PREvention of VENous ThromboEmbolism Following Radical Prostatectomy (PREVENTER)

A Randomized Controlled Trial for PREvention of VENous ThromboEmbolism Following Radical Prostatectomy (PREVENTER Trial)

The PREVENTER Trial aims to compare the use of perioperative pharmacologic prophylaxis (subcutaneous heparin) with intermittent pneumatic compression devices (IPCs) to the use of IPCs alone for the prevention of venous thromboembolism (VTE) after radical prostatectomy (RP).

Study Overview

• Status: Terminated
• Conditions: Prostate Cancer; Venous Thromboembolism; Pulmonary Embolism; Deep Venous Thrombosis; Lymphocele After Surgical Procedure
• Intervention / Treatment: Drug: Subcutaneous Heparin

Detailed Description

The PREVENTER Trial aims to compare the use of perioperative pharmacologic prophylaxis (subcutaneous heparin) with intermittent pneumatic compression devices (IPCs) to the use of IPCs alone for the prevention of venous thromboembolism (VTE) after radical prostatectomy (RP). Currently, there is no standard practice for VTE prophylaxis after RP with the American Urological Association recommending "pharmacological or pneumatic mechanical prophylaxis" for high risk patients. Prior studies showed 30% of patients in the United States received no perioperative prophylaxis and less than 20% received pharmacologic agents, compared to 98% of patients receiving pharmacologic prophylaxis in the United Kingdom. Some urologists prescribe patients low molecular weight heparin (LMWH) after discharge for up to 30 days after surgery. Additionally, there are no established risks of pharmacologic prophylaxis for RP patients, but some urologists express concern about the potential impact of prophylaxis on the rate of postoperative lymphoceles or hematomas. At Johns Hopkins, patients do not routinely receive pharmacologic VTE prophylaxis in the perioperative setting for RP. Given the lack of standard practice and implications for patient safety, the investigators propose a prospective, stratified randomized controlled trial to evaluate the impact of perioperative pharmacologic prophylaxis on VTE following RP hypothesizing that it will prevent VTE events without significantly impacting the rate of postoperative bleeding or lymphoceles. The potential impact of surveillance bias with differential imaging between arms, effect of lymphadenectomy (yes/no and number of noted removed) or surgical approach (robotic and open), and differences by patients risk (comorbidity and VTE risk based on components of the Caprini score) or demographics will be assessed.

• Study Type: Interventional
• Enrollment (Actual): 501
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 98 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Men 18-100 years of age with histologically confirmed prostate cancer of any stage undergoing RP
• Patients who would have otherwise been eligible to receive routine post-RP care

Exclusion Criteria:

• Active treatment for VTE
• Patients judged by patients' urologist, primary care doctor, or in the preoperative evaluation center (PEC) to be unsafe to forgo pharmacologic prophylaxis or systemic anticoagulation postoperatively (whether or not patients are on systematic anticoagulation for indications other than VTE)
• Known adverse reactions to heparin (heparin-induced thrombocytopenia or any allergy)
• Epidural analgesia
• Spinal anesthesia
• Participation in a different trial that increases a patient's risk of VTE

