|- candidate number||13142|
|- NTR Number||NTR3528|
|- ISRCTN||ISRCTN wordt niet meer aangevraagd.|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||13-jul-2012|
|- Secondary IDs||CCH2012-02 / NL40764.029.12; VU / ABR|
|- Public Title||De effecten van verschillende doseringsverhoudingen van middelen die de stolling remmen of activeren op bloedverlies tijdens hartchirurgie. |
|- Scientific Title||The effect of a high and low protamine-to-heparin dosing on perioperative hemostasis: A randomized clinical trial.|
|- ACRONYM||Ratio-PRO study|
|- hypothesis||It is hypothesized that a low protamine-to-heparin ratio leads to improved hemostasis after cardiac surgery with cardiopulmonary bypass as compared to a high ratio as measured by rotational thromboelastometry, and reduces postoperative blood loss and blood product transfusion.|
|- Healt Condition(s) or Problem(s) studied||Cardiac surgery, Coronary Artery Bypass Grafting (CABG), Cardiopulmonary Bypass (CPB)|
|- Inclusion criteria||1. Patients undergoing coronary artery bypass graft (CABG) surgery;|
2. Age 18-85 years;
3. Informed consent.
|- Exclusion criteria||1. Re-operations;|
2. Emergency operation;
3. Patients with a history of hematologic disorders or renal replacement therapy;
4. Patients with a body mass index (BMI) below 18 kg/m2 or above 35 kg/m2.
|- mec approval received||no|
|- multicenter trial||yes|
|- Type||2 or more arms, randomized|
|- planned startdate ||1-sep-2012|
|- planned closingdate||31-aug-2014|
|- Target number of participants||98|
|- Interventions||Prior to and during cardiopulmonary bypass heparin is transfused in order to avoid massive coagulation activation by the contact surface of the heart-lung-machine. This administration is based on the bodyweight and activated clotting time (ACT) of the patient after heparin administration. Protamine is transfused after cardiopulmonary bypass in order to inactivate the heparin and thereby reactivate clotting. It does so by forming a 1:1 salt complex with heparin. The protamine dosing is according to current guidelines done in a 1.0-1.3 : 1.0 ratio with heparin. However it is suggested that due to the degrading and loss of heparin during surgery using this approach protamine is overdosed when transfused. Since protamine itself has anticoagulant properties this would deteriorate postoperative hemostasis.
Therefore this study investigates if the use off a lower dosing ratio (0.8) is superior as compared to the general protamine dosing, a high protamine-to-heparin dosing ratio (1.3).
|- Primary outcome||Postoperative 24-hour blood loss assessed by wound drainage.|
|- Secondary outcome||1. Hemostatic monitoring;|
2. ROTEM: Intem, Heptem, Extem, Fibtem;
A. Clotting Time (CT);
B. Maximum Clot Firmness (MCF);
C. Clot Formation Time (CFT).
3. Classical coagulation tests:
4. Activated Clotting Time (ACT);
6. Heparin concentration;
7. Antithrombin III;
8. Thrombin generation;
9. Patient demographics;
10. Surgery time, CPB time, cross-clamp time;
11. Transfusion of blood products.
|- Timepoints||At three time points during cardiac surgery (before cardiopulmonary bypass, and at 3 and 30 minutes following protamine administration, blood samples are drawn for further analysis. Postoperative hemostasis monitoring continues until 24 hours following surgery.|
|- Trial web site||N/A|
|- CONTACT FOR PUBLIC QUERIES||Drs. A.B.A. Vonk|
|- CONTACT for SCIENTIFIC QUERIES||Dr. Christa Boer|
|- Sponsor/Initiator ||VU University Medical Center|
(Source(s) of Monetary or Material Support)
|VU University Medical Center|
|- Brief summary||Prior to, and during cardiopulmonary bypass, heparin is transfused in order to avoid massive coagulation activation by the contact surface of the heart-lung-machine. Heparin dosing is commonly based on bodyweight and activated clotting time (ACT). After cardiopulmonary bypass, protamine is transfused to neutralize heparin, thereby reactivating the clotting cascade. Protamine forms a 1:1 salt complex with heparin, but may exhibit an intrinsic anticoagulant activity after overdosing.
According to current guidelines, protamine dosing is performed in a 1.0-1.3:1.0 ratio with heparin. However, our own observations and several literature reports suggest that, due to the degrading and loss of heparin during surgery, protamine is usually overdosed. The consequent overdosing of protamine might deteriorate postoperative hemostasis. The present study investigates whether the use of a lower dosing protamine-to-heparin dosing ratio (0.8) is superior as compared to a high protamine-to-heparin dosing ratio (1.3) with respect to postoperative hemostasis, blood loss and transfusion.|
|- Main changes (audit trail)|
|- RECORD||13-jul-2012 - 5-aug-2012|