Comparative Study of Two Brands of Heparin Already on the Market

Do Different Heparin Brands Influence Bleeding in Coronary Surgery

Two heparin brands have been in the market in Canada for several years. Heparin Leo from Leo Pharma and Hepalean from Organon. The former is standardized by B.P (British pharmacopeia) while the latter is standardized by U.S.P (United states pharmacopeia). Previous studies have shown Heparin Leo to have roughly a 10% less efficacy then Hepalean. It has also been demonstrated that more protamine is required to reverse Heparin Leo. It is the investigators' intention to study the post-operative effects of the two brands of heparin and whether one of the two causes less bleeding after bypass surgery.

Study Overview

• Status: Completed
• Conditions: Coronary Artery Bypass Grafting
• Intervention / Treatment: Drug: Heparin Leo and Hepalean

Detailed Description

The study protocol attempts not to change the normal protocol for cardiac surgery too much.

The two different brands of heparin-Heparin Leo (Leo pharma) and Hepalean (Organon) are randomized by the float perfusionist using the program research randomizer.A 50 ml syringe is loaded with heparin for the Anesthesiologist and labelled. A 20 ml syringe is loaded with heparin and thenn labelled. It is a double blinded trial with the surgeon and anesthetist not knowing which brand heparin is being used. All cases are isolated Coronary Artery Bypass Grafting (C.A.B.G) with no concomittant conditions. The following are the patients excluded from the trial

1. RE-DO
2. COMBINATION PROCEDURE
3. VALVE REPAIR/REPLACEMENT
4. IABP-PRE/INTRA//POST-OP
5. CELL SAVER INTRA-OP
6. ANEMIA (70 g/L)/BLEEDING DISORDER eg:Jehovah's witness,hemophilia etc.
7. USE OF APROTININ
8. SMALL ADULT < 50 KG
9. AORTIC SURGERY WITH/WITHOUT CIRC ARREST
10. EMERGENT PATIENT WITH HEART FAILURE

Heparin will be administered in the trial to elevate the A.C.T-Activated clotting time to 480 s and above and the heparin level to 300u/Kg to intiate cardio-pulmonary bypass (C.P.B). Additional heparin will be given to maintain the above-mentioned levels.

The following data will be studied

• BSA
• Height
• Weight
• Diagnosis
• Procedure
• Surgeon
• Anesthetist
• Perfusionist

Pre pump Hb Pump Hb Post pump Hb

Pre pump ACT Pump ACT Post pump ACT

Projected heparin conc. Slope Protocol heparin conc Heparin time CPB time X-clamp time Heparin (initial dose) Extra heparin on pump Prime Volume RAP Volume Pump balance ml Urine output ml Average temp on CPB Phenylephrine Amt Levofed amt Creatinine AST Calculated protamine dose at the end of the case Extra protamine given Total protamine CBC after pump Total chest tube drainage in OR ml Total patient in OR time

Pre pump Post Pump Platelet INR PTT PT

Date Time NA Plavix stopped ASA stopped Heparin stopped Coumadin stopped

FFP given Total packed cells given Total platelets given Other factors given Other blood product given Ca2+ given DDAVP given

Post-op 6 hrs 12 hrs 24 hrs Chest tube drainage (ml) Chest tube removed time Hct Platelet INR PTT

ADDITIONS Packed cells Cryo Platelets Other blood product / factors

Chest reopening Yes No The reason if yes Patient transfer date- Time

Overall we are going to look at whether their is any impact on post-operative bleeding,hospital and ICU stay.

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Newmarket, Ontario, Canada, L3Y 2P9
      • Southlake Regional Health Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Isolated Coronary Artery Bypass Surgery
• Normal Hematocrit
• Normal Creatinine
• Normal Liver function

Exclusion Criteria:

• Re-do
• Combination procedure
• Valve repair/replacement
• IABP-pre/Intra/Post-op
• Cell saver intra-op
• Anemia (70 g/L)/Bleeding disorder, e.g.,: Jehovah's witness, hemophilia etc.
• Use of aprotinin
• Small adult < 50 kg
• Aortic surgery with/without circ. arrest
• Emergent patient with heart failure

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Heparin; Compare two market brands of Heparin	Drug: Heparin Leo and Hepalean; Dosage based on Heparin does response curve obtained from the Medtronic HMS plus; Other Names: Heparin Leo; Hepalean

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Chest tube drainage	24 to 48 hrs

Secondary Outcome Measures

Outcome Measure	Time Frame
Amount of heparin used	1 to 7 hrs
Amount of Protamine used	1 to 7 hrs
Measured slope with heparin/ACT titration	1 to 7 hrs

Collaborators and Investigators

• Sponsor: Southlake Regional Health Centre
• Investigators: Principal Investigator: Charles M Peniston, MD,FRCP, Department of Cardiac surgery-S.R.H.C

Publications and helpful links

General Publications

• Dyck L, Friesen RM. Do different heparin brands influence activated clotting times? J Extra Corpor Technol. 1998 Jun;30(2):73-6.

Study record dates

Study Major Dates

• Study Start: September 1, 2006
• Primary Completion (Actual): December 1, 2007
• Study Completion (Actual): December 1, 2007

Study Registration Dates

• First Submitted: February 19, 2009
• First Submitted That Met QC Criteria: February 19, 2009
• First Posted (Estimate): February 20, 2009

Study Record Updates

• Last Update Posted (Estimate): February 20, 2009
• Last Update Submitted That Met QC Criteria: February 19, 2009
• Last Verified: February 1, 2009

More Information

Terms related to this study

• Keywords: Heparin Leo; Hepalean; CPB Cardiopuilmonary Bypass; CABG Coronary Artery Bypass Grafting; Anticoagulation efficacy
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Anticoagulants; Heparin; Calcium heparin
• Other Study ID Numbers: southlake