AProtinin Versus Tranexamic Acid in Cardiac Surgery Patients With High-risk for Excessive Bleeding (APACHE)

In this before-after multicenter study the authors tested the hypothesis that the prophylactic use of aprotinin compared to tranexamic acid could reduce the proportion of patients presenting severe perioperative bleeding.

Study Overview

• Status: Completed
• Conditions: Cardiac Surgery; Cardiopulmonary Bypass; High Risk Bleeding
• Intervention / Treatment: Other: standard of care

Detailed Description

Perioperative bleeding remains a real challenge for physicians managing cardiac surgical patients. In patients at high risk for excessive bleeding the prophylactic use of antifibrinolytics may be useful. This study propose to compare the efficacity and innocuity of aprotinin and tranexamic acid to reduce the proportion of patient presenting severe peri-operative bleeding according the Universal Definition of Perioperative Bleeding (UDPB) classification.

• Study Type: Observational
• Enrollment (Actual): 693

Contacts and Locations

Study Locations

• France
  • La Tronche, France, 38700
    • Grenoble University Hospital
  • Lyon, France, 69500
    • Lyon University Hospital
  • Montpellier, France, 34295
    • Montpellier University Hospital
  • Nantes, France, 44093
    • Nantes University Hospital
  • Paris, France, 75877
    • North Val de Seine Paris University Hospital
  • Paris, France, 75908
    • Georges Pompidou European University Hospital
  • Pessac, France, 33604
    • Bordeaux University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

consecutive patients undergoing cardiac surgery with a high risk of hemorrhage who have received a prophylactic infusion of either tranexamic acid or aprotinin and meeting the protocol criteria between july 2017 and october 2020 in seven university hospital centers.

Description

Inclusion Criteria:

patients undergoing cardiac on pump surgery at high risk for bleeding defined by :

• Aorto-coronary bypasses surgery (2 or more) under dual platelet aggregation therapy (Primary or redo)
• Heart transplant (Primary or Redo)
• Infectious endocarditis (Primary or Redo)
• Ascending acute aortic dissection (Primary or Redo)
• Artificial heart / LVAD under CEC (Primary or Redo)
• Combined surgery, Redo
• Ascending aorta surgery, Redo

Exclusion Criteria:

• Off pump cardiac surgery
• Patient not meeting the inclusion criteria
• Patient not receiving antifibrinolytic therapy
• Patient with absolute contraindication to antifibrinolytics,
• Patient refusing to give access to their medical chart,
• Patient not meeting the inclusion criteria
• Patient protected by the law, under guardianship or trusteeship,
• Patient deprived of liberty

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
The aprotinin group,; all patients receiving a first infusion 1M KIU before surgical incision followed by a steady dose of 250 000 KIU/h with an additional dose of 1M KIU added to the cardiopulmonary bypass unit.	Other: standard of care; retrospective study: standard of care
The tranexamic acid group; all patient receiving tranexamic acid following each local center standarded protocol	Other: standard of care; retrospective study: standard of care

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients with severe peri-operative bleeding	Proportion of patients with severe peri-operative bleeding defined by an UDPB (the Universal Definition of Perioperative Bleeding ) classification of 3 and 4.	day 30 after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
distribution of patients by UDPB classification category	proportion of patients with category 0 UDPB.	day 30 after surgery
distribution of patients by UDPB classification category	proportion of patients with category 1 UDPB.	day 30 after surgery
distribution of patients by UDPB classification category	proportion of patients with category 2 UDPB.	day 30 after surgery
distribution of patients by UDPB classification category	proportion of patients with category 3 UDPB.	day 30 after surgery
distribution of patients by UDPB classification category	proportion of patients with category 4 UDPB.	day 30 after surgery
blood loss	post operative chest tube blood loss	24 hours after chest closure
rescue surgery for bleeding	proportion of rescue surgery for bleeding	day 30 after surgery
length of stay	intensive care unit length of stay	through intensive care unit discharge, an average of 30 days
length of stay	hospital length of stay	through hospital discharge, an average of 30 days
KDIGO score greater than or equal to 2	acute kidney injury defined by KDIGO score greater than or equal to 2	day 7 after surgery
mechanical ventilation time	duration of artificial ventilation (hours)	through intensive care unit discharge, an average of 30 days
mechanical ventilation	need to use mechanical ventilation for more than 48 hours	48 hours after surgery
need for transfusion	need for labil blood products and medicinal products derived from blood	up to 48 hours after surgery
need for transfusion	need for labil blood products and medicinal products derived from blood	up to seven day after surgery
need for vasopressors/inotropes	need for use postoperative vasopressors/inotropes for more than 24 hours	beyond 24 hours after surgery
vital status	mortality after surgery	30 days after surgery
new renal replacement therapy	need for renal replacement therapy	up to day 30 after surgery
short term mechanical circulatory support	need for short term mechanical circulatory support (extra corporeal life support, Impella TM pump, intra aortic balloon pump)	up to 30 day after surgery
myocardial infarction	occurrence of myocardial infarction	up to 30 day after surgery
embolic or thrombotic event	occurrence of embolic or thrombotic event	up to 30 day after surgery
stroke	occurrence of stroke	up to 30 day after surgery

Collaborators and Investigators

• Sponsor: University Hospital, Bordeaux

Study record dates

Study Major Dates

• Study Start (Actual): March 31, 2021
• Primary Completion (Actual): August 31, 2021
• Study Completion (Actual): August 31, 2021

Study Registration Dates

• First Submitted: March 10, 2021
• First Submitted That Met QC Criteria: March 15, 2021
• First Posted (Actual): March 18, 2021

Study Record Updates

• Last Update Posted (Actual): March 3, 2022
• Last Update Submitted That Met QC Criteria: March 2, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: cardiac surgery; cardiopulmonary bypass; antifibrinolytics; massive peri-operative bleeding; blood products transfusion
• Additional Relevant MeSH Terms: Pathologic Processes; Hemorrhage
• Other Study ID Numbers: CHUBX 2020/67

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No