Enoxaparin Versus Placebo for Venous Thromboembolism Prevention in Low Risk Cancer Patients After Surgical Procedures: a Randomized, Double Blind, Placebo Controlled Clinical Trial Pilot Study

NCT03988231 | Withdrawn Phase 4 DMC

• 1 other identifier: IRB_00121324
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

Post-surgical bleeding is a major source of morbidity in cancer patients, and ramifications can include need for transfusion, increased length of hospital stay, unexpected return to the operating room, or even death. Current guidelines support that all cancer patients who require surgical procedures receive post-operative blood thinners to minimize risk for blood clots in the legs or lungs, known as venous thromboembolism (VTE), but these medications have an unfavorable risk/benefit relationship among patients at low risk for VTE. The proposed work will pilot a randomized, double blind, placebo controlled trial to critically examine the role of de-implementation of current guidelines that mandate blood thinning medications among cancer patients at low risk for VTE who require surgical procedures; the pilot trial will allow optimization of the design of a future pragmatic multicenter trial, which ultimately would maximize patient safety after surgical procedures for cancer.

Conditions

Venous Thromboembolism; Bleeding as Surgical Complication (Treatment); Deep Venous Thrombosis; Pulmonary Embolism

Outcome Measures

Primary Outcomes (2)

• 90-day symptomatic venous thromboembolism

  Symptomatic VTE will include 1) any deep venous thrombosis event, including upper limb, lower limb, or central veins (inferior vena cava, portal vein, etc) that is confirmed with imaging including but not limited to duplex ultrasound, CT scan, or venogram and/or 2) any pulmonary embolus event that is confirmed with imaging, including but not limited to CT scan, venogram, or V/Q scan and/or 3) any autopsy-proven VTE and/or 4) 90-day mortality in which VTE cannot be excluded (eg PEA arrest with no autopsy performed).

  90 days

• 90-day clinically relevant bleeding

  1. Symptomatic or clinically overt bleeding that is associated with one or more of a) transfusion of ≥2 units of blood, b) hemoglobin decrease of \>2g/dL, or c) need for reoperation or invasive intervention such as wound opening or percutaneous drainage procedure and/or 2. Symptomatic or clinically overt bleeding at a critical anatomic site, including intracranial, intraspinal, intraocular, retroperitoneal, intraarticular, pericardial, or within a muscle compartment causing compartment syndrome 3. Fatal bleeding, in which the bleeding event directly contributes to death or causes clinical deterioration leading to death 4. In addition, we include clinically overt bleeding in which the surgeon chooses to discontinue study drug (enoxaparin versus placebo) prior to hospital discharge as a bleeding event.

  90 days

Study Arms (2)

Enoxaparin 40mg once daily

ACTIVE COMPARATOR

All patients will have enoxaparin prophylaxis or placebo initiated at 8 hours after surgery. Prophylaxis or placebo will be provided every 24 hours and will be continued for the duration of inpatient stay.

Drug: Receipt of enoxaparin

Placebo

PLACEBO COMPARATOR

All patients will have enoxaparin prophylaxis or placebo initiated at 8 hours after surgery. Prophylaxis or placebo will be provided every 24 hours and will be continued for the duration of inpatient stay.

Drug: Placebo

Interventions

Receipt of enoxaparin DRUG

Patients will be randomized to enoxaparin 40mg once daily versus saline placebo at 8 hours after surgery and continued for the duration of inpatient stay.

Enoxaparin 40mg once daily

Placebo DRUG

Patients will be randomized to enoxaparin 40mg once daily versus saline placebo at 8 hours after surgery and continued for the duration of inpatient stay.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult (age≥18) patients
• Surgical procedure under general anesthesia
• Caprini score ≤6
• Expected post-operative stay will be at least 23 hours (these are the patients for whom current guidelines mandate provision of chemical prophylaxis, but for whom current clinical practice demonstrates equipoise.)

You may not qualify if:

• Contraindication to use of enoxaparin
• Intracranial bleeding/stroke
• Hematoma or bleeding disorder
• Heparin-induced thrombocytopenia positive
• Creatinine clearance ≤ 30mL/min
• Serum creatinine \>1.6mg/dL
• Planned epidural anesthesia
• Patients with platelet count \<50k/uL will be excluded only with "a positive in vitro test for anti-platelet antibody in the presence of enoxaparin sodium," per the enoxaparin package insert.

Sponsors & Collaborators

• University of Utah: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

MeSH Terms

Conditions

Venous Thromboembolism; Venous Thrombosis; Pulmonary Embolism

Condition Hierarchy (Ancestors)

Thromboembolism; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Thrombosis; Lung Diseases; Respiratory Tract Diseases; Embolism

Study Officials

• Christopher Pannucci, MD MS

  University of Utah

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Randomized, double blind, placebo controlled trial
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: June 13, 2019
• First Posted: June 17, 2019
• Study Start: July 1, 2021
• Primary Completion: June 1, 2022
• Study Completion: June 1, 2023
• Last Updated: October 8, 2021

Record last verified: 2021-09