An observational study in Systemic Inflammatory Response Syndrome (SIRS), Postoperative Vasodilation Syndrome and Stress Response, sponsored by University Hospital, Montpellier. Completed at 1 site in France. Open to participants aged 18 Years to 81 Years. Per ClinicalTrials.gov, last updated 2017-09-25.
Sponsored by University Hospital, Montpellier · Observational
The purpose of this study is to find a preoperative biomarker before cardiac surgery with cardiopulmonary bypass related to severe postoperative inflammatory response and circulatory complications. The investigators hypothesize that an increase of the preoperative stimulation of vasopressinergic system (in response to acute or chronic conditions) could lead to a microcirculatory dysfunction and favor the occurrence of vasodilatation during and after CPB and increase the symptoms of an inflammatory response after CPB. By defining a high risk population, a targeted strategy of monitoring and early or preventive treatment could improve postoperative prognosis.
The occurrence of a severe systemic inflammatory response syndrome (SIRS) after elective cardiac surgery with cardiopulmonary bypass (CPB) is estimated at about 20% of cases and is characterized by hemodynamic changes (tachycardia, hypotension, hypovolemia). It is also responsible for vasodilation with impaired microcirculation involving increased morbidity and mortality associated with organ dysfunction and the risk of bacterial translocation. However, the participation of vasopressinergic system in the functional impairment of microcirculation is unclear.
Copeptin is considered a marker of vasopressin secretion, deriving from the same precursor, being more stable and easy to dose. In a previous study of 64 patients with CPB, the investigators have shown that high copeptin preoperative levels are associated with the occurrence of vasodilatation syndrome after cardiac surgery (incidence 15%) with a relative deficiency of postoperative vasopressin.
Microcirculatory alterations can be explored through the study of tissue oxygenation by NIRS (StO2) at rest and in response to a hypoxic challenge (provided by brief vascular occlusion). In septic shock, altered recovery slopes of tissue oxygenation are associated with poor prognosis. The investigators could find similar impact on prognosis in cardiogenic shock if first hours of care did not improve this recovery slope.
The investigators hypothesize that an increase of the preoperative stimulation of vasopressinergic system (in response to acute or chronic conditions) could favor the occurrence of vasodilatation during and after CPB and increase the symptoms of an inflammatory response after CPB. The involvement of vasopressin in microcirculatory dysfunction is unknown.
This is a validation study of a predictive test for pathophysiology and prognosis. This study will be monocentric, prospective and observational in routine care.
The main end point of the study is to predict the onset of severe SIRS or postoperative vasodilation syndrome after CPB by the preoperative plasma copeptin level in a cardiac surgery population.
The secondary objectives are to assess the incidences of microcirculatory dysfunction, shock and organs failure after CPB, to determine the postoperative copeptin kinetics for patients with severe SIRS, to evaluate the prognosis with the ICU length of stay and D28 mortality.
Data are recorded prospectively on a paper case report form by ICU physicians in charge of the patients on the basis of clinical observation and electronic medical records. Quality assurance, monitoring and auditing are provided by the study promotor. Data will be checked by the main investigator to assess the accuracy and completeness of entered data into the CRF.
Patients are recruited during the preoperative period after screening of inclusion and exclusion criteria, delivering information and obtaining written consent.
Considering an expected sensitivity for predicting SIRS by preoperative copeptin on the order of 80%, the number of cases (subjects with severe SIRS) to be included for obtaining an estimate of the sensitivity with a lower limit of 95% to 55% is placed in 42 cases. Considering an incidence of severe SIRS at 20%, the total number of patients to be included in the study is 200. In our center the investigators perform 700 CPB / year, 70% met the criteria for inclusion.
For the primary objective, the predictive performance of preoperative copeptin for the occurrence of post-CPB severe SIRS will be evaluated by the construction of a ROC curve with finding an optimal threshold maximizing sensitivity and specificity (calculation of the Youden index) to be then estimated with their 95% confidence interval.
Regarding the secondary objectives, copeptin levels will be compared according to the presence of postoperative microcirculatory dysfunction, hemodynamic failure, organ dysfunction and preoperative factors using a reduced gap test. Univariate and multivariate analysis using linear regressions will be carried out to find the preoperative factors associated significantly and independently to high copeptin level. The postoperative kinetics of copeptin will be modeled using mixed linear regressions with an intercept +/- a random slope and taking into account the intra-individual correlation of the assays. The prognostic value of preoperative copeptin and postoperative StO2 recovery slope on D28 mortality will be analyzed using the ROC curve, determination of an optimal threshold using the Youden index and then calculating Sensitivity and specificity with their 95% confidence interval.
195 studies on the registry are indexed under Systemic Inflammatory Response Syndrome; 24 are open to participants now.
This study's enrollment of 200 is above the median of 134 across 94 observational studies indexed under Systemic Inflammatory Response Syndrome.
Browse Systemic Inflammatory Response Syndrome studies →University Hospital, Montpellier is the lead sponsor of 1,261 studies on the registry; 224 are open to participants now.
