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

• Sponsor: University of Utah (Other)
• Overall Status: Completed
• CT.gov ID: NCT03212365
• Collaborator: Stanford University (Other)
• Enrollment: 295
• Locations: 2
• Arms: 2
• Actual Duration (Months): 26.9
• Patients Per Site: 147.5
• Patients Per Site Per Month: 5.5

Study Details

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
• 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).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: Jul 3, 2017
• Actual Primary Completion Date: Jun 2, 2019
• Actual Study Completion Date: Oct 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Other: 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) [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) [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 [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 [90 days]

   Bleeding events requiring alteration in the course of care within 90 days of surgery

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

	Site	City	State	Country	Postal Code
1	Stanford University	Stanford	California	United States	94305
2	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)

• Study Protocol and Statistical Analysis Plan - Aug 6, 2020

More Information

Publications

None provided.

• Responsible Party: Christopher Pannucci, Assistant Professor, University of Utah
• ClinicalTrials.gov Identifier: NCT03212365
• Other Study ID Numbers: 100416
• First Posted: Jul 11, 2017
• Last Update Posted: Sep 16, 2020
• Last Verified: Aug 1, 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

Study Results

Participant Flow

Arm/Group Title	Fixed Dose	Variable Dose
Arm/Group Description	Participants will receive 40 mg enoxaparin twice daily Fixed dose: Participants will receive 40 mg enoxaparin twice daily	Participants will receive 0.5mg/kg enoxaparin twice daily Variable dose: Participants will receive 0.5mg/kg enoxaparin twice daily
Period Title: Overall Study
STARTED	151	144
COMPLETED	128	130
NOT COMPLETED	23	14

Baseline Characteristics

Arm/Group Title	Fixed Dose	Variable Dose	Total
Arm/Group Description	Participants will receive 40 mg enoxaparin twice daily Fixed dose: Participants will receive 40 mg enoxaparin twice daily	Participants will receive 0.5mg/kg enoxaparin twice daily Variable dose: Participants will receive 0.5mg/kg enoxaparin twice daily	Total of all reporting groups
Overall Participants	151	144	295
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	49.0 (15.6)	52.7 (14.8)	50.8 (15.3)
Sex/Gender, Customized (Count of Participants)
Female	81 53.6%	70 48.6%	151 51.2%
Male	70 46.4%	74 51.4%	144 48.8%
Race/Ethnicity, Customized (Count of Participants)
White	137 90.7%	135 93.8%	272 92.2%
African American	1 0.7%	0 0%	1 0.3%
Native American/Alaskan Native	1 0.7%	0 0%	1 0.3%
Hispanic or Latino	11 7.3%	8 5.6%	19 6.4%
Pacific Islander	1 0.7%	0 0%	1 0.3%
Other	0 0%	1 0.7%	1 0.3%
Region of Enrollment (participants) [Number]
United States	151 100%	144 100%	295 100%

Outcome Measures

1. Primary Outcome

Title	Avoidance of Under-anticoagulation (Peak aFXa <0.2 IU/mL)
Description	Avoidance of under-anticoagulation (peak aFXa <0.2 IU/mL)
Time Frame	Four hours following third enoxaparin dose

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Fixed Dose	Variable Dose
Arm/Group Description	Participants will receive 40 mg enoxaparin twice daily Fixed dose: Participants will receive 40 mg enoxaparin twice daily	Participants will receive 0.5mg/kg enoxaparin twice daily Variable dose: Participants will receive 0.5mg/kg enoxaparin twice daily
Measure Participants	128	130
Number [percentage of participants]	76.6 50.7%	79.9 55.5%

2. Primary Outcome

Title	Avoidance of Over-anticoagulation (Peak aFXa >0.4 IU/mL)
Description	Avoidance of over-anticoagulation (peak aFXa >0.4 IU/mL)
Time Frame	Four hours following third enoxaparin dose

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Fixed Dose	Variable Dose
Arm/Group Description	Participants will receive 40 mg enoxaparin twice daily Fixed dose: Participants will receive 40 mg enoxaparin twice daily	Participants will receive 0.5mg/kg enoxaparin twice daily Variable dose: Participants will receive 0.5mg/kg enoxaparin twice daily
Measure Participants	128	130
Number [percentage of participants]	82.2 54.4%	90.6 62.9%

3. Secondary Outcome

Title	Percentage of Participants With Venous Thromboembolism Events
Description	Any symptomatic venous thromboembolism events, including deep venous thrombosis or pulmonary embolus occurring within 90 days of surgery
Time Frame	90 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Fixed Dose	Variable Dose
Arm/Group Description	Participants will receive 40 mg enoxaparin twice daily Fixed dose: Participants will receive 40 mg enoxaparin twice daily	Participants will receive 0.5mg/kg enoxaparin twice daily Variable dose: Participants will receive 0.5mg/kg enoxaparin twice daily
Measure Participants	151	144
Number [percentage of patients]	0.66	0.69

4. Secondary Outcome

Title	Percentage of Patients With Bleeding Events
Description	Bleeding events requiring alteration in the course of care within 90 days of surgery
Time Frame	90 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Fixed Dose	Variable Dose
Arm/Group Description	Participants will receive 40 mg enoxaparin twice daily Fixed dose: Participants will receive 40 mg enoxaparin twice daily	Participants will receive 0.5mg/kg enoxaparin twice daily Variable dose: Participants will receive 0.5mg/kg enoxaparin twice daily
Measure Participants	151	144
Number [percentage of patients]	6.0	8.3

Adverse Events

Time Frame	90 days
Adverse Event Reporting Description	Study team performed chart review and made mandatory phone contact with patients at 90 days to identify adverse events.
Arm/Group Title	Fixed Dose		Variable Dose
Arm/Group Description	Participants will receive 40 mg enoxaparin twice daily Fixed dose: Participants will receive 40 mg enoxaparin twice daily		Participants will receive 0.5mg/kg enoxaparin twice daily Variable dose: Participants will receive 0.5mg/kg enoxaparin twice daily
All Cause Mortality
	Fixed Dose		Variable Dose
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/151 (0.7%)		0/144 (0%)
Serious Adverse Events
	Fixed Dose		Variable Dose
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/151 (0%)		0/144 (0%)
Other (Not Including Serious) Adverse Events
	Fixed Dose		Variable Dose
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/151 (0%)		0/144 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.