Clinical Trial Details
— Status: Not yet recruiting
Administrative data
| NCT number |
NCT06021184 |
| Other study ID # |
ADEFES |
| Secondary ID |
|
| Status |
Not yet recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
November 7, 2023 |
| Est. completion date |
September 30, 2026 |
Study information
| Verified date |
November 2023 |
| Source |
Sakarya University |
| Contact |
Asli Demir, Prof |
| Phone |
+905052491598 |
| Email |
zaslidem[@]yahoo.com |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational [Patient Registry]
|
Clinical Trial Summary
The primary objective of our study is to determine the impact of the ratio of total amount of
fibrinogen transfused over 24 hours to erythrocyte suspension (ADE Fibrinogen/ES) on 30-day
death from any cause OR death from bleeding OR total ES transfusion OR quality of life.
Description:
Massive transfusion, defined as the transfusion of total body blood volume (10 units of
erythrocyte suspension) or more within 24 hours, remains one of the greatest challenges for
the anesthetist. Despite all the medical advances, in cardiac surgery, obstetric surgery,
trauma-orthopedic surgery, major gastrointestinal-genitor-urinary system surgeries, which are
among the major bleeding surgeries, massive hemorrhage continues to be an important mortality
and morbidity factor. In addition to major surgeries with known expected bleeding, massive
transfusion requirement may arise with any undesirable intraoperative event. While the
process is easier to manage with proper preparation and an organized procedure in expected
bleeding, a chaotic response may be encountered in unexpected situations. Special protocols
for each division have been developed by clinicians to manage this critical process, and work
continues on these protocols to improve the outcome.
Massive bleeding management mainly focuses on transfusion and fluid resuscitation. Regardless
of the situation requiring massive transfusion, the goals of treatment in massive bleeding
are to maintain organ perfusion pressure and oxygen delivery, immediately stop bleeding and
coagulopathy. While these goals can be achieved through resuscitation with blood products and
surgical intervention, the triad of hypothermia, acidosis, and coagulopathy that occurs with
the process contributes to increased morbidity and mortality in such scenarios.
The literature on major bleeding from trauma has highlighted some issues contributed to
improved clinical outcomes such as, damage-controlled resuscitation, including timely
initiation of transfusion, early use of clotting factors, minimizing the use of crystalloids.
The landmark PROPPR study found that in the resuscitation of trauma patients, a 1:1:1 ratio
of FFP:platelet:RBC transfusion during massive bleeding resulted in hemostasis in a greater
number of patients (86% versus 78%) compared to a 1:1:2 ratio, additionally, they found fewer
deaths from bleeding within 24 hours (14.6% versus 9.2%). However, no significant difference
was found in 24-hour or 30-day overall mortality. In a systematic review evaluating
retrospective data on transfusions for obstetric bleeding, it was shown that the amount of
FFP administered was greater than the amount of RBC. Since the mortality rate from massive
obstetric hemorrhage is lower than that of traumatic hemorrhage, it is difficult to
prospectively evaluate the effects of massive transfusion. This review recommends a FFP/RBC
ratio of ≥1, with the results of all retrospective studies described on transfusions for
obstetric hemorrhage. Studies in cardiac surgery also suggest that higher rates of FFP/RBC
transfusion are associated with better outcomes in patients with massive bleeding.
In general, the high ratio of transfused FFP to RBC in bleeding surgeries requiring massive
transfusion has been associated with positive results. FFP contains all coagulation factors
and fibrinogen, as well as restoring the volume deficit that occurs with major bleeding,
which reduces the crystalloid requirement and prevents extra dilution of coagulation factors.
Fibrinogen is the clotting factor whose level drops the fastest during bleeding. Fibrinogen
is a unique coagulation building block that plays a role in both primary and secondary
hemostasis. Based on the results of the RETIC trial, the effectiveness of fibrinogen
supplementation in limiting blood loss appears to be strongly dependent on timing of
fibrinogen administration and increasing levels above 200 mg·dL-1. The 5th Edition of the
European Guidelines for the Management of Major Posttraumatic Hemorrhage and Coagulopathy
recommends early and repeated monitoring of fibrinogen concentrations and/or polymerization
and rapid correction of deficiencies. Accordingly, 3-4 g of fibrinogen concentrate or 15-20
units of cryoprecipitate is recommended as an initial dose in massive bleeding. While RETIC
stands out as a randomized controlled prospective study on the role of fibrinogen in massive
transfusion in trauma patients, there are few cardiac and transplantation surgery studies in
various types of research. Regardless of the cause, early restoration of fibrinogen levels in
case of massive bleeding reduces transfusion requirement by preventing ongoing bleeding.
Ideally, fibrinogen concentrate and/or cryoprecipitate are used in fibrinogen replacement,
and FFP is used as a weaker fibrinogen source. During massive transfusion, repeated doses of
FFP/cryoprecipitate/fibrinogen concentrate are used. All of these blood products have
different amounts of fibrinogen content. In many previous studies, the formula for improving
the results was investigated by looking at transfusion rates such as FFP/RBC, RBC/platelet,
FFP/RBC/Platelet. In the light of this information, our hypothesis is that mortality can be
reduced with a high rate of total fibrinogen transfusion from various sources. The primary
aim of our study is to determine the effects of the ratio of total fibrinogen transfused over
24 hours amount to erythrocyte suspension (ACE Fibrinogen/RBC) on 30-day death from any cause
OR death from bleeding OR total ES transfusion OR quality of life.
