Minimization of Bleeding Related Adverse Drug Events in Plastic & Reconstructive Surgery

• ClinicalTrials.gov Identifier: NCT03212365
• Recruitment Status: Completed
• First Posted: July 11, 2017
• Results First Posted: September 16, 2020
• Last Update Posted: September 16, 2020
• Sponsor: University of Utah
• Collaborator: Stanford University
• Information provided by (Responsible Party): Christopher Pannucci, University of Utah

Study Description

Brief Summary:

Plastic and reconstructive surgeons consistently create large, raw surfaces as part of their operative procedures. Thus, plastic & reconstructive surgery patients are among those at highest risk for anticoagulant-associated bleeding adverse drug events (ADEs). This study seeks to optimize both the safety and effectiveness of post-operative enoxaparin by comparing aFXa levels, bleeding events, and VTE events among plastic & reconstructive surgery patients randomized to receive two different enoxaparin dose regimens.

Condition or disease	Intervention/treatment	Phase
Venous Thromboembolism; Deep Venous Thrombosis; Pulmonary Embolus; Reconstructive Surgery	Drug: Fixed dose; Drug: Variable dose	Phase 2

Detailed Description:

Plastic and reconstructive surgeons consistently create large, raw surfaces as part of their operative procedures. Thus, plastic & reconstructive surgery patients are among those at highest risk for anticoagulant-associated bleeding adverse drug events (ADEs). Our preliminary data has shown that a fixed, or "one size fits all" dose of enoxaparin, an anticoagulant, can allow a high proportion of patients to have appropriately thinned blood, measured by anti-Factor Xa (aFXa) levels. Patients with adequate aFXa levels are known to have significantly decreased venous thromboembolism risk (VTE), which is desirable. However, 30% of patients who receive fixed dose enoxaparin have blood that is too thin. Patients who are over-anticoagulated are significantly more likely to have ADEs including bleeding requiring return to the operating room, need for blood transfusion, or death. The optimal way to dose enoxaparin to minimize ADEs remains unknown. This study seeks to optimize both the safety and effectiveness of post-operative enoxaparin by comparing aFXa levels, bleeding events, and VTE events among plastic & reconstructive surgery patients randomized to receive two different enoxaparin dose regimens.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 295 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Patients will be randomized into one of two groups (enoxaparin 40mg twice daily or enoxaparin 0.5mg/kg twice daily, rounded to the nearest milligram).
• Masking: Double (Participant, Investigator)
• Primary Purpose: Other
• Official Title: Minimization of Bleeding Related Adverse Drug Events in Plastic & Reconstructive Surgery Patients Randomized to Different Postoperative Anticoagulant Regimens
• Actual Study Start Date: July 3, 2017
• Actual Primary Completion Date: June 2, 2019
• Actual Study Completion Date: October 1, 2019

Arms and Interventions

Arm	Intervention/treatment
Fixed Dose; Participants will receive 40 mg enoxaparin twice daily	Drug: Fixed dose; Participants will receive 40 mg enoxaparin twice daily
Experimental: Variable Dose; Participants will receive 0.5mg/kg enoxaparin twice daily	Drug: Variable dose; Participants will receive 0.5mg/kg enoxaparin twice daily

Outcome Measures

Primary Outcome Measures :

1. Avoidance of Under-anticoagulation (Peak aFXa <0.2 IU/mL) [ Time Frame: Four hours following third enoxaparin dose ]
   Avoidance of under-anticoagulation (peak aFXa <0.2 IU/mL)
2. Avoidance of Over-anticoagulation (Peak aFXa >0.4 IU/mL) [ Time Frame: Four hours following third enoxaparin dose ]
   Avoidance of over-anticoagulation (peak aFXa >0.4 IU/mL)

Secondary Outcome Measures :

1. Percentage of Participants With Venous Thromboembolism Events [ Time Frame: 90 days ]
   Any symptomatic venous thromboembolism events, including deep venous thrombosis or pulmonary embolus occurring within 90 days of surgery
2. Percentage of Patients With Bleeding Events [ Time Frame: 90 days ]
   Bleeding events requiring alteration in the course of care within 90 days of surgery

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• receiving plastic and reconstructive surgery under general anesthesis
• Expected post-operative stay of 2 days or more

Exclusion Criteria:

• Contraindication to use of enoxaparin
• intracranial bleeding/stroke
• Hematoma or bleeding disorder
• Heparin-induced thrmbocytopenia positive
• Creatinine clearance less than or equal to 30 mL/min
• Serum creatinine greater than 1.6 mg/dL
• epidural anesthesia
• patients placed on non-enoxaparin chemoprophylaxis regimens
• gross weight exceeding 150kg

Contacts and Locations

Locations

United States, California

Stanford University

Stanford, California, United States, 94305

United States, Utah

University of Utah

Salt Lake City, Utah, United States, 84132

Sponsors and Collaborators

University of Utah

Stanford University

Investigators

• Principal Investigator: Christopher Puccini, MD; University of Utah

  Study Documents (Full-Text)

Documents provided by Christopher Pannucci, University of Utah:

Study Protocol and Statistical Analysis Plan  [PDF] August 6, 2020

More Information

• Responsible Party: Christopher Pannucci, Assistant Professor, University of Utah
• ClinicalTrials.gov Identifier: NCT03212365
• Other Study ID Numbers: 100416
• First Posted: July 11, 2017
• Results First Posted: September 16, 2020
• Last Update Posted: September 16, 2020
• Last Verified: August 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Pulmonary Embolism; Thrombosis; Thromboembolism; Venous Thromboembolism; Venous Thrombosis; Drug-Related Side Effects and Adverse Reactions; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Chemically-Induced Disorders; Embolism; Lung Diseases; Respiratory Tract Diseases