Trial Outcomes & Findings for Prospective Study on Preoperative Versus Postoperative Venous Thromboprophylaxis in Patients Undergoing Major Colorectal Surgery (NCT NCT01976988)

NCT ID: NCT01976988

Last Updated: 2016-10-14

Results Overview

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

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 410 participants
• Primary outcome timeframe: 48 hour postop period
• Results posted on: 2016-10-14

Participant Flow

Participant milestones

Measure	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 started 23 hours after the end of surgery and continued every 8 hours for the remainder of the patients hospital course	Pre-op Heparin Treatment arm: subcutaneous Heparin 5000 Units given in the preoperative area prior to surgery, then 8 hours after surgery and continued every 8 hours for the remainder of the patients hospital course Heparin: Subcutaneous Heparin 5000 Units given in the preoperative area prior to surgery, then 8 hours after surgery and continued every 8 hours for the remainder of the patients hospital course
Overall Study STARTED	208	202
Overall Study COMPLETED	192	184
Overall Study NOT COMPLETED	16	18

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Post-op Heparin n=192 Participants 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	Pre-op Heparin n=184 Participants 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	Total n=376 Participants Total of all reporting groups
Age, Continuous	53.6 Years STANDARD_DEVIATION 18.2 • n=5 Participants	51.7 Years STANDARD_DEVIATION 16.9 • n=7 Participants	52.7 Years STANDARD_DEVIATION 17.6 • n=5 Participants
Sex: Female, Male Female	101 Participants n=5 Participants	93 Participants n=7 Participants	194 Participants n=5 Participants
Sex: Female, Male Male	91 Participants n=5 Participants	91 Participants n=7 Participants	182 Participants n=5 Participants
Body Mass Index	25.8 kg/m^2 STANDARD_DEVIATION 6.3 • n=5 Participants	24.9 kg/m^2 STANDARD_DEVIATION 6.1 • n=7 Participants	25 kg/m^2 STANDARD_DEVIATION 6.7 • n=5 Participants
Any Comorbidity Any Comorbidity	66 participants n=5 Participants	54 participants n=7 Participants	120 participants n=5 Participants
Any Comorbidity No Comorbidity	126 participants n=5 Participants	130 participants n=7 Participants	256 participants n=5 Participants
ASA Class 1	7 participants n=5 Participants	9 participants n=7 Participants	16 participants n=5 Participants
ASA Class 2	114 participants n=5 Participants	117 participants n=7 Participants	231 participants n=5 Participants
ASA Class 3	70 participants n=5 Participants	57 participants n=7 Participants	127 participants n=5 Participants
ASA Class 4	1 participants n=5 Participants	1 participants n=7 Participants	2 participants n=5 Participants
Smokers Smoker	14 participants n=5 Participants	12 participants n=7 Participants	26 participants n=5 Participants
Smokers Non-Smoker	178 participants n=5 Participants	172 participants n=7 Participants	350 participants n=5 Participants
Preoperative Antiplatelet Therapy Received Antiplatelet	27 participants n=5 Participants	22 participants n=7 Participants	49 participants n=5 Participants
Preoperative Antiplatelet Therapy No Antiplatelet	165 participants n=5 Participants	162 participants n=7 Participants	327 participants n=5 Participants
Remote History of Venous Thromboembolism History VTE	1 participants n=5 Participants	1 participants n=7 Participants	2 participants n=5 Participants
Remote History of Venous Thromboembolism No History VTE	191 participants n=5 Participants	183 participants n=7 Participants	374 participants n=5 Participants
Prior Hospitalization Prior Hosptialization	25 participants n=5 Participants	37 participants n=7 Participants	62 participants n=5 Participants
Prior Hospitalization No Prior Hospitalization	167 participants n=5 Participants	147 participants n=7 Participants	314 participants n=5 Participants
Indication for Surgery Cancer	68 participants n=5 Participants	66 participants n=7 Participants	134 participants n=5 Participants
Indication for Surgery Inflammatory Bowel Disease	72 participants n=5 Participants	66 participants n=7 Participants	138 participants n=5 Participants
Indication for Surgery Other	52 participants n=5 Participants	52 participants n=7 Participants	104 participants n=5 Participants
Type of Resection Small Bowel	29 participants n=5 Participants	22 participants n=7 Participants	51 participants n=5 Participants
Type of Resection Right Colon	51 participants n=5 Participants	53 participants n=7 Participants	104 participants n=5 Participants
Type of Resection Left Colon	52 participants n=5 Participants	49 participants n=7 Participants	101 participants n=5 Participants
Type of Resection Total Abdominal Colectomy	42 participants n=5 Participants	37 participants n=7 Participants	79 participants n=5 Participants
Type of Resection Proctectomy/Proctocolectomy	18 participants n=5 Participants	23 participants n=7 Participants	41 participants n=5 Participants
Surgical Approach Open	73 participants n=5 Participants	53 participants n=7 Participants	126 participants n=5 Participants
Surgical Approach Hand-assisted laparoscopy	14 participants n=5 Participants	29 participants n=7 Participants	43 participants n=5 Participants
Surgical Approach Laparoscopic/Robotic	105 participants n=5 Participants	102 participants n=7 Participants	207 participants n=5 Participants
Conversion to Open Conversion to Open	11 participants n=5 Participants	11 participants n=7 Participants	22 participants n=5 Participants
Conversion to Open No Conversion to Open	181 participants n=5 Participants	173 participants n=7 Participants	354 participants n=5 Participants
Preoperative Hemoglobin g/dL	12.7 grams/dL STANDARD_DEVIATION 2 • n=5 Participants	12.6 grams/dL STANDARD_DEVIATION 1.9 • n=7 Participants	12.7 grams/dL STANDARD_DEVIATION 2 • n=5 Participants
Preoperative Platelet Count	258 1000/uL n=5 Participants	267 1000/uL n=7 Participants	266 1000/uL n=5 Participants
Operative Time	189 minutes n=5 Participants	200 minutes n=7 Participants	200 minutes n=5 Participants

