Deep Venous Thrombosis, Lymphocele After Surgical Procedure, Prostate Cancer, Pulmonary Embolism, Venous Thromboembolism
Conditions
Brief summary
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).
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.
Interventions
5,000 units of subcutaneous heparin before surgery and then every 8 hours after surgery until discharge from the hospital.
Sponsors
Johns Hopkins University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Outcomes Assessor)
Intervention model description
Prospective, single-institution, multi-surgeon, stratified randomized controlled trial. Randomization will be stratified into four groups by procedure approach (open or robotic) and whether patients elect to undergo a screening 30-day lower extremity Duplex (ultrasound or no ultrasound). Patients will then be randomized, within each of the strata, to the two arms (subcutaneous heparin versus no subcutaneous heparin).
Eligibility
Sex/Gender
MALE
Age
18 Years to 100 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Symptomatic Venous Thromboembolism | 30 days | 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). |
| Number of Participants With Symptomatic Postoperative Fluid Collection | 30 days | 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. |
| Number of Participants With Major Postoperative Bleeding | 30 days | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Occurrence of Any Venous Thromboembolism | 30 days | 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. |
| Surveillance Bias by Differential Use of Imaging as Assessed by Number of Participants Receiving Postoperative Diagnostic Imaging for Venous Thromboembolism Relative to Symptoms | 30 days | 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). |
| Estimated Blood Loss During Surgery | During surgery (usually between 2-3 hours of operative time) | The total recorded intraoperative estimated blood loss in milliliters reported at the end of the surgery. |
| Surgical Drain Output After Surgery | Over length of stay in hospital (usually 1 to 2 days) | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
Subcutaneous Heparin: 5,000 units of subcutaneous heparin before surgery and then every 8 hours after surgery until discharge from the hospital. | 251 |
| Control Patients randomized to the control arm will receive routine care with intermittent pneumatic compression devices. | 250 |
| Total | 501 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 1 |
Baseline characteristics
| Characteristic | Control | Total | Subcutaneous Heparin |
|---|---|---|---|
| Age, Continuous | 61 years | 62 years | 63 years |
| Race/Ethnicity, Customized African American | 39 Participants | 73 Participants | 34 Participants |
| Race/Ethnicity, Customized Asian | 5 Participants | 14 Participants | 9 Participants |
| Race/Ethnicity, Customized Hispanic | 2 Participants | 10 Participants | 8 Participants |
| Race/Ethnicity, Customized White | 204 Participants | 404 Participants | 200 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 250 Participants | 501 Participants | 251 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 251 | 0 / 250 |
| other Total, other adverse events | 34 / 251 | 30 / 250 |
| serious Total, serious adverse events | 9 / 251 | 9 / 250 |
Outcome results
Primary
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.
Time frame: 30 days
Population: One participant in the control arm was lost to follow-up precluding outcome assessment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Subcutaneous Heparin | Number of Participants With Major Postoperative Bleeding | 4 Participants |
| Control | Number of Participants With Major Postoperative Bleeding | 2 Participants |
Primary
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.
Time frame: 30 days
Population: One participant in the control arm was lost to follow-up precluding outcome assessment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Subcutaneous Heparin | Number of Participants With Symptomatic Postoperative Fluid Collection | 10 Participants |
| Control | Number of Participants With Symptomatic Postoperative Fluid Collection | 9 Participants |
Primary
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).
Time frame: 30 days
Population: One participant in the control arm was lost to follow-up precluding outcome assessment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Subcutaneous Heparin | Number of Participants With Symptomatic Venous Thromboembolism | 2 Participants |
| Control | Number of Participants With Symptomatic Venous Thromboembolism | 5 Participants |
Secondary
Estimated Blood Loss During Surgery
The total recorded intraoperative estimated blood loss in milliliters reported at the end of the surgery.
Time frame: During surgery (usually between 2-3 hours of operative time)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Subcutaneous Heparin | Estimated Blood Loss During Surgery | 150 milliliters |
| Control | Estimated Blood Loss During Surgery | 200 milliliters |
Secondary
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.
Time frame: 30 days
Population: Only the subset receiving ultrasound are analyzed for this outcome.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Subcutaneous Heparin | Number of Participants With Occurrence of Any Venous Thromboembolism | 4 Participants |
| Control | Number of Participants With Occurrence of Any Venous Thromboembolism | 4 Participants |
Secondary
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.
Time frame: Over length of stay in hospital (usually 1 to 2 days)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Subcutaneous Heparin | Surgical Drain Output After Surgery | 95 milliliters |
| Control | Surgical Drain Output After Surgery | 100 milliliters |
Secondary
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).
Time frame: 30 days
Population: One participant in the control arm was lost to follow-up precluding outcome assessment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Subcutaneous Heparin | Surveillance Bias by Differential Use of Imaging as Assessed by Number of Participants Receiving Postoperative Diagnostic Imaging for Venous Thromboembolism Relative to Symptoms | 25 Participants |
| Control | Surveillance Bias by Differential Use of Imaging as Assessed by Number of Participants Receiving Postoperative Diagnostic Imaging for Venous Thromboembolism Relative to Symptoms | 31 Participants |