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

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

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.

Study Overview

• Status: Completed
• Conditions: Venous Thromboembolism
• Intervention / Treatment: Drug: Heparin

• Study Type: Interventional
• Enrollment (Actual): 410
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90048
      • Cedars Sinai Medical Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Able to freely give written informed consent to participate in the study and have signed the Informed Consent Form;
2. Males or females, age 18 and older at the time of study screening;
3. American Society of Anesthesiologists (ASA) Class I-III (Appendix III);
4. Due to undergo major colorectal surgery via laparotomy or laparoscopy

Exclusion Criteria:

1. Mentally incompetent or unable or unwilling to provide informed consent or comply with study procedures;
2. American Society of Anesthesiologists (ASA) Class IV or V;
3. Children <18
4. Pregnant patients
5. Current/Active DVT
6. Patients on therapeutic anticoagulation for DVT or PE at time of surgery
7. Patients on anticoagulation for other medical problem (Heart Valve/atrial fibrillation) at the time of surgery
8. Patients with IVC filter
9. History of allergy to heparin products
10. History of heparin induced thrombocytopenia (HIT)
11. Patients with recent or active hemorrhage (GI/intracranial, etc) felt by the attending surgeon to be a contraindication to heparin thromboprophylaxis
12. Patients with Epidural analgesia

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Post-op Heparin; 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; 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
Experimental: Pre-op Heparin; 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; 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Cedars-Sinai Medical Center
• Investigators: Principal Investigator: Phillip Fleshner, M.D, Cedars-Sinai Medical Center

Publications and helpful links

General Publications

• Zaghiyan KN, Sax HC, Miraflor E, Cossman D, Wagner W, Mirocha J, Gewertz B, Fleshner P; Cedars-Sinai DVT Study Group. Timing of Chemical Thromboprophylaxis and Deep Vein Thrombosis in Major Colorectal Surgery: A Randomized Clinical Trial. Ann Surg. 2016 Oct;264(4):632-9. doi: 10.1097/SLA.0000000000001856.

Study record dates

Study Major Dates

• Study Start: September 1, 2013
• Primary Completion (Actual): May 1, 2015
• Study Completion (Actual): May 1, 2015

Study Registration Dates

• First Submitted: September 24, 2013
• First Submitted That Met QC Criteria: November 5, 2013
• First Posted (Estimate): November 6, 2013

Study Record Updates

• Last Update Posted (Estimate): October 14, 2016
• Last Update Submitted That Met QC Criteria: August 21, 2016
• Last Verified: August 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Embolism and Thrombosis; Thromboembolism; Venous Thromboembolism; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Anticoagulants; Heparin
• Other Study ID Numbers: DVT