ESPERII

JRCT ID: jRCTs051240035

Registered date:16/05/2024

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Coronary artery disease, valvular disease, pericardial disease, cardiac tumors
• Date of first enrollment: 16/05/2024
• Target sample size: 56
• Study type: Interventional

Intervention(s)

Subject patients take synbiotics 3 times a day starting 10 days before surgery (up to 14 days).
We perform a stool sample after hospitalization and before surgery and first postoperative stool collection.
We start oral administration of synbiotics 3 times a day for 1 week.
Stool collection and analysis of intestinal microflora will be performed before discharge from the hospital. Exosome analysis (after induction of anesthesia, at the end of the surgery, 1 and 2 days after surgery, before discharge, and 3 months after discharge: Osaka University Health and Counseling Center will perform the analysis)
If surgery is postponed, patients are asked to take it 10 days before surgery (up to 14 days) and 1 week after the start of postoperative oral intake (censored if the patient is discharged)

Outcome(s)

Primary Outcome

Association between synbiotics oral administration and incidence of postoperative delirium within 1 week after surgery (delirium defined as ICDSC score of 3 or more points at least once).
Delirium is defined as a score of 3 or more at least once within 1 week.

Secondary Outcome

1) Incidence rate of MACE (major advanced cardiac event: 2.2 L/min/m2 or less (except for 2.2 L/min/m2 or less at ICU admission), new atrial fibrillation, myocardial infarction, stroke, or heart failure requiring hospitalization) within 3 months after surgery
2) Incidence of postoperative pneumonia,chest X-ray showing pneumonia, CRP (mg/dL) more than 0.3 during hospitalization
3) Incidence of reintubation after 6 hours after extubation
4) Incidence of surgery related infections, wound infection and mediastinitis requiring new antibiotics, within 3 months after surgery, total number of days of antibiotics administered
5) Incidence of postoperative acute kidney injury according to KDIGO criteria within 3 months after surgery
6) Incidence of postoperative liver dysfunction, AST or ALT more than 100 U/L within 3 months after surgery
7) Alteration of the bacterial composition of the intestinal microflora comparing the bacterial count of the preoperative intestinal microflora immediately after the start of the oral postoperative period and before discharge from the hospital.
8) Alterations in tissue-derived exosomes.
The effects of synbiotics will be examined by measuring exosomes derived from neurons, oligodendroglial cells, and astrocytes. (Changes will be examined chronologically after induction of anesthesia, at the end of surgery, on the first and second postoperative days, and before discharge from the hospital. In addition, a blood sample will be taken 3 months later to investigate the transition.The association with dementia-related substances will be evaluated.
Exosomes will be quantified by Osaka University Health and Counseling Center using an ELISA-based quantification method with a sandwich method of anti-exosome antibodies (CD-9) and anti-neuronal cell antibodies (CD171). The same sandwich method will be used for oligodendroglial cells and astrocytes. We have obtained results that neuronal-derived exosomes are significantly elevated in patients with delirium during cardiac surgery, and we will test whether suppression of delirium by synbiotics inhibits exosome release.
9) MMSE-J from preadmission to 3 months postoperatively, difference from baseline and variation starting from point 21
10) Length of postoperative ICU stay
11) Length of hospital stay
12) Mortality rate, 3 months postoperatively

Key inclusion & exclusion criteria

• Age minimum: >= 65age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1) Patients scheduled for cardiac surgery using cardiopulmonary bypass
2) Patients who have more than 10 days between registration and cardiac surgery
3) Patients who are 65 years of age or older at the time of consent
4) Patients who provided written informed consent.

Exclude criteria

1) Patients who take other probiotic or synbiotic preparations, within 2 weeks prior to the start of Synprotec until the end of the postoperative delirium evaluation.
2) Patients with an ICDSC score of 3 or higher or MMSE-J score of 21 or lower on the most recent examination prior to enrollment
3) Patients who have difficulty taking the Synprotec (e.g., difficulty taking orally, allergy to the test product, inability to comply with the dosing regimen, etc.)
4) Patients scheduled to receive a left ventricular assist device
5) Patients with a history of treatment for diseases associated with degeneration of the basal ganglia
6) Patients with a history of craniotomy
7) Patients taking antipsychotic drugs
8) Patients diagnosed with dementia and undergoing treatment
9) Patients diagnosed with infective endocarditis
10) Patients with a colostomy
11) Patients diagnosed with inflammatory bowel disease (Crohn's disease, ulcerative colitis) and under treatment
12) Patients diagnosed with and undergoing treatment for collagen disease
13) Patients who have received antibiotics within 2 weeks prior to providing consent
14) Patients who are judged by the principal investigator or subinvestigator to be inappropriate to participate in this study for any other reason.

Related Information

• Primary Sponsor: Yoshitani Kenji
• Source(s) of Monetary Support: Yakult Central Institute,National Cerebral and Cardio vascular Center