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

• ClinicalTrials.gov Identifier: NCT01976988
• Recruitment Status: Completed
• First Posted: November 6, 2013
• Results First Posted: October 14, 2016
• Last Update Posted: October 14, 2016
• Sponsor: Cedars-Sinai Medical Center
• Information provided by (Responsible Party): Phillip Fleshner MD, Cedars-Sinai Medical Center

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Venous Thromboembolism	Drug: Heparin	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 410 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: PROSPECTIVE STUDY ON PREOPERATIVE VERSUS POSTOPERATIVE VENOUS THROMBOPROPHYLAXIS IN PATIENTS UNDERGOING MAJOR COLORECTAL SURGERY
• Study Start Date: September 2013
• Actual Primary Completion Date: May 2015
• Actual Study Completion Date: May 2015

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Number of Participants With Postoperative VTE Within 48 Hours After Surgery [ Time Frame: 48 hour postop period ]
   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

Secondary Outcome Measures :

1. Number of Participants With Bleeding Complications [ Time Frame: 30 day postop period ]
   1. 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.
   2. 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
2. Number of Participants With Postoperative Thrombocytopenia [ Time Frame: 30 day postop period ]
   Thrombocytopenia defined as >50% or greater drop in platelet count
3. Number of Participants With Surgical Complications [ Time Frame: 30 day postop period ]
   Major or minor medical and surgical complications
4. Hospital Stay [ Time Frame: 30 day postop period ]
   Length of postoperative hospital stay
5. Number of Participants With VTE Within 30-day After Surgery [ Time Frame: 30 day postop period ]
   any VTE occuring within 30-days after surgery - clinical or asymptomatic - detected by venous duplex ultrasound, vq scan or ct pulmonary angiogram.

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, California

Cedars Sinai Medical Center

Los Angeles, California, United States, 90048

Sponsors and Collaborators

Cedars-Sinai Medical Center

Investigators

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

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Phillip Fleshner MD, Director of Colorectal Surgery Residency, Cedars-Sinai Medical Center
• ClinicalTrials.gov Identifier: NCT01976988
• Other Study ID Numbers: DVT
• First Posted: November 6, 2013
• Results First Posted: October 14, 2016
• Last Update Posted: October 14, 2016
• Last Verified: August 2016

Additional relevant MeSH terms:

Thromboembolism; Venous Thromboembolism; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Heparin; Anticoagulants; Fibrinolytic Agents; Fibrin Modulating Agents; Molecular Mechanisms of Pharmacological Action