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Patients hospitalized and scheduled for cardiac surgery
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Patients with postoperative inflammatory response as defined by the occurrence of severe SIRS and/or postoperative vasodilation syndrome. Severe SIRS is defined by meeting at least 2 SIRS criteria during 6 consecutive hours or at least 3 SIRS criterias. Classical SIRS criteria include: temperature \>38,3 or \<36°C, heart rate \>90/min, respiratory rate \>20/min or PaCO2 \<32mmHg, GB\>12000 ou \<4000 c/mm3. Postoperative vasodilation syndrome is defined by the need of continuous infusion of norepinephrine (whatever the dose) to maintain the mean arterial pressure above 60 mmHg associated to a cardiac index above or egal to 2.2 L/min/m2. Patients without postoperative severe SIRS and without postoperative vasodilation syndrome
Diagnostic Test: Preoperative copeptin level
Measure of plasmatic copeptin from preoperative samples retained in a biorepository. Physicians are blinded to the result.
Also known as: Biomarker of vasopressin secretion, Systemic Inflammatory Response Syndrome (SIRS), Postoperative vasodilation syndrome, Stress response
Preoperative copeptin level
Plasmatic copeptine will be measured from routine blood sample on heparinazed tubes. The biological assay will be performed by Time-Resolved Amplified Cryptate Emission on automate Kryptor Compact plus (ThermoFisher, Clichy, France). A level above the 97° percentile of referent population will be considered pathological.
Time frame: Preoperative 24 hours
Postoperative microcirculatory impairment
Tissue oxygen saturation (STO2) measured at the thenar eminence by NIRS (Inspectra 650, Hutchinson Technologies) with application of a 3 min vascular occlusion test to measure the occlusion slope, the recovery slope and the hyperemic rebound. Microcirculatory dysfunction is defined by a recovery slope below 3%/s.
Time frame: Within 2h of admission in intensive care unit, before weaning of sedation and mechanical ventilation
Occurrence of SIRS using classical definition
SIRS is classically defined when 2 of the following criteria are met together: temperature \>38,3 or \<36°C, heart rate \>90/min, respiratory rate \>20/min or PaCO2 \<32mmHg, GB\>12000 ou \<4000 c/mm3.
Time frame: First postoperative 24 hours
Postoperative hemodynamical impairment
Occurrence of * A postoperative vasodilation syndrome defined by the need of continuous infusion of norepinephrine (whatever the dose) to maintain the mean arterial pressure above 60 mmHg associated to a cardiac index above or egal to 2.2 L/min/m2 * a postoperative low cardiac output syndrome defined by cardiac index below 2.2 L/min/m2 without hypovolemia, * a tissue hypoxia assessed by 2 consecutive lactate level above 2.2 mmol/l, * an hemorrhagic shock or * a septic shock.
Time frame: First postoperative 24 hours
Perioperative copeptin kinetics
Plasmatic copeptin will be measured from routine blood sample on heparinized tubes. The biological assay will be performed by Time-Resolved Amplified Cryptate Emission on automate Kryptor Compact plus (ThermoFisher, Clichy, France). A level above the 97° percentile of referent population will be considered pathological.
Time frame: 24 hours before the operation until admission intensive care unit
Perioperative copeptin kinetics
Plasmatic copeptin will be measured from routine blood sample on heparinized tubes. The biological assay will be performed by Time-Resolved Amplified Cryptate Emission on automate Kryptor Compact plus (ThermoFisher, Clichy, France). A level above the 97° percentile of referent population will be considered pathological.
Time frame: postoperative day
Global organs dysfunction
Assessed by the Sequencial Organ Failure Assessment (SOFA) score calculated at the postoperative day
Time frame: First postoperative 24 hours
Lengh of mechanical ventilation
Length (hours) of postoperative invasive mechanical ventilation
Time frame: Up to 28 days
Acute kidney injury
Defined and classified according to KDIGO criteria
Time frame: Up to 28 days
Renal replacement therapy
Incidence of patients requiring renal replacement therapy in ICU due to postoperative acute kidney injury
Time frame: Up to 28 days
Intensive Care Unit stay
Length (days) of postoperative intensive care unit stay
Time frame: through study completion, an average of 3 month
Hospital stay
Length (days) of postoperative hospital stay before current care ward discharge (excluding rehabilitation time)
Time frame: through study completion, an average of 3 month
Intensive Care Unit mortality rate
Intensive care unit mortality rate : death before ICU discharge
Time frame: Up to 28 days
Day 28 mortality rate
Overall mortality rate at 28 days after surgery
Time frame: Up to 28 days
Plan to share: No
Ran from Jan 2017 to primary completion in Jul 2017, 6 months.
Of 42 non-industry observational studies under Systemic Inflammatory Response Syndrome, half reached primary completion within 31 months of starting (the median), counting those still running; a quarter within 16 and three quarters within 55. This study's 6 months is below that.
Counting every sponsor, half of 47 studies reached it within 31 months; a quarter within 14 and three quarters within 55.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in May 2017. You cannot join it, but the record below documents what was studied.
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