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NCT Number: NCT00684450

Cardiac Surgery: In Vivo Titration of Protamine

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

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Key information

Conditions

Bleeding Hemorrhage Pathologic Processes Pathological Conditions, Signs and Symptoms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Montreal Heart Institute

Montreal, Quebec, H1T 1C8, Canada

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Titration protamine

Procedure
  • 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 names: Protamine in vivo titration in cardiac surgery

Standard administration of protamine

Drug

1.3 mg of Protamine for 100u héparine

Primary outcomes

  1. Effective heparin neutralization (anti-Xa < 0.3 U/ml)

    Time frame: Pre protamine, 15 min post protamine, 3h post protamine

Secondary outcomes

  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

Sponsors and collaborators

Lead sponsor

Montreal Heart Institute

Other

Collaborators

  • Organon

Registry information

Official study title

Cardiac Surgery : In Vivo Titration of Protamine

Acronym: Protamine

Important dates

Study start
2008
Primary completion
2011
Study completion
2011
First posted
May 26, 2008
Registry last updated
Aug 25, 2011

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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