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

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01976988

Enrollment

410

Registered

2013-11-06

Start date

2013-09-30

Completion date

2015-05-31

Last updated

2016-10-14

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Venous Thromboembolism

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.

Interventions

DRUGHeparin

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

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

PREVENTION

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
Number of Participants With Postoperative VTE Within 48 Hours After Surgery	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

Measure	Time frame	Description
Number of Participants With Bleeding Complications	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
Number of Participants With Postoperative Thrombocytopenia	30 day postop period	Thrombocytopenia defined as \>50% or greater drop in platelet count
Number of Participants With Surgical Complications	30 day postop period	Major or minor medical and surgical complications
Hospital Stay	30 day postop period	Length of postoperative hospital stay
Number of Participants With VTE Within 30-day After Surgery	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.

Countries

United States

Participant flow

Participants by arm

Arm	Count
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 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	192
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 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	184
Total	376

Baseline characteristics

Characteristic	Post-op Heparin	Pre-op Heparin	Total
Age, Continuous	53.6 Years STANDARD_DEVIATION 18.2	51.7 Years STANDARD_DEVIATION 16.9	52.7 Years STANDARD_DEVIATION 17.6
Any Comorbidity Any Comorbidity	66 participants	54 participants	120 participants
Any Comorbidity No Comorbidity	126 participants	130 participants	256 participants
ASA Class 1	7 participants	9 participants	16 participants
ASA Class 2	114 participants	117 participants	231 participants
ASA Class 3	70 participants	57 participants	127 participants
ASA Class 4	1 participants	1 participants	2 participants
Body Mass Index	25.8 kg/m^2 STANDARD_DEVIATION 6.3	24.9 kg/m^2 STANDARD_DEVIATION 6.1	25 kg/m^2 STANDARD_DEVIATION 6.7
Conversion to Open Conversion to Open	11 participants	11 participants	22 participants
Conversion to Open No Conversion to Open	181 participants	173 participants	354 participants
Indication for Surgery Cancer	68 participants	66 participants	134 participants
Indication for Surgery Inflammatory Bowel Disease	72 participants	66 participants	138 participants
Indication for Surgery Other	52 participants	52 participants	104 participants
Operative Time	189 minutes	200 minutes	200 minutes
Preoperative Antiplatelet Therapy No Antiplatelet	165 participants	162 participants	327 participants
Preoperative Antiplatelet Therapy Received Antiplatelet	27 participants	22 participants	49 participants
Preoperative Hemoglobin g/dL	12.7 grams/dL STANDARD_DEVIATION 2	12.6 grams/dL STANDARD_DEVIATION 1.9	12.7 grams/dL STANDARD_DEVIATION 2
Preoperative Platelet Count	258 1000/uL	267 1000/uL	266 1000/uL
Prior Hospitalization No Prior Hospitalization	167 participants	147 participants	314 participants
Prior Hospitalization Prior Hosptialization	25 participants	37 participants	62 participants
Remote History of Venous Thromboembolism History VTE	1 participants	1 participants	2 participants
Remote History of Venous Thromboembolism No History VTE	191 participants	183 participants	374 participants
Sex: Female, Male Female	101 Participants	93 Participants	194 Participants
Sex: Female, Male Male	91 Participants	91 Participants	182 Participants
Smokers Non-Smoker	178 participants	172 participants	350 participants
Smokers Smoker	14 participants	12 participants	26 participants
Surgical Approach Hand-assisted laparoscopy	14 participants	29 participants	43 participants
Surgical Approach Laparoscopic/Robotic	105 participants	102 participants	207 participants
Surgical Approach Open	73 participants	53 participants	126 participants
Type of Resection Left Colon	52 participants	49 participants	101 participants
Type of Resection Proctectomy/Proctocolectomy	18 participants	23 participants	41 participants
Type of Resection Right Colon	51 participants	53 participants	104 participants
Type of Resection Small Bowel	29 participants	22 participants	51 participants
Type of Resection Total Abdominal Colectomy	42 participants	37 participants	79 participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	60 / 192	55 / 184
serious Total, serious adverse events	33 / 192	34 / 184

Outcome results

Primary

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

Time frame: 48 hour postop period

Arm	Measure	Value (NUMBER)
Post-op Heparin	Number of Participants With Postoperative VTE Within 48 Hours After Surgery	5 participants
Pre-op Heparin	Number of Participants With Postoperative VTE Within 48 Hours After Surgery	3 participants

p-value: 0.72Fisher Exact

Secondary