Clinical Trial Comparing Heparin and Protamine Fixed and Titrated Doses in Cardiac Surgery With Cardiopulmonary Bypass
NCT ID: NCT01267487
Last Updated: 2010-12-28
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
COMPLETED
PHASE4
240 participants
INTERVENTIONAL
2009-07-31
2010-11-30
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
These schemes do not take into account the variability inter-patients and can result in overdose or sub-doses of one or both drugs.
The titration schedule of doses of heparin and protamine through the principle of dose-response curve of Bull promotes individualization of dosage according to the response of each patient. This scheme has been associated with an effective reversal of the effect of heparin after CPB and with reduction of post-operatory bleeding and transfusion.
The restoration of a state of anticoagulation by heparin after its reversal by protamine is called "rebound effect". It is a phenomenon explained by the recirculation of heparin stored in the reticulum-endothelial system and connective tissue, or by free residual concentration of heparin after clearance of protamine. This effect may be present for more than 6 hours of post-operatory and may contribute to increase post-operatory bleeding.
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
Secondarily, the investigators compared continuous infusion of small doses of protamine (25mg/hour) and placebo during the first 6 PO hours to neutralize heparin rebound effect. The investigators measured KTTP and fibrinogen levels during the first 24 PO hours and also the difference in blood loss and transfusion requirements between the groups.
The study included patients from 18 to 75 years-old submitted to Cardiac surgeries with Cardiopulmonary Bypass.
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Keywords
Explore important study keywords that can help with search, categorization, and topic discovery.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
RANDOMIZED
FACTORIAL
PREVENTION
TRIPLE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Fixed doses plus PO protamine
Intraoperative fixed dose schemes (as in "fixed doses plus placebo" group) plus continuous infusion of 25mg/hour of protamine during first 6 PO hours
Heparin fixed doses
Fixed doses of 400 units/ kg of patient's body weight before CPB to achieve an ACT \> 480 sec. Supplemental doses of 50mg of heparin if ACT \<480 sec during CPB.
Reversal doses of protamine in a 1:1 ratio (1mg of protamine for every mg of heparin administered), plus 0.8mg/kg of protamine at the end of the surgery.
PO continuous infusion of Protamine
25mg/hour in IV continuous infusion during first 6 PO hours
Titrated doses plus PO protamine
Same as "titrated doses" arm, plus continuous infusion of 25mg/ hour of protamine during first 6 PO hours
PO continuous infusion of Protamine
25mg/hour in IV continuous infusion during first 6 PO hours
Heparin and protamine titration
Titrated doses of heparin during CPB were manually calculated using Bull´s dose-response curve, which was based in periodic assessment of Activated-Coagulation Times (ACT)- baseline ACT, after 2mg/kg of heparin at cannulation and every 15 to 30 minutes during CPB.
Reversal doses of protamine were calculated as a 1:1 ratio of the actual estimated heparin concentration (in mg/kg) at the end of CPB, using the Bull´s dose response curve.
Fixed doses plus placebo
Before CPB, fixed heparin dose of 400 Units per kg of body weight to achieve an Activated Coagulation Time (ACT) \> 480 seconds.
Reversal of heparin after CPB using 1 : 1 ratio (1 mg of protamine for each 100 units (1mg) of heparin), plus 0.8 mg/kg of protamine at the end of the surgery.
Continuous infusion of placebo (saline 0.9%) during the first 6 PO hours.
Heparin fixed doses
Fixed doses of 400 units/ kg of patient's body weight before CPB to achieve an ACT \> 480 sec. Supplemental doses of 50mg of heparin if ACT \<480 sec during CPB.
Reversal doses of protamine in a 1:1 ratio (1mg of protamine for every mg of heparin administered), plus 0.8mg/kg of protamine at the end of the surgery.
Titrated doses plus placebo
Titrated doses of heparin before and during CPB and reversal with protamine after CPB calculated by the construction of individualized Bull's dose-response curve.
Continuous infusion of placebo (saline 0.9%) during first 6 PO hours.
Heparin and protamine titration
Titrated doses of heparin during CPB were manually calculated using Bull´s dose-response curve, which was based in periodic assessment of Activated-Coagulation Times (ACT)- baseline ACT, after 2mg/kg of heparin at cannulation and every 15 to 30 minutes during CPB.
Reversal doses of protamine were calculated as a 1:1 ratio of the actual estimated heparin concentration (in mg/kg) at the end of CPB, using the Bull´s dose response curve.
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Heparin fixed doses
Fixed doses of 400 units/ kg of patient's body weight before CPB to achieve an ACT \> 480 sec. Supplemental doses of 50mg of heparin if ACT \<480 sec during CPB.
Reversal doses of protamine in a 1:1 ratio (1mg of protamine for every mg of heparin administered), plus 0.8mg/kg of protamine at the end of the surgery.
