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Trial record 3 of 200 for:    Protamine

Cardiac Surgery: In Vivo Titration of Protamine (Protamine)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00684450
Recruitment Status : Completed
First Posted : May 26, 2008
Last Update Posted : August 25, 2011
Information provided by (Responsible Party):
Antoine Rochon, Montreal Heart Institute

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

Condition or disease Intervention/treatment Phase
Bleeding Procedure: Titration protamine Drug: Standard administration of protamine Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 138 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Cardiac Surgery : In Vivo Titration of Protamine
Study Start Date : June 2008
Actual Primary Completion Date : June 2011
Actual Study Completion Date : June 2011

Resource links provided by the National Library of Medicine

Drug Information available for: Protamine

Arm Intervention/treatment
Active Comparator: 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
Procedure: 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.
Other Name: Protamine in vivo titration in cardiac surgery

Active Comparator: 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
Drug: Standard administration of protamine
1.3 mg of Protamine for 100u héparine

Primary Outcome Measures :
  1. Effective heparin neutralization (anti-Xa < 0.3 U/ml) [ Time Frame: Pre protamine, 15 min post protamine, 3h post protamine ]

Secondary Outcome Measures :
  1. Frequency of heparin rebound [ Time Frame: 15 min post protamine and 3 hours post Protamine ]
  2. Blood losses after surgery and transfusion requirements [ Time Frame: discharge ]
  3. Preservation of the platelet count [ Time Frame: Pre operate, Pré Protamine, 15 min post Protamine, 3 hours post Protamine ]

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00684450

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Canada, Quebec
Montreal Heart Institute
Montreal, Quebec, Canada, H1T 1C8
Sponsors and Collaborators
Montreal Heart Institute
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Principal Investigator: Antoine G Rochon Montreal Heart Institute

Hattersley PG. ACT in the whole blood. JAMA 1966;196:150-154.

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Responsible Party: Antoine Rochon, M.D. FRCPC, Montreal Heart Institute Identifier: NCT00684450     History of Changes
Other Study ID Numbers: ICM 07-997
First Posted: May 26, 2008    Key Record Dates
Last Update Posted: August 25, 2011
Last Verified: August 2011
Keywords provided by Antoine Rochon, Montreal Heart Institute:
titration of protamine
exact dose
neutralize heparin
Additional relevant MeSH terms:
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Pathologic Processes
Heparin Antagonists
Molecular Mechanisms of Pharmacological Action