Cardiac Surgery: In Vivo Titration of Protamine

NCT ID: NCT00684450

Last Updated: 2011-08-25

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

138 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-06-30

Study Completion Date

2011-06-30

Brief Summary

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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

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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.

Conditions

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Bleeding

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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1

in vivo protamine titration in cardiac surgery. The titration is done during administration of protamine each 3 minutes to reach 2 consecutive ACT defined as 2 similar ACT values, within 10% variability, and ACT ≤ to 160 seconds. .The protamine is stopped when this values are obtain. Follow-up is done 15 minutes and 3 hours post-protamine

Group Type ACTIVE_COMPARATOR

Titration protamine

Intervention Type PROCEDURE

10\. Study group: celite ACT will be performed every 3 minutes during protamine infusion until ACT values suggest reach of a plateau (defined as 2 similar ACT values, within 10% variability, and ACT ≤ to 160 seconds.), time at which infusion will be stopped. 2cc of blood is required per ACT test, for a maximum total of 10cc.

2

standard protamine administration ACT is done during administration of protamine each 3 minutes the values are recorded but the totality of protamine is given. Follow-up is done 15 minutes and 3 hours post-protamine

Group Type ACTIVE_COMPARATOR

Standard administration of protamine

Intervention Type DRUG

1.3 mg of Protamine for 100u héparine

Interventions

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Titration protamine

10\. Study group: celite ACT will be performed every 3 minutes during protamine infusion until ACT values suggest reach of a plateau (defined as 2 similar ACT values, within 10% variability, and ACT ≤ to 160 seconds.), time at which infusion will be stopped. 2cc of blood is required per ACT test, for a maximum total of 10cc.

Intervention Type PROCEDURE

Standard administration of protamine

1.3 mg of Protamine for 100u héparine

Intervention Type DRUG

Other Intervention Names

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Protamine in vivo titration in cardiac surgery

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Organon

INDUSTRY

Sponsor Role collaborator

Montreal Heart Institute

OTHER

Sponsor Role lead

Responsible Party

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Antoine Rochon

M.D. FRCPC

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Antoine G Rochon

Role: PRINCIPAL_INVESTIGATOR

Montreal Heart Institute

Locations

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Montreal Heart Institute

Montreal, Quebec, Canada

Site Status

Countries

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Canada

References

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Young JA, Kisker CT, Doty DB. Adequate anticoagulation during cardiopulmonary bypass determined by activated clotting time and the appearance of fibrin monomer. Ann Thorac Surg. 1978 Sep;26(3):231-40. doi: 10.1016/s0003-4975(10)63676-4.

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Jobes DR, Aitken GL, Shaffer GW. Increased accuracy and precision of heparin and protamine dosing reduces blood loss and transfusion in patients undergoing primary cardiac operations. J Thorac Cardiovasc Surg. 1995 Jul;110(1):36-45. doi: 10.1016/S0022-5223(05)80007-8.

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Other Identifiers

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ICM 07-997

Identifier Type: -

Identifier Source: org_study_id

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