PBM as Strategy to CABG Anemic Patients Bypass Graft (CABG)

Phase 2

Recruiting

• Conditions: Coronary Disease; Coronary Artery Disease; Systemic Inflammatory Response; Anemia; Bleeding; Coronary Occlusion; Epigenetic Disorder; Coronary Stenosis
• Interventions: Procedure: blood transfusion; Drug: Erythropoietin

• Registration Number: NCT06542393
• Lead Sponsor: Federal University of São Paulo

Brief Summary

Anemia poses risks during coronary artery bypass grafting (CABG), increasing complications and mortality rates. Blood transfusions in cardiac surgery have negative outcomes, prompting the use of erythropoietin in Patient Blood Management (PBM) to limit transfusion needs and enhance postoperative recovery. EPO can reduce blood component requirements, adverse events, and inflammation in anemic CABG patients. A study aims to minimize transfusions through a PBM anemia treatment protocol for CABG patients, comparing outcomes in three groups: a Control Group (CG), a Non-PBM Group (NPBMG) treated with blood components, and a PBM Group (GPBM) treated with EPO. Parameters include post-op stay, mortality, cardiovascular events, non-cardiovascular events, ICU time, mechanical ventilation duration, vasoactive drug use, inflammatory responses, and cardiac cell death. Analysis will consider demographic and clinical factors, with expectations that GPBM will yield superior results compared to NPBMG and similar or better outcomes than CG.

Detailed Description

Anemia increases the risk of postoperative complications and mortality in patients undergoing coronary artery bypass grafting (CABG). In addition, the use of blood transfusions during cardiac surgery is associated with adverse effects and unfavorable outcomes. To reduce the need for transfusions and improve post-operative results, erythropoietin is used as part of Patient Blood Management (PBM). In anemic patients undergoing CABG, the use of Erythropoietin (EPO) can eliminate the need for blood components during and after surgery, as well as reduce adverse events and inflammation. The objectives of the proposed study are to reduce or eliminate the number of transfusions in the intraoperative and postoperative context by means of a Patient Blood Management (PBM) anemia treatment protocol for anemic patients who will undergo Coronary Artery Bypass Graft Surgery (CABG). The proposed study is a prospective, non-controlled interventional study to be carried out with anemic patients awaiting CABG surgery at Hospital São Paulo. There will be three groups of 40 participants each: Control Group (CG) of non-anemic individuals preoperatively; Non- PBM Group (NPBMG) of anemic individuals preoperatively and treated with blood components according to need; PBM Group (GPBM) of anemic individuals preoperatively and treated with EPO. The following parameters will be compared: length of postoperative hospital stay; mortality; postoperative cardiovascular events: clinical stroke, perioperative infarction, surgical reoperation due to bleeding; non- cardiovascular events: surgical site-associated infection and acute renal dysfunction; time in postoperative intensive care; time on mechanical ventilation; need for vasoactive drug use; inflammatory process and intra- and postoperative cardiac cell death. Confounding factors such as demographic and clinical parameters will be included in the analysis. It is expected that the GPBM will obtain the best results in relation to the GNPBM, similar to or better than the CG.

Study Timeline

• Study Start: 2024-06-01
• Study First Submitted: 2024-07-09
• Status Verified: 2024-08
• Study First Submitted QC: 2024-08-04
• Last Update Submitted: 2024-08-04
• Study First Posted: 2024-08-07
• Last Update Posted: 2024-08-07
• Primary Completion: 2025-06-01
• Study Completion: 2026-06-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 120

Inclusion Criteria

• Eletive surgery;
• Only CABG as procedure;
• Off pump CABG candidate.

Exclusion Criteria

• Age > 80 years;
• Chronic dialytic kidney disease;
• Chronic rheumatologic disease;
• Men with Hb levels > 13 g/dl and < 8g/dl;
• Women with Hb levels > 12 g/dl and < 8g/dl;
• Presence of another heart disease requiring surgical intervention;
• Presence of hepatic insufficiency;
• Presence of any implantable electronic cardiac device in any cardiac chambers;
• Pregnancy;
• Diagnosis of malignant neoplasia;
• Thrombophilias;
• Need for Erythropoietin treatment due to any other disease.
• Recent ischemic event (< 3 months).
• Ejection fraction <30%.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Randomized Anemia Group for non-PBM protocol (GNPBM)	blood transfusion	Patients \> 18 years admitted to Hospital São Paulo for Coronary Artery Bypass Grafting (CABG) surgery who are hospitalized in the Cardiovascular Surgery department or another specialty unit and are anemic (Hemoglobin - Hb \< 12g/dl in women and \< 13g/dl in men)
Randomized Anemia Group for PBM protocol (GPBM)	Erythropoietin	Patients \>18 years admitted to Hospital São Paulo for Coronary Artery Bypass Grafting (CABG) surgery who are hospitalized in the Cardiovascular Surgery department or another specialty unit and are anemic (Hb \< 12g/dl in women and \< 13g/dl in men)

Primary Outcome Measures

Name	Time	Method
Mean number of units of Red Blood Cells (RBC)	Until perioperative day 3	Compare the need of blood transfusion in the perioperative period

Secondary Outcome Measures

Name	Time	Method
Perioperative infection	Until perioperative day 3	Anytype
Bleeding	From time of admission on ICU until hour 24th after admission (accountable amount from how many chest tubes the patient was admitted).	Thorax drain tubes bleeding (ml)
Hemoglobin levels	Until perioperative day 3 and at discharge	Accountable in g/dl
Need of Dyalisis (Acute Kidney Disease)	Based on KDIGO classification of Acute Kdney Injury, level III of the classification. (Up to 120 hours from ICU admission, accountable from the time Dyalisis is indicated).	Needing of dyalisis in peoperative period
Inflammatory response	Until perioperative day 3	A total of 25 μl of serum per patient will be used for the detection of the following analytes: IL-1β, IL-6, IL-10, TNF-α, CRP, and NT-ProBNP.
Cardiovascular mortality	From day of the intervention (if intervention group) or from the moment of surgery (if control group) until day of hospital discharge (any cardiovascular reason as main cause of death accountable as in-hospital mortality).)	any cardiovascular reason as main cause of death accountable as in-hospital mortality
Length of ICU stay	From time of admission after surgery to time of clinical conditions of discharge (time of ICU medical discharge, not time of ICU room exit). Up to 240 hours.	Hours
Length of mechanical ventilation	From time of intubation by anesthesia team until time of extubation by ICU team (Up to 240 hours).	Hours
Stroke	Until perioperative day 3	Any level of neurological deficit
Length of hospital stay	From time of ICU medical discharge until time of Hospital discharge (Up to 14 days).	Days
Epigenetics alterations	Until perioperative day 3	. Differentially methylated regions (DMRs) and differentially methylated loci (DMLs) will be considered to determine if these regions are hypermethylated or hypomethylated in the comparison between groups.
Perioperative myocardial infarction	Until perioperative day 3	According to type 5 Myocardial ischemia
All-cause mortality	From day of the intervention (if intervention group) or from the moment of surgery (if control group) until day of hospital discharge (death from any cause accountable as in-hospital mortality).	Death from any cause accountable as in-hospital mortality

Trial Locations

Locations (1)

Leonardo Ohashi; 🇧🇷 São Paulo, SAO Paulo, Brazil