Randomized Anticoagulation Trial in Opcab (RATIO)

Study Overview
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Brief Summary
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The RATIO Study is a multicenter, nationwide, randomized, controlled, single blinded, unfunded trial of n. 900 patients undergoing multivessel OPCAB (≥2 grafts). This study is designed to test in patients undergoing off-pump coronary artery bypass surgery the hypothesis that full (high dose, 300 U/kg) and half (low dose,150 U/kg) heparinization are not different in terms of thrombotic complications and major perioperative bleeding events (null hypothesis).

Detailed Description
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Off-pump coronary artery bypass grafting (OPCAB) is an established alternative to on-pump coronary artery bypass grafting (CABG). OPCAB determines a pro-coagulant state potentially deleterious on grafts patency, that is not counterbalanced by the adverse effects of cardiopulmonary bypass on coagulation occurring in CABG, and that lasts as long as one month. Therefore in OPCAB systemic heparinization is necessary to prevent thrombotic complications during transitory occlusion of coronary arteries and grafts. An internationally accepted standard intra-operative anticoagulation protocol for OPCAB has not yet been defined, and heparinization in OPCAB is a highly variable practice. The intraoperative anticoagulation regimen adopted in patients undergoing OPCAB may influence major postoperative outcomes, such as bleeding, transfusion requirements, inflammatory response, myocardial ischemia and grafts patency, but it has never been the object of large-scale randomized controlled trial (RCT). The 2 most widespread intraoperative anticoagulation protocols in OPCAB are represented by full (300 U/kg) or half (150 U/kg) heparinization, with target ACT ranging from 200 sec to >480 sec. Patients enrolled in the study will be randomized to receive full or half heparinization in a 1:1 ratio using a randomization schedule blocked by site. Randomization will take place in the operatory room by the anesthesiologist, and will be blinded to the surgeon.

Official Title
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High Dose Versus Low Dose Heparinization in Patients Undergoing Offpump Coronary Artery Bypass

Conditions
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Ischemic Heart Disease

Intervention / Treatment
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* Drug: Heparin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Consecutive patients electively undergoing multivessel OPCAB Exclusion Criteria: Acute coronary syndrome, on-going double anti-platelets treatment (the second antiplatelet drug should be suspended 5 days before surgery), on-going intravenous heparin or sub-cutaneous low molecular weight heparin, known coagulopathy, documented liver disease, chronic renal failure (creatinine ≥ 2 mg/dl) or previous renal transplantation surgery, previous cardiac surgery.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: half heparinization<br>heparin I.V. 150 U/kg | Drug: Heparin<br> <br> |
| Active Comparator: full heparinization (300 U/kg)<br>heparin I.V. 300 U/kg | Drug: Heparin<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite vascular | Death from vascular causes, perioperative myocardial infarction, stroke. | 30 days post-operatively | 
| Composite major bleeding | Redo for excessive bleeding, cardiac tamponade, transfusion ≥3 Units of packed red cells or of platelets. | 48 hours post-operatively | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Post-operative bleeding | Total bleeding evaluated the morning after surgery (ml.) | 48 hours post-operatively | 
| Transfusion of packed red cells (<3 Units) or of platelets |  | 30 days post-operatively | 
| Peak value of cardiac biomarker |  | 30 days post-operatively | 
| Transient ischemic cerebral attack |  | 30 days post-operatively | 
| Mesenteric ischemia (angiography or CT scan) |  | 30 days post-operatively | 
| Pulmonary embolus (angiography or CT scan) |  | 30 days post-operatively | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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off-pump, coronary artery bypass, heparinization