PRIMARY outcome

Timeframe: 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

Outcome measures

Measure	Post-op Heparin n=192 Participants 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 started 23 hours after the end of surgery and continued every 8 hours for the remainder of the patients hospital course	Pre-op Heparin n=184 Participants Treatment arm: subcutaneous Heparin 5000 Units given in the preoperative area prior to surgery, then 8 hours after surgery and continued every 8 hours for the remainder of the patients hospital course Heparin: Subcutaneous Heparin 5000 Units given in the preoperative area prior to surgery, then 8 hours after surgery and continued every 8 hours for the remainder of the patients hospital course
Number of Participants With Postoperative VTE Within 48 Hours After Surgery	5 participants	3 participants

SECONDARY outcome

Timeframe: 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

Outcome measures

Measure	Post-op Heparin n=192 Participants 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 started 23 hours after the end of surgery and continued every 8 hours for the remainder of the patients hospital course	Pre-op Heparin n=184 Participants Treatment arm: subcutaneous Heparin 5000 Units given in the preoperative area prior to surgery, then 8 hours after surgery and continued every 8 hours for the remainder of the patients hospital course Heparin: Subcutaneous Heparin 5000 Units given in the preoperative area prior to surgery, then 8 hours after surgery and continued every 8 hours for the remainder of the patients hospital course
Number of Participants With Bleeding Complications	58 participants	47 participants

SECONDARY outcome

Timeframe: 30 day postop period

Thrombocytopenia defined as >50% or greater drop in platelet count

Outcome measures

Measure	Post-op Heparin n=192 Participants 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 started 23 hours after the end of surgery and continued every 8 hours for the remainder of the patients hospital course	Pre-op Heparin n=184 Participants Treatment arm: subcutaneous Heparin 5000 Units given in the preoperative area prior to surgery, then 8 hours after surgery and continued every 8 hours for the remainder of the patients hospital course Heparin: Subcutaneous Heparin 5000 Units given in the preoperative area prior to surgery, then 8 hours after surgery and continued every 8 hours for the remainder of the patients hospital course
Number of Participants With Postoperative Thrombocytopenia	0 participants	5 participants

SECONDARY outcome

Timeframe: 30 day postop period

Major or minor medical and surgical complications

Outcome measures

Measure	Post-op Heparin n=192 Participants 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 started 23 hours after the end of surgery and continued every 8 hours for the remainder of the patients hospital course	Pre-op Heparin n=184 Participants Treatment arm: subcutaneous Heparin 5000 Units given in the preoperative area prior to surgery, then 8 hours after surgery and continued every 8 hours for the remainder of the patients hospital course Heparin: Subcutaneous Heparin 5000 Units given in the preoperative area prior to surgery, then 8 hours after surgery and continued every 8 hours for the remainder of the patients hospital course
Number of Participants With Surgical Complications	76 participants	72 participants

SECONDARY outcome

Timeframe: 30 day postop period

Length of postoperative hospital stay

Outcome measures

Measure	Post-op Heparin n=192 Participants 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 started 23 hours after the end of surgery and continued every 8 hours for the remainder of the patients hospital course	Pre-op Heparin n=184 Participants Treatment arm: subcutaneous Heparin 5000 Units given in the preoperative area prior to surgery, then 8 hours after surgery and continued every 8 hours for the remainder of the patients hospital course Heparin: Subcutaneous Heparin 5000 Units given in the preoperative area prior to surgery, then 8 hours after surgery and continued every 8 hours for the remainder of the patients hospital course
Hospital Stay	5 days Interval 4.0 to 7.0	4.5 days Interval 3.0 to 7.0

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Post-op Heparin n=192 Participants 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 started 23 hours after the end of surgery and continued every 8 hours for the remainder of the patients hospital course	Pre-op Heparin n=184 Participants Treatment arm: subcutaneous Heparin 5000 Units given in the preoperative area prior to surgery, then 8 hours after surgery and continued every 8 hours for the remainder of the patients hospital course Heparin: Subcutaneous Heparin 5000 Units given in the preoperative area prior to surgery, then 8 hours after surgery and continued every 8 hours for the remainder of the patients hospital course
Number of Participants With VTE Within 30-day After Surgery	7 participants	3 participants

