascular complications: acute myocardial infarction, unplanned use of circulatory assist device, cardiac arrest with return of spontaneous circulation, severe hemodynamic instability.

Hematologic complication: severe bleeding. Pulmonary complications: acute respiratory distress syndrome (ARDS) with partial pressure of oxygen (PaO2) / inspired oxygen fraction (FiO2) ratio ≤ 250 (refractory to rescue maneuvers and ventilatory adjustment that persists for more than 1 hour), re-intubation in an unplanned manner.

Renal complications: Kidney Disease: Improving Global Outcomes (Kdigo) score ≥ 2 or renal replacement therapy.

Severe hemodynamic instability was defined as: use of norepinephrine ≥0.1 mcg/kg/min for more than 2 hours; or adrenaline ≥0.1 mcg/kg/min for more than 2 hours; or dose-independent combination of norepinephrine and adrenaline for more than 2 hours; or dose-independent combination of norepinephrine and vasopressin for more than 2 hours. It is important to note that there is no consensus on the definition of severe hemodynamic instability in the postoperative period of patients undergoing cardiac surgery. The definition of severe hemodynamic instability was made after literature review and extensive discussion with the executive committee of the BraSIS 2 trial.

Acute myocardial infarction is recommended diagnosis using the universal type 5 infarction classification: troponin elevation 10 times the 99th percentile.

Major bleeding is defined as a fall ≥ 2g/dl hemoglobin or transfusion of 2 red blood cells concentrates without an increase in hemoglobin value or bleeding associated with a fall in systolic blood pressure value ≥10 millimeter of mercury (mmHg) when the patient assumes the orthostatic position or a spontaneous fall in systolic blood pressure ≥ 20 mmHg or an increase in heart rate ≥ 20 beats per minute.

The diagnosis of ARDS was made by using the Berlin definition. To diagnose ARDS using the Berlin definition, the respiratory failure could not fully be explained by cardiac failure or volume overload. To exclude volume overload secondary to cardiac failure, it is suggested to use B-type natriuretic peptide (BNP) or N-terminal pro B-type natriuretic peptide (NT-proBNP) in combination with echocardiography to assess cardiac function.

STATISTICAL ANALYSIS Data will be collected as part of routine clinical care. Patient characteristics will be compared and described by appropriate methods. Histogram and Kolmogorov-Smirnov test will be used to evaluate the distribution pattern of continuous numerical variables. Qualitative variables will be expressed as proportions, quantitative variables will be expressed as mean ± standard deviation or as median and interquartile range when appropriate.

Continuous variables will be analyzed with Student's t-test, analysis of variance, Mann-Whitney U test, Kruskal-Wallis test, or Friedman test as appropriate. Categorical variables will be analyzed with chi-square test or Fisher's exact test as appropriate.

Analyses of time dependent variables will be evaluated using the paired t-test (or Wilcoxon signed rank test in case of non-normal distribution) if time effect is detected, Cox regression and visualized by Kaplan-Meier curve.

Comparisons between and within group will be performed using analysis of variance (ANOVA) and post-hoc analyses for continuous variables. The multiple logistic regression model will be used to identify independent risk factors for postoperative complications. Sub-groups of patients undergoing open heart surgery and patients undergoing percutaneous cardiovascular surgery will be analyzed separately.

The following subgroup analyses will be performed: patients with prior use of circulatory assist devices compared to patients without prior use of such devices, patients with prior use of vasoactive drugs compared to patients without preoperative use, comparison between types of cardioplegic solutions used, comparisons between types of circulatory assist devices, impact of CPB time on mortality and postoperative complications, impact of intraoperative use of etomidate. All significance probabilities (p-values) presented will be two-tailed. The p-values will be considered statistically significant when smaller than 0.05 or 95% confidence interval (CI) values that do not cross the number 1.0. Bonferroni correction will be used for multiple comparisons in post hoc tests. R version 4.0.0 software (R Foundation for Statistical Computing, Austria) and Python programming language (version 3.10, python.org) will be used to perform the analyses.

ADVERSE EVENTS The study does not present additional risks to those expected for patients undergoing cardiac surgery. The only anticipated risk would be a breach of data confidentiality, which will be mitigated as described in the data confidentiality item. Adverse events are defined as an unwanted experience suffered by a patient during the study, whether or not related to the proposed interventions. All adverse events must be reported to the research ethics committee that approved the trial. It is emphasized that mortality in a patient undergoing cardiac surgery is an event frequently encountered in this patient population, and although it is an unwanted event, it will not be defined as an adverse event. A severe adverse event is any unfavorable medical occurrence or effect that results in

• Life threatening (during the occurrence of the event).

• Requires hospitalization or prolongs the length of stay for patients already hospitalized.

• Significant or persistent physical disability.

• Any new event that affects patient safety, such as an unexpected outcome of the test drug, lack of efficacy of the test drug, or increased safety found in another drug similar to the study drug recently found in animal studies, etc.