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Subcutaneous Heparin; Patients randomized to the pharmacologic VTE prophylaxis arm will receive a dose of subcutaneous heparin 5,000 units prior to incision, and subcutaneous heparin 5,000 units every 8 hours after surgery until discharge.	Drug: Subcutaneous Heparin; 5,000 units of subcutaneous heparin before surgery and then every 8 hours after surgery until discharge from the hospital.
No Intervention: Control; Patients randomized to the control arm will receive routine care with intermittent pneumatic compression devices.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Symptomatic Venous Thromboembolism	Venous thromboembolism (VTE) is a disease that includes both deep vein thrombosis (DVT) and pulmonary embolism (PE). The primary outcome is diagnosis of DVT or PE within 30 days after surgery due to imaging (any method, most commonly lower extremity ultrasound or computed tomography scan with pulmonary embolus protocol) prompted by symptoms of a DVT (lower extremity swelling, pain, fever of unknown origin) or PE (chest pain, shortness of breath, hypoxemia, tachycardia or fever of unknown origin, productive cough with bloody sputum).	30 days
Number of Participants With Symptomatic Postoperative Fluid Collection	This outcome is defined as a surgical or pelvic fluid collection diagnosed as a hematoma (blood collection, with or without infection) or lymphocele (collection of lymph fluid in the pelvis) due to symptoms (fever, abdominal pain, nausea or vomiting, anemia, high surgical drain output) within 30 days after surgery.	30 days
Number of Participants With Major Postoperative Bleeding	This additional primary outcome includes the development and diagnosis of any major clinically recognized bleeding event within 30 days after surgery requiring >1 unit of packed red blood cell transfusion, intervention to stop bleeding, or return to the operating room.	30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Occurrence of Any Venous Thromboembolism	DVT or PE diagnosed for any reason within 30 days after surgery. This includes any diagnosed DVT or PE as described in the primary outcome plus any additional DVTs or PEs diagnosed at 30 day screening lower extremity ultrasound for patients opting to undergo screening bilateral lower extremity Duplex ultrasound at 30 days who do not have symptoms.	30 days
Estimated Blood Loss During Surgery	The total recorded intraoperative estimated blood loss in milliliters reported at the end of the surgery.	During surgery (usually between 2-3 hours of operative time)
Surgical Drain Output After Surgery	The total output in milliliters from any surgical drain left in place (not all patients will necessarily have a surgical drain) after surgery and until discharge from the hospital (usually 1 to 2 days). Drain output, if one is left in place after discharge, will not count toward this secondary outcome.	Over length of stay in hospital (usually 1 to 2 days)
Surveillance Bias by Differential Use of Imaging as Assessed by Number of Participants Receiving Postoperative Diagnostic Imaging for Venous Thromboembolism Relative to Symptoms	Patients in each arm receiving postoperative diagnostic imaging for venous thromboembolism relative to symptoms (e.g. lower extremity Duplex ultrasound, spiral CT angiography, V/Q scan).	30 days

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Investigators: Principal Investigator: Mohamad E Allaf, MD, Johns Hopkins University

Publications and helpful links

General Publications

• Huang MM, Su ZT, Becker REN, Pavlovich CP, Partin AW, Allaf ME, Patel HD. Complications after open and robot-assisted radical prostatectomy and association with postoperative opioid use: an analysis of data from the PREVENTER trial. BJU Int. 2021 Feb;127(2):190-197. doi: 10.1111/bju.15172. Epub 2020 Aug 17.
• Patel HD, Faisal FA, Trock BJ, Joice GA, Schwen ZR, Pierorazio PM, Johnson MH, Bivalacqua TJ, Han M, Gorin MA, Carter HB, Partin AW, Pavlovich CP, Allaf ME. Effect of Pharmacologic Prophylaxis on Venous Thromboembolism After Radical Prostatectomy: The PREVENTER Randomized Clinical Trial. Eur Urol. 2020 Sep;78(3):360-368. doi: 10.1016/j.eururo.2020.05.001. Epub 2020 May 19.
• Patel HD, Faisal FA, Patel ND, Pavlovich CP, Allaf ME, Han M, Herati AS. Effect of a prospective opioid reduction intervention on opioid prescribing and use after radical prostatectomy: results of the Opioid Reduction Intervention for Open, Laparoscopic, and Endoscopic Surgery (ORIOLES) Initiative. BJU Int. 2020 Mar;125(3):426-432. doi: 10.1111/bju.14932. Epub 2019 Nov 15.
• Patel HD, Srivastava A, Patel ND, Faisal FA, Ludwig W, Joice GA, Schwen ZR, Allaf ME, Han M, Herati AS. A Prospective Cohort Study of Postdischarge Opioid Practices After Radical Prostatectomy: The ORIOLES Initiative. Eur Urol. 2019 Feb;75(2):215-218. doi: 10.1016/j.eururo.2018.10.013. Epub 2018 Oct 21.

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2017
• Primary Completion (Actual): November 1, 2019
• Study Completion (Actual): November 1, 2019

Study Registration Dates

• First Submitted: December 27, 2016
• First Submitted That Met QC Criteria: December 27, 2016
• First Posted (Estimate): December 30, 2016

Study Record Updates

• Last Update Posted (Actual): August 5, 2020
• Last Update Submitted That Met QC Criteria: July 27, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Neoplasms; Lymphatic Diseases; Lung Diseases; Cysts; Embolism and Thrombosis; Embolism; Thrombosis; Venous Thrombosis; Thromboembolism; Venous Thromboembolism; Pulmonary Embolism; Lymphocele; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Anticoagulants; Heparin
• Other Study ID Numbers: IRB00123618

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No