"ADE Fibrinogen/RBC" Ratio on Mortality and Outcome in Massive Transfusion Patients

NCT06021184 | Recruiting DMC

• 1 other identifier: ADEFES
• Study Type: observational
• Target: 1,679
• Locations: 1 country
• Sites: 1

Brief Summary

Our study focuses on the transfusion of blood and blood products in cases of major bleeding, including massive transfusion scenarios where repeated doses of packed red blood cells (PRBC), fresh frozen plasma (FFP), cryoprecipitate, and fibrinogen concentrate are administered. Each of these blood products contains varying amounts of fibrinogen. Previous research has explored formulas to enhance outcomes by examining transfusion ratios such as FFP/ES, ES/platelet, and FFP/ES/platelet. Building on this, our hypothesis is that increasing the total fibrinogen content provided within a short period of time from the beginning of major bleeding reduces mortality and morbidity. To standardize the fibrinogen amounts from different sources under a single pool, we developed a formula that equalizes the fibrinogen content across these products. Using the below formula, we aim to investigate the impact of the overall ADEF/ES ratio on mortality and functional outcomes in major bleeding. Approximate Dose-Equivalent for Fibrinogen (ADE): 1 gram of fibrinogen = 5 units of cryoprecipitate = 1.5 units of FFP, evaluated as total grams of fibrinogen.

Conditions

Massive Transfusion; Bleeding During/following Surgery

Keywords

massive transfusion; fibrinogen; fresh frozen plasma; red blood cell; cryoprecipitate; erythrocyte suspension; bleeding surgeries

Outcome Measures

Primary Outcomes (1)

• Composite score of any one of the following events occurring 30 days within the beginning of transfusion:

  (1) 30-day all-cause mortality, (2) bleeding-specific mortality, (3) the Katz index of independence in activities of daily living. To determine the effect of the ratio of total fibrinogen to erythrocyte suspension (ADE Fibrinogen/ES) transfused at 24 hours on the composite outcome, which includes 30-day all-cause mortality, bleeding-specific mortality, and the Katz index of independence in activities of daily living (scored 0, 1, 2) i.e. extremely dependent to highly dependent).

  From enrollment (beginning of transfusion for surgical bleeding) to the end of 30 days

Secondary Outcomes (20)

• Postoperative 24-hour all-cause and bleeding specific mortality

  From enrollment (beginning of transfusion for surgical bleeding) to the end of 24 hour

• Postoperative 3-month all-cause and bleeding specific mortality

  From enrollment (beginning of transfusion for surgical bleeding) to the end of 3 month

• Morbidity(>90 day)

  90 days after registration (from the start of transfusion for surgical bleeding)

• Mortality predictors

  90 days after registration (from the start of transfusion for surgical bleeding)

• Cardiac complications

  90 days after registration (from the start of transfusion for surgical bleeding)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Adult patients who received at least 4 unite RBC transfusion and a fibrinogen containing product

You may qualify if:

• Age ≥ 18
• Surgical patients who received ''Transfusion of ≥ 4 U ESs and at least one fibrinogen-containing product (FFP, fibrinogen concentrate, cryoprecipitate) within 24 hours''
• Elective or emergency surgical procedures with major bleeding. Major bleeding surgeries; cardiovascular and thoracic surgery, obstetric-gynecologic surgery, orthopedics/trauma surgery, neurosurgery, transplantation and major ENT-GIS-GUS surgeries.
• Informed Consent
• Undergoing surgery within 24 hours of massive blood transfusion

You may not qualify if:

• Death before massive transfusion
• Death during massive transfusion
• Patients whose perioperative bleeding and transfusion data cannot be accessed in detail
• Patients with missing data or non-compliance with study protocol
• Patients who have zero ADEF/ES ratio

Sponsors & Collaborators

• Ankara City Hospital Bilkent: lead
• Istanbul University: collaborator
• Ondokuz Mayıs University: collaborator
• Dr Abdurrahman Yurtaslan Ankara Oncology Training and Research Hospital: collaborator
• Kanuni Sultan Suleyman Training and Research Hospital: collaborator
• Saglik Bilimleri Universitesi: collaborator
• Sakarya University: collaborator
• Acibadem Atakent University Hospital: collaborator
• Bursa Yuksek Ihtisas Training and Research Hospital: collaborator

Study Sites (1)

Ankara Bilkent city hospital

Ankara, çankaya, 06800, Turkey (Türkiye)

RECRUITING

Related Publications (1)

• Demir ZA, Kavak Akelma F, Akca O, Koltka K, Dincer B, Kocyigit M, Tuna AT, Sayin J, Yildirim Ar A, Kuvaki B, Aykut A, Sahin AS, Aydin Guzey N; ADEFES Investigators. Impact of fibrinogen-to-erythrocyte suspension ratio on mortality and functional outcomes in major perioperative bleeding (Approximate Dose-Equivalent of Fibrinogen-to-Erythrocyte Suspension (ADEFES) study): protocol for a prospective observational study. BMJ Open. 2025 Sep 16;15(9):e099044. doi: 10.1136/bmjopen-2025-099044.

  PMID: 40962355 DERIVED

Study Officials

• Kemalettin Koltka, Prof

  Istanbul University

  STUDY CHAIR

Central Study Contacts

Zeliha Aslı Demir, Prof

CONTACT

+905052491598; zaslidem@yahoo.com

Fatma Kavak Akelma, Assoc Prof

CONTACT

+905327079113; fakelma@gmail.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: OTHER
• Target Duration: 3 Months
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 28, 2023
• First Posted: September 1, 2023
• Study Start: November 7, 2023
• Primary Completion: October 30, 2025
• Study Completion (Estimated): September 30, 2026
• Last Updated: December 12, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

TU (1)