Clinical trial NCT02812355: Randomized Anticoagulation Trial in Opcab (RATIO)
Official title: High Dose Versus Low Dose Heparinization in Patients Undergoing Offpump Coronary Artery Bypass
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Ischemic Heart Disease
Keywords: off-pump
coronary artery bypass
heparinization
Lead sponsor: Azienda Ospedaliera di Lecco
Sponsor class: OTHER
First posted: 2016-06-24
Enrollment: 900
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Composite vascular
timeFrame: 30 days post-operatively
measure: Composite major bleeding
timeFrame: 48 hours post-operatively
Secondary outcomes:
measure: Post-operative bleeding
timeFrame: 48 hours post-operatively
measure: Transfusion of packed red cells (<3 Units) or of platelets
timeFrame: 30 days post-operatively
measure: Peak value of cardiac biomarker
timeFrame: 30 days post-operatively
measure: Transient ischemic cerebral attack
timeFrame: 30 days post-operatively
measure: Mesenteric ischemia (angiography or CT scan)
timeFrame: 30 days post-operatively
measure: Pulmonary embolus (angiography or CT scan)
timeFrame: 30 days post-operatively
Other outcomes:
Locations:
city: Changchun
country: China
facility: Jilin Heart Hospital
state: Jilin
city: Lecco
country: Italy
facility: ASST Lecco
city: Sassari
country: Italy
facility: Azienda Ospedaliera Universitaria di Sassari
Study officials:
affiliation: ASST Lecco
name: Michele NR Triggiani, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: