Prospective Study on Preoperative Versus Postoperative Venous Thromboprophylaxis in Patients Undergoing Major Colorectal Surgery

Study Overview
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Brief Summary
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Patients undergoing major colorectal surgery are at increased risk for VTE (deep venous thrombosis) compared with patients undergoing other general surgical procedures (Bergqvist et al. Dis. Col. Rectum. 2006; 49: 1620-1628.) The reported incidence of symptomatic VTE after colorectal surgery is approximately 4% (Monn, F. et al. JACS. 216; 2013: 395-401). However, the reported incidence of VTE after colorectal surgery in prospectively followed patients managed with perioperative venous thromboprophylaxis undergoing screening venography prior to hospital discharge ranges from 9 to 20% (Bergovist et al. NEJM 346; 2002: 975-980; McLeod et al. Ann. Surg. 233; 2000: 438-444; ENOXACAN Study group. Brit. J. Surg. 84; 1997: 1099-1103. The Surgical Care Improvement Project (SCIP) and the American College of Chest Physician (ACCP) guidelines recommend that venous thromboprophylaxis be initiated within 24 hours of surgery. However, it is believed that deep venous thrombosis occurs during surgery, rather than in the postoperative period, justifying preoperative initiation of venous thromboprophylaxis. This practice is accompanied with a theoretically higher risk of bleeding complications. Currently there is no consensus on the precise timing of VTE prophylaxis after major colorectal surgery, as demonstrated by the vague guidelines established by the ACCP and SCIP. Current studies on VTE prophylaxis report preoperative initiation of VTE prophylaxis. However, majority of surgeons at our institution begin heparin postoperatively given concern for bleeding complications with preoperative dosing of heparin. The purpose of this study is to prospectively evaluate the incidence of VTE and major bleeding complications in patients undergoing major colorectal surgery who are treated with preoperative or postoperative venous thromboprophylaxis and to help establish more stringent guidelines on the optimal timing of VTE prophylaxis.

Official Title
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PROSPECTIVE STUDY ON PREOPERATIVE VERSUS POSTOPERATIVE VENOUS THROMBOPROPHYLAXIS IN PATIENTS UNDERGOING MAJOR COLORECTAL SURGERY

Conditions
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Venous Thromboembolism

Intervention / Treatment
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* Drug: Heparin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Able to freely give written informed consent to participate in the study and have signed the Informed Consent Form; Males or females, age 18 and older at the time of study screening; American Society of Anesthesiologists (ASA) Class I-III (Appendix III); Due to undergo major colorectal surgery via laparotomy or laparoscopy Exclusion Criteria: Mentally incompetent or unable or unwilling to provide informed consent or comply with study procedures; American Society of Anesthesiologists (ASA) Class IV or V; Children <18 Pregnant patients Current/Active DVT Patients on therapeutic anticoagulation for DVT or PE at time of surgery Patients on anticoagulation for other medical problem (Heart Valve/atrial fibrillation) at the time of surgery Patients with IVC filter History of allergy to heparin products History of heparin induced thrombocytopenia (HIT) Patients with recent or active hemorrhage (GI/intracranial, etc) felt by the attending surgeon to be a contraindication to heparin thromboprophylaxis Patients with Epidural analgesia

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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Post-op Heparin<br>Postoperative venous thromboprophylaxis (Control Arm/current standard practice: subcutaneous Heparin 5000 units started 23 hours after the end of surgery and continued every 8 hours for the remainder of the patients hospital course | Drug: Heparin<br>* Subcutaneous Heparin 5000 Units given in the preoperative area one hour prior to surgery and continued every 8 hours for the remainder of the patients hospital course<br>|
| Experimental: Pre-op Heparin<br>Treatment arm: subcutaneous Heparin 5000 Units given in the preoperative area one hour prior to surgery and continued every 8 hours for the remainder of the patients hospital course | Drug: Heparin<br>* Subcutaneous Heparin 5000 Units given in the preoperative area one hour prior to surgery and continued every 8 hours for the remainder of the patients hospital course<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Postoperative VTE Within 48 Hours After Surgery | Number of participants with postoperative VTE (deep venous thrombosis (DVT) or pulmonary embolism (PE) as demonstrated by duplex sonography or high probability on ventilation-perfusion scan or CT chest angiography within 48 hour postop period | 48 hour postop period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Bleeding Complications | Major bleeding defined as any intracranial or intraocular hemorrhage or bleeding from any site associated with >2g/dL drop in hemoglobin or transfusion of >2 unit packed RBCs (including operative site bleeding, unexpected upper or lower gastrointestinal hemorrhage, or retroperitoneal hemorrhage) or any hemorrhage needing surgical intervention/reoperation or leading to death. Minor bleeding defined as wound hematoma, ecchymosis >10 cm, epistaxis of more than 2 minute duration, macroscopic hematuria, unexpected upper or lower GI hemorrhage associated with <2g/dL drop in hemoglobin or <2 unit packed RBC transfusion | 30 day postop period | 
| Number of Participants With Postoperative Thrombocytopenia | Thrombocytopenia defined as >50% or greater drop in platelet count | 30 day postop period | 
| Number of Participants With Surgical Complications | Major or minor medical and surgical complications | 30 day postop period | 
| Hospital Stay | Length of postoperative hospital stay | 30 day postop period | 
| Number of Participants With VTE Within 30-day After Surgery | any VTE occuring within 30-days after surgery - clinical or asymptomatic - detected by venous duplex ultrasound, vq scan or ct pulmonary angiogram. | 30 day postop period |