Protamine in Cardiac Surgery and Haemostasis (PROTT)

This study has been completed.
Information provided by (Responsible Party):
Andreas Koster, Heart and Diabetes Center North-Rhine Westfalia Identifier:
First received: May 29, 2012
Last updated: November 18, 2015
Last verified: November 2015
Protamine is used after Cardiopulmonary Bypass (CPB) to reverse the anticoagulant effects of heparin and restore coagulation. Convincing evidence from in-vitro and in-vivo studies suggest that an overdose of protamine has anticoagulant effects which might lead to bleeding complications. Heparin levels usually decrease during cardiac surgery with CPB. Therefore, a protamine regimen based on the initial heparin dose before CPB might lead to overdose of protamine. In contrast, a protamine regimen based on the actual heparin concentration may avoid this condition. The investigators compare both regimens of protamine dosing in patients undergoing complex surgery with CPB and assess its effect on the amount of protamine given, markers of the coagulation system, utilization of blood products and perioperative blood loss.


Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: The Effects of Heparin Level Based Versus Weight Based Protamine Dosing on Protamine Demand, Markers of Haemostasis, Blood Product Utilization and Perioperative Blood Loss in Patients Undergoing Extended Cardiac Surgery Cardiac Surgery

Resource links provided by NLM:

Further study details as provided by Heart and Diabetes Center North-Rhine Westfalia:

Primary Outcome Measures:
  • INTEM HEPTEM and FIBTEM Test of the ROTEM Coagulation Analyzer [ Time Frame: Tests will be measured 15 minutes after Protamine infusion ] [ Designated as safety issue: No ]
    The Intem test of the ROTEM analyzer evaluates the response of the heamostatic system to activation of the intrinsic coagulation system. The following parameters of the INTEM test will be analyzed. CT [seconds](coagulation time), CFT [seconds] (clot formation time) and the CT [seconds] of the HEPTEM test which is non sensitive for residual heparine.

  • Rotem MCF Fibtem and MCF Intem [ Time Frame: 15 Minutes after protamine infusion ] [ Designated as safety issue: No ]
    The following parameters of the INTEM test will be analyzed: MCF [mm] (maximum clot firmness) which correlates with the platelet count. Furthermore, the MCF [mm] of the FIBTEM test will be analyzed, which correlates with the fibrinogen concentration.

Secondary Outcome Measures:
  • Transfusion of Blood Products and Coagulation Factors [ Time Frame: From protamine administration until 12 h after surgery ] [ Designated as safety issue: No ]
    The transfusion of blood products and coagulation factors will be assesed from protamine administration until 12 hours postoperatively .

  • 12 h Postoperative Blood Loss [ Time Frame: 15 min after protamine administration until 12 hours postoperatively ] [ Designated as safety issue: No ]
    The intra and postoperative blood loss from the time point of protamine administration until 12 hours postoperatively will be analyzed.

Enrollment: 30
Study Start Date: January 2011
Study Completion Date: March 2012
Primary Completion Date: March 2012 (Final data collection date for primary outcome measure)
Weight based protamine group
In this group the dose of protamine is calculated by the weight of the patients (400 IU/kg)
Heparin level based protamine group
In this group the protamine dose will be calculated 1:1 according to the heparin level measured after termination of cardiopulmonary bypass.

  Show Detailed Description


Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Patients undergoing complex cardiac surgery using cardiopulmonary bypass with mitral valve repair/replacement and 2-4 coronary artery bypass grafting including the left thoracic artery

Inclusion Criteria:

  • Primary surgery
  • Preoperative hemoglobin value < 12 g/l
  • Preoperative platelet count < 200 c/µl
  • Patients with a body weight < 50 kg
  • No known defect of the coagulation system
  • Normal pre-operative ROTEM values of the INTEM and FIBTEM
  • Patients with unimpaired renal function (creatinine clearance < 30 ml/kg/min)

Exclusion Criteria:

  • <18 years
  • No informed consent
  • Re-do surgery
  • Known defect of the coagulation system
  • Renal impairment
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01608971

Heart & Diabetes Center NRW
Bad Oeynhausen, North Rhine-Westphalia, Germany, 32545
Sponsors and Collaborators
Heart and Diabetes Center North-Rhine Westfalia
Principal Investigator: Andreas Koster, MD Heart & Diabetes Center NRW, Ruhr University Bochum, 32545 Bad Oeynhausen, Germany
  More Information

Responsible Party: Andreas Koster, Senior anaestetist, Heart and Diabetes Center North-Rhine Westfalia Identifier: NCT01608971     History of Changes
Other Study ID Numbers: 007
Study First Received: May 29, 2012
Results First Received: March 17, 2015
Last Updated: November 18, 2015
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Heart and Diabetes Center North-Rhine Westfalia:
heparin level
cardiac surgery
Patients undergoing cardiac surgery

Additional relevant MeSH terms:
Cardiovascular Agents
Fibrin Modulating Agents
Fibrinolytic Agents
Hematologic Agents
Heparin Antagonists
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses processed this record on November 27, 2015