REGULATORY STATUS The study will be conducted in accordance with the principles of the Declaration of Helsinki and in accordance with the Medical Research Involving Humans Act.

APPROVAL FROM ETHICS AND REGULATORY AUTHORITIES The study will be performed according to the national and international guidelines. The Institutional Review Board of the Hospital Israelita Albert Einstein has approved this study (CAAE: 69330823.1.0000.0071). The participating centers will not initiate the study until they have obtained approval from their respective local Institutional Review Boards.The need for informed consent is determined by the Institutional Review Board of each participating center.

CONFIDENTIALITY OF DATA The patient and the investigating center will be identified by the corresponding number on the electronic data collection form. Researchers will keep the data obtained from the medical record confidential and store it in cabinets with restricted access. The anonymity of all data in interim and final reports will be ensured. The data will be treated confidentially, and sites should keep all data stored for the length of the study and for as long as local regulations allow. After the designated time, data should be incinerated. Loss of data confidentiality is possible due to access to patient data. However, staff undertakes to take every care to ensure confidentiality of the data.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 500
• Est. completion date: November 2024
• Est. primary completion date: September 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Adult patients (age 18 years or older).

• Cardiac surgeries requiring postoperative care in the ICU.

Exclusion Criteria:

• Exclusive palliative care or advance directive expressing desire for limitation of life support (cardiopulmonary resuscitation, invasive mechanical ventilation, renal replacement therapy).

• Moribund patient.

• Surgery for implant of cardiac implantable electronic device (implantable cardioverter defibrillator, cardiac pacemaker).

• Patients previously included in this study.

Related Conditions & MeSH terms

• Cardiac Disease
• Cardiac Ischemia
• Cardiac Valve Disease
• Coronary Artery Disease
• Heart Diseases
• Heart Valve Diseases
• Ischemia
• Myocardial Ischemia

Intervention

Procedure:
• Open heart surgery group.
Patients undergoing open heart surgery.
• Percutaneous cardiovascular surgery group.
Patients undergoing percutaneous cardiovascular surgery.

Locations

Country	Name	City	State
Brazil	Hospital Israelita Albert Einstein	São Paulo

Sponsors (1)

Lead Sponsor	Collaborator
Hospital Israelita Albert Einstein

Country where clinical trial is conducted

Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mortality or severe postoperative complications within the first 3 postoperative days or until ICU discharge, whichever occurs first	Severe postoperative complications are: stroke, septic shock, unscheduled urgent or emergency surgical reoperation, cardiovascular complications, hematological complications, pulmonary complications, and renal complications	Within the first 3 postoperative days or until ICU discharge, whichever occurs first, assessed up to 3 postoperative days
Secondary	Evaluate the characteristics of the patients	Describe demographic characteristics of the patients	Within the first 3 postoperative days or until ICU discharge, whichever occurs first, assessed up to 3 postoperative days
Secondary	Describe the surgeries performed	Describe the type of surgeries performed. Description of the surgery as: emergency, urgent and elective surgery; open heart surgery or percutaneous cardiovascular surgery; valve repair (or replacement) and/or coronary artery bypass grafting	Within the first 3 postoperative days or until ICU discharge, whichever occurs first, assessed up to 3 postoperative days
Secondary	Describe the anesthesia performed	The following anesthesia modalities will be considered and collected: general anesthesia, combined general anesthesia (general anesthesia and neuroaxis block) and sedation	Within the first 3 postoperative days or until ICU discharge, whichever occurs first, assessed up to 3 postoperative days
Secondary	Evaluate the incidence of severe intraoperative complications	The following severe intraoperative complications will be considered and collected: bronchospasm or difficulty with respiratory support, failure to exit cardiopulmonary bypass (CPB), cardiac arrest with return of spontaneous circulation, and excessive blood transfusion (= 4 units of packed red blood cells)	Within the first 3 postoperative days or until ICU discharge, whichever occurs first, assessed up to 3 postoperative days
Secondary	Assess the incidence of other postoperative complications (not included in the primary endpoint)	The following postoperative complications will be considered and collect: cardiovascular; pulmonary; neurological, gastrointestinal and metabolic	Within the first 3 postoperative days or until ICU discharge, whichever occurs first, assessed up to 3 postoperative days
Secondary	Evaluate the influence of fluid balance on ICU mortality	Evaluate the influence of fluid balance on ICU mortality. Determine if the increase in fluid balance during the ICU stay is associated with the increase in ICU mortality.	Within the first 3 postoperative days or until ICU discharge, whichever occurs first, assessed up to 3 postoperative days
Secondary	Assess the length of stay in the ICU	Calculated from the date and time of admission and date and time of actual ICU discharge (discharge or death)	Within the first 3 postoperative days or until ICU discharge, whichever occurs first, assessed up to 3 postoperative days
Secondary	Evaluate the risk factors associated with ICU mortality	To construct a logistic regression model to identify risk factors associated with increased ICU mortality.	Within the first 3 postoperative days or until ICU discharge, whichever occurs first, assessed up to 3 postoperative days