PO continuous infusion of Protamine
25mg/hour in IV continuous infusion during first 6 PO hours
Heparin and protamine titration
Titrated doses of heparin during CPB were manually calculated using Bull´s dose-response curve, which was based in periodic assessment of Activated-Coagulation Times (ACT)- baseline ACT, after 2mg/kg of heparin at cannulation and every 15 to 30 minutes during CPB.
Reversal doses of protamine were calculated as a 1:1 ratio of the actual estimated heparin concentration (in mg/kg) at the end of CPB, using the Bull´s dose response curve.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
* Age 18 to 75 years-old
Exclusion Criteria
* INR \> 1,3
* Platelets \< 100,000
* Altered KTTP
* Receiving Non-fractioned Heparin or Low-Molecular Weight Heparin
* Renal Insufficiency or Creatinine \> 2,0
* Liver Failure or altered ALT/AST
* Von Willebrands'disease, Haemophilia, sepsis
* Use in the past 7 days of antiplatelet-therapy(Ticlopidine or Clopidogrel)
18 Years
75 Years
ALL
No
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
Instituto de Cardiologia do Rio Grande do Sul
OTHER
Fundação Universitária de Cardiologia (University Foundation of Cardiology)
UNKNOWN
SANE-Society of Anesthesiology
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
CET/ SBA - SANE
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
Maria B Chuquer, M. D.
Role: PRINCIPAL_INVESTIGATOR
SANE-Society of Anesthesiology
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Instituto de Cardiologia do Rio Grande do Sul
Porto Alegre, Rio Grande do Sul, Brazil
Countries
Review the countries where the study has at least one active or historical site.
References
Explore related publications, articles, or registry entries linked to this study.
Shore-Lesserson L, Reich DL, DePerio M. Heparin and protamine titration do not improve haemostasis in cardiac surgical patients. Can J Anaesth. 1998 Jan;45(1):10-8. doi: 10.1007/BF03011985.
Teoh KH, Young E, Blackall MH, Roberts RS, Hirsh J. Can extra protamine eliminate heparin rebound following cardiopulmonary bypass surgery? J Thorac Cardiovasc Surg. 2004 Aug;128(2):211-9. doi: 10.1016/j.jtcvs.2003.12.023.
Pappalardo F, Franco A, Crescenzi G, De Simone F, Torracca L, Zangrillo A. Anticoagulation management in patients undergoing open heart surgery by activated clotting time and whole blood heparin concentration. Perfusion. 2006 Dec;21(5):285-90. doi: 10.1177/0267659106074770.
Griffin MJ, Rinder HM, Smith BR, Tracey JB, Kriz NS, Li CK, Rinder CS. The effects of heparin, protamine, and heparin/protamine reversal on platelet function under conditions of arterial shear stress. Anesth Analg. 2001 Jul;93(1):20-7. doi: 10.1097/00000539-200107000-00005.
Bull BS, Huse WM, Brauer FS, Korpman RA. Heparin therapy during extracorporeal circulation. II. The use of a dose-response curve to individualize heparin and protamine dosage. J Thorac Cardiovasc Surg. 1975 May;69(5):685-9.
Society of Thoracic Surgeons Blood Conservation Guideline Task Force; Ferraris VA, Ferraris SP, Saha SP, Hessel EA 2nd, Haan CK, Royston BD, Bridges CR, Higgins RS, Despotis G, Brown JR; Society of Cardiovascular Anesthesiologists Special Task Force on Blood Transfusion; Spiess BD, Shore-Lesserson L, Stafford-Smith M, Mazer CD, Bennett-Guerrero E, Hill SE, Body S. Perioperative blood transfusion and blood conservation in cardiac surgery: the Society of Thoracic Surgeons and The Society of Cardiovascular Anesthesiologists clinical practice guideline. Ann Thorac Surg. 2007 May;83(5 Suppl):S27-86. doi: 10.1016/j.athoracsur.2007.02.099.
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.
Levy JH, Tanaka KA. Anticoagulation and reversal paradigms: is too much of a good thing bad? Anesth Analg. 2009 Mar;108(3):692-4. doi: 10.1213/ane.0b013e31819614dd. No abstract available.
Despotis GJ, Joist JH, Hogue CW Jr, Alsoufiev A, Kater K, Goodnough LT, Santoro SA, Spitznagel E, Rosenblum M, Lappas DG. The impact of heparin concentration and activated clotting time monitoring on blood conservation. A prospective, randomized evaluation in patients undergoing cardiac operation. J Thorac Cardiovasc Surg. 1995 Jul;110(1):46-54. doi: 10.1016/S0022-5223(05)80008-X.
Lobato RL, Despotis GJ, Levy JH, Shore-Lesserson LJ, Carlson MO, Bennett-Guerrero E. Anticoagulation management during cardiopulmonary bypass: a survey of 54 North American institutions. J Thorac Cardiovasc Surg. 2010 Jun;139(6):1665-6. doi: 10.1016/j.jtcvs.2010.02.038. Epub 2010 Mar 19. No abstract available.
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
UP 4316/09
Identifier Type: -
Identifier Source: org_study_id