Efficacy and Safety for Different Regimen of VTE Pharmacoprophylaxis Among Severely Burn Patients

Comparison of the Efficacy and Safety for Different Regimen of Venous Thromboembolism Pharmacoprophylaxis Among Severely Burn Patients

This study aims to assess the feasibility and safety of VTE prophylaxis for 3 modality regimens (Unfractionated heparin 5000 U SQ q8 hours, Enoxaparin 40 mg SQ q24 hours or Enoxaparin 30 mg SQ q12 hours) in adult patients (≥18 y/o) with severely burn injuries (BSA≥20%) by measuring the bleeding incidence and VTE events.

Study Overview

• Status: Completed
• Conditions: Burns
• Intervention / Treatment: Drug: Unfractionated heparin 5000 U q8 hours; Drug: Enoxaparin 40 mg q24 hours; Drug: Enoxaparin 30 mg q12 hours

Detailed Description

This is a pilot , randomized control trial-Open label, prospective trial in tertiary academic hospitals for patient admitted to burn ICU for at least 24 hours of injury or transferred from other hospital(s) within 7 days of injury. Each patient admitted meets the inclusion criteria will be randomize by block randomization to either receive heparin 5000 units S.C. TID, enoxaparin 40 mg S.C. OD, or Enoxaparin 30 mg S.C. BID. VTE prophylaxis should be started within 36 hours of injury, if the patient is transferred from another facility, VTE prophylaxis should be started immediately unless contraindicated. All patients should undergo diagnostic ultrasound at baseline ( before starting the prophylaxis) to assess any presence of DVT and as clinically indicated for clinical suspicion for VTE thereafter until discharge, an urgent spiral CTA chest will be requested on clinical suspicion for PE. Anti Xa factor will be monitored at day 3, and weekly thereafter until discharge unless there is active bleeding or high clinical suspicion for bleeding. Will follow-up patient until discharge from ICU, developed VTE requiring treatment (switch to treatment dose), developed HIT or death.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Saudi Arabia
  • Riyadh, Saudi Arabia, 11426
    • King Abdulaziz Medical City

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Burn ICU admitted adult patients, age ≥ 18 years old.
• Body Mass Index of 18.5 to < 40 kg/m2.
• TBSA of 20% or more.

Exclusion Criteria:

• VTE history.
• Death within 24 hours of injury.
• Burn injuries combined with trauma requiring withholding pharmacoprophylaxis more than 48 hours.
• Coagulopathy (INR > 1.7, PTT> 2 times upper normal limit, platelet < 50k mm3)
• Patient with positive baseline US for VTE.
• Heparin induced thrombocytopenia (HIT).
• Active bleeding.
• Patients with CrCl of 30 ml/min or less.
• Patients using anticoagulation treatment dose for other indications.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Unfractionated Heparin (UFH) 5000 U q8 hours; Severely burn injuries (BSA≥20%) will receive Unfractionated Heparin (UFH) 5000 U q8 hours as pharmacological VTE prophylaxis	Drug: Unfractionated heparin 5000 U q8 hours; Severely burn injuries (BSA≥20%) will be assigned to 3 modality regimens of pharmacological VTE prophylaxis: Unfractionated heparin 5000 U SQ q8 hours, Enoxaparin 40 mg SQ q24 hours or Enoxaparin 30 mg SQ q12 hours.
Active Comparator: Enoxaparin 40 mg q24 hours; Severely burn injuries (BSA≥20%) will receive Enoxaparin 40 mg q24 hours as pharmacological VTE prophylaxis	Drug: Enoxaparin 40 mg q24 hours; Severely burn injuries (BSA≥20%) will be assigned to 3 modality regimens of pharmacological VTE prophylaxis: Unfractionated heparin 5000 U SQ q8 hours, Enoxaparin 40 mg SQ q24 hours or Enoxaparin 30 mg SQ q12 hours.
Active Comparator: Enoxaparin 30 mg q12 hours; Severely burn injuries (BSA≥20%) will receive Enoxaparin 30 mg q12 hours as pharmacological VTE prophylaxis	Drug: Enoxaparin 30 mg q12 hours; Severely burn injuries (BSA≥20%) will be assigned to 3 modality regimens of pharmacological VTE prophylaxis: Unfractionated heparin 5000 U SQ q8 hours, Enoxaparin 40 mg SQ q24 hours or Enoxaparin 30 mg SQ q12 hours.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of bleeding events (major and minor)	Daily assessment of major and minor Bleeding. Bleeding will classified into major and minor bleeding. Major bleeding defined as clinically overt bleeding associated with a fall ≥Hb 20g/L, transfusion of ≥2U PRBC or whole blood, retroperitoneal or intracranial bleeding or requiring urgent medical intervention. Minor bleeding defined as those not fulfilling the criteria of major or clinically significant bleeding.	Through study completion, an average of 2 years
Adverse effects in surgical outcomes (i.e. Graft loss, donor site morbidity, requirement of hemostatic intervention).	Daily assessment of donor site and graft site bleeding/failure. Graft site bleeding defined as bleeding at skin graft recipient site that requires premature wound exploration ( before 3 days postoperatively), bed side or operating room intervention to stop bleeding ( stitching, hemostatic agent or cauterization) with or without blood transfusion. Donor site bleeding/hematoma is any bleeding leading to a drop in hemoglobin > 2 grams, hemodynamic instability or bleeding requiring urgent transfusion. Graft failure due to hematoma that require re-grafting or more than 50% of the graft site. Enoxaparin should be held 12 hours and unfractionated heparin 3-4 hours before percutaneous tracheostomy OR epidural catheter if indicated.	Through study completion, an average of 2 years
Recruitment and consent rates	To assess the recruitment and consent rate to evaluate trial feasibility	Through study completion, an average of 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of VTE events (Symptomatic)	All patients participating in the study should undergo bilateral lower extremity duplex scan to rule out DVT at baseline before starting VTE prophylaxis and as clinically indicated for clinical suspicion for VTE thereafter until discharge from ICU, developing VTE incident or death. Urgent spiral CTA chest will be requested on clinical suspicion for PE.	Through study completion, an average of 2 years
Target anti Xa factor for enoxaparin or unfractionated heparin in severely burn patients.	Anti-Xa: Blood samples for Anti-Xa were obtained day 3 after patient is admitted to ICU (Plasma sample will be collected in blue tube "no citrate" ~ 5 mL/Test), then Anti-Xa obtained weekly thereafter until discharge. Anti-Xa obtained immediately 4 hours after administration of Enoxaparin and 3 hours after administration of unfractionated Heparin	Through study completion, an average of 2 years
Incidence of Heparin induced thrombocytopenia (HIT).		Through study completion, an average of 2 years
Number of days that patients stay in hospital	The length of an inpatient episode of care, calculated from the day of admission in hospital to day of discharge/death	Through study completion, an average of 2 years
Number of patients died within intensive care unit stay	The number of deaths of patients admitted to the intensive care unit (ICU), divided by the number of patient discharges from the ICU (including deaths and transfers).	Through study completion, an average of 2 years

Collaborators and Investigators

• Sponsor: King Abdullah International Medical Research Center

Study record dates

Study Major Dates

• Study Start (Actual): April 5, 2020
• Primary Completion (Actual): February 28, 2022
• Study Completion (Actual): February 28, 2022

Study Registration Dates

• First Submitted: January 3, 2022
• First Submitted That Met QC Criteria: February 11, 2022
• First Posted (Actual): February 14, 2022

Study Record Updates

• Last Update Posted (Actual): December 20, 2022
• Last Update Submitted That Met QC Criteria: December 17, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: Bleeding; Enoxaparin; VTE; Unfractionated Heparin; Severely burn; BSA≥20%
• Additional Relevant MeSH Terms: Wounds and Injuries; Burns; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Anticoagulants; Heparin; Enoxaparin; Calcium heparin; Enoxaparin sodium
• Other Study ID Numbers: RC18-400-R

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