Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT06154018 |
| Other study ID # |
179/23-2-2023 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
March 18, 2023 |
| Est. completion date |
April 30, 2024 |
Study information
| Verified date |
May 2024 |
| Source |
University of Ioannina |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Protamine is routinely used as a heparin reversal agent in cardiac surgery. However, its use
may be associated with adverse events, while protamine excess may have additional
anti-coagulant affect. Although guidelines advise towards a diminished reversal ratio,
clinical practice remain heterogenic. The purpose of this study is to compare two different
reversal ratios (0.6:1 και 0.8:1) of total heparin regarding the Activated Clotting Time
(ACT), viscoelastic assays (Clot-Pro) and clinical hemorrhage.
A baseline ACT value and Clot Pro tests will be obtained prior to the operation start. After
the initial reversal, ACT, Clot Pro tests will be conducted again. Coagulation factors are
administrated according to Clot Pro results, and in case of ongoing clinical hemorrhage and
any indication of heparin excess in the measured values, another 25mg of protamine is
administrated, while tests are repeated.
Description:
Protamine is routinely administered as a heparin-reversal factor in cardiac surgery. However,
protamine is associated with specific adverse events, while it has additional anticoagulant
effect while in excess. The literature supports that a reversal ratio lower than 1mg:100 IU
(1:1) of heparin is safe and effective. According to recent studies, a ratio equal to 0.84:1
of initial or 0,6 of total heparin is safe and effective in cardiac surgery. Even lower
ratios (<0,5:1) have been studied with positive outcomes.
The aim of this study is to evaluate the effectiveness of heparin reversal with two different
protamin ratios (0,6:1 και 0,8:1) regarding the Activated Clotting Time (ACT), viscoelastic
tests (Clot-Pro) and clinical hemorrhage.
Methods Perioperative management will follow standard department practice. The patients will
be randomized to receive an initial dosage of protamine in a ratio 0.8 or 0.6 to 1 of the
total heparin post cardiopulmonary by-pass disengagement. ACT and Clot Pro tests (IN, HI, EX
and FIB-test) will run. In case of ongoing clinical hemorrhage, coagulation factors will
administrated according to Clot Pro results, and in case of persistent clinical hemorrhage
and any indication of heparin excess in the measured values, another 25mg of protamine will
be administrated, while tests will be repeated. All patients will sign an informed consent
prior to their inclusion in the study.
Data collection During pre-operative evaluation, age, weight, height, sex, BSA, ASA
classification, Euroscore II, medication and co-morbidities will be documented.
Intraoperatively, anesthesia, cardiopulmonary bypass and aortic cross clamping time will be
documented, as well as drugs administered and related adverse events.
Methods Induction in anesthesia will follow standard practice using fentanyl, prorofol and
rocuronium. Maintenance will be achieved with sevoflurane. After induction in anesthesia and
before heparin administration ACT and viscoelastic (Clot Pro) test results will be run using
blood withdrawn form the patient's arterial line.
After disengagement from cardiopulmonary by-pass, protamine will be administered in a dosage
according to randomization in a total volume of 60ml (diluted with normal saline). Five
minutes later, another blood sample will be withdrawn form the patient's arterial line and
ACT and Clot Pro tests (i.e. EX-, FIB-, IN- and HI- TEST) will be run again. In case of
ongoing clinical bleeding, clotting factors will be administered according to the Clot PRo
tests results. If bleeding persists, and there is and indication of either the ACT value or
the IN to HI test ratio that there is heparin excess, another 25mg of protamine will be
administered and ACT and Clot Pro tests will be repeated. The step can be repeated as many
times as there is an indication of protamine excess and ongoing clinical bleeding.
Transfusion and clotting products requirements will be recorded. Finally, the patients will
be monitored for mechanical ventilation duration, transfusion requirements during ICU stay,
postoperative bleeding and adverse events related to surgery and anesthesia for 48 hours
postoperatively. A secondary analysis will depict the changes in thromboelastography before
and after cardiopulmonary bypass as depicted in the ClotPro tests.
Purpose of the study The present study aims to evaluate two different ratios of heparin
reversal (0.6 and 0.8 of total heparin)with protamine after the end of cardiopulmonary by
pass in cardiac surgery patients. It is a prospective, randomized, comparative study of
clinical hemorrhage, Activated Clotting Time (ACT) and viscoelastic tests using the
ClotPro.Secondary endpoints are transfusion requirements, clotting factors administration,
postoperative bleeding, mechanical ventilation duration and ICU length of stay.