Adverse Events

Post-op Heparin

Serious events: 33 serious events

Other events: 60 other events

Deaths: 0 deaths

Pre-op Heparin

Serious events: 34 serious events

Other events: 55 other events

Deaths: 0 deaths

Serious adverse events

Measure	Post-op Heparin n=192 participants at risk 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 started 23 hours after the end of surgery and continued every 8 hours for the remainder of the patients hospital course	Pre-op Heparin n=184 participants at risk Treatment arm: subcutaneous Heparin 5000 Units given in the preoperative area prior to surgery, then 8 hours after surgery and continued every 8 hours for the remainder of the patients hospital course Heparin: Subcutaneous Heparin 5000 Units given in the preoperative area prior to surgery, then 8 hours after surgery and continued every 8 hours for the remainder of the patients hospital course
Blood and lymphatic system disorders Bleeding requiring reoperation	1.6% 3/192 • Number of events 3 • Adverse events related to heparin during the 30-day postoperative period was assessed	1.1% 2/184 • Number of events 2 • Adverse events related to heparin during the 30-day postoperative period was assessed
Infections and infestations Gastrointerstinal complications	12.0% 23/192 • Number of events 23 • Adverse events related to heparin during the 30-day postoperative period was assessed	12.5% 23/184 • Number of events 23 • Adverse events related to heparin during the 30-day postoperative period was assessed
Infections and infestations Infectious complications	2.1% 4/192 • Number of events 4 • Adverse events related to heparin during the 30-day postoperative period was assessed	2.2% 4/184 • Number of events 4 • Adverse events related to heparin during the 30-day postoperative period was assessed
Renal and urinary disorders Urinary retention	1.0% 2/192 • Number of events 2 • Adverse events related to heparin during the 30-day postoperative period was assessed	1.1% 2/184 • Number of events 2 • Adverse events related to heparin during the 30-day postoperative period was assessed
Cardiac disorders Cardiac	0.00% 0/192 • Adverse events related to heparin during the 30-day postoperative period was assessed	1.1% 2/184 • Number of events 2 • Adverse events related to heparin during the 30-day postoperative period was assessed
Respiratory, thoracic and mediastinal disorders Pulmonary complication	0.52% 1/192 • Number of events 1 • Adverse events related to heparin during the 30-day postoperative period was assessed	0.54% 1/184 • Number of events 1 • Adverse events related to heparin during the 30-day postoperative period was assessed

Other adverse events

Measure	Post-op Heparin n=192 participants at risk 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 started 23 hours after the end of surgery and continued every 8 hours for the remainder of the patients hospital course	Pre-op Heparin n=184 participants at risk Treatment arm: subcutaneous Heparin 5000 Units given in the preoperative area prior to surgery, then 8 hours after surgery and continued every 8 hours for the remainder of the patients hospital course Heparin: Subcutaneous Heparin 5000 Units given in the preoperative area prior to surgery, then 8 hours after surgery and continued every 8 hours for the remainder of the patients hospital course
Blood and lymphatic system disorders Bleeding not requiring reoperation	11.5% 22/192 • Number of events 22 • Adverse events related to heparin during the 30-day postoperative period was assessed	12.5% 23/184 • Number of events 23 • Adverse events related to heparin during the 30-day postoperative period was assessed
Infections and infestations Infections treated conservatively	2.6% 5/192 • Adverse events related to heparin during the 30-day postoperative period was assessed	3.8% 7/184 • Adverse events related to heparin during the 30-day postoperative period was assessed
Cardiac disorders Cardiac events	0.00% 0/192 • Adverse events related to heparin during the 30-day postoperative period was assessed	1.1% 2/184 • Number of events 2 • Adverse events related to heparin during the 30-day postoperative period was assessed
Renal and urinary disorders Genitourinary complications	5.2% 10/192 • Number of events 10 • Adverse events related to heparin during the 30-day postoperative period was assessed	3.8% 7/184 • Number of events 7 • Adverse events related to heparin during the 30-day postoperative period was assessed
Blood and lymphatic system disorders superficial venous thrombosis	0.52% 1/192 • Number of events 1 • Adverse events related to heparin during the 30-day postoperative period was assessed	0.00% 0/184 • Adverse events related to heparin during the 30-day postoperative period was assessed
Blood and lymphatic system disorders gastrointestinal complications	14.1% 27/192 • Number of events 27 • Adverse events related to heparin during the 30-day postoperative period was assessed	12.5% 23/184 • Number of events 23 • Adverse events related to heparin during the 30-day postoperative period was assessed

Additional Information

Phillip Fleshner MD

Cedars Sinai Medical Center

Phone: 310-289-9224

Email: pfleshner@aol.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place