Clinical trial NCT00684450: Cardiac Surgery: In Vivo Titration of Protamine
Official title: Cardiac Surgery : In Vivo Titration of Protamine
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Bleeding
Keywords: titration of protamine
exact dose
protamine
neutralize heparin
Lead sponsor: Montreal Heart Institute
Sponsor class: OTHER
Collaborators: name: Organon
First posted: 2008-05-26
Enrollment: 138
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Safe use of cardiopulmonary bypass (CPB) requires massive doses of intravenous unfractionated heparin. At end-CPB, residual heparin is neutralized with intravenous injection of protamine sulfate. This prospective, randomized, controlled study will be conducted in 82 voluntary subjects admitted for elective, first intention, cardiac surgery requiring cardiopulmonary bypass. Each will be randomly assigned to one of two groups. The control group will be submitted to a standard protamine infusion of 1.3mg :100U of the total heparin dose given during bypass. The test group will receive an infusion of protamine (over 15 minutes) until activated clotting time (ACT) values (determined every 3 minutes) depict a plateau, sign that the optimal protamine to heparin ratio has been attained. The investigators hypothesize this new in vivo titration method to be as efficient as the standard protocol (adequacy of heparin neutralization, % heparin rebound, bleeding, and transfusion), and potentially safer by its ability to prevent protamine overdose and its deleterious impact on platelet function.15

Principal Objective

Evaluate a new in vivo method of titration of protamine sulfate.

Secondary Objective

Evaluate the impact of this method on the adequacy of heparin neutralization by measuring:

1. platelet count
2. postoperative bleeding
3. transfusion exposure a
4. incidence of heparin rebound

Detailed description: Protamine sulfate is administered to reverse the anticoagulant effects of heparin upon completion of cardiopulmonary bypass (CPB). In most cases, protamine is given in amounts sufficient to neutralize the total dose of heparin.9 This dose is usually calculated with a ratio of 1.3mg protamine for every 100U heparin given.10 In the literature, reported doses of intraoperatively administered protamine range from 0 to 8mg per 100U of heparin. Given in excess, protamine can, in addition to complement activation and hemodynamic instability,11 induce platelet dysfunctions.12-16 The latter significantly increases both the cost and morbidity of cardiac interventions as it is one of the main causes of postoperative bleeding. The optimal protamine/heparin ratio is difficult to individualize for each patient because of the great interpatient variability in heparin's metabolism4-7 and of the absence of correlation between ACT and heparin's plasma concentration.8 Consumption of heparin may vary from 0.01 to 3.86U/Kg per minute during CPB.30 The exact concentration of remaining circulating heparin at the end of bypass is not easily obtained.

Eligibility criteria: Inclusion Criteria:

* First intention, elective, cardiac surgery: either Coronary Artery Bypass Graft (CABG)or valve repair/replacement.
* Patients on preoperative aspirin, clopidogrel or heparin will be included.

Exclusion Criteria:

* Combination of CABG and valve surgery
* Second intention cardiac surgery
* ASA 5 patients
* Pre-existing hemostatic disorder (as evidenced by history)
* Pregnancy
* PLavix \< 5 days before de surgery

Primary outcomes:
measure: Effective heparin neutralization (anti-Xa < 0.3 U/ml)
timeFrame: Pre protamine, 15 min post protamine, 3h post protamine
Secondary outcomes:
measure: Frequency of heparin rebound
timeFrame: 15 min post protamine and 3 hours post Protamine
measure: Blood losses after surgery and transfusion requirements
timeFrame: discharge
measure: Preservation of the platelet count
timeFrame: Pre operate, Pré Protamine, 15 min post Protamine, 3 hours post Protamine
Other outcomes:
Locations:
city: Montreal
country: Canada
facility: Montreal Heart Institute
state: Quebec
Study officials:
affiliation: Montreal Heart Institute
name: Antoine G Rochon
role: PRINCIPAL_INVESTIGATOR
References:
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