Enoxaparin Dosing Regimens for Blood Clots

Overseen By Laura Nguyen

Age: Any Age

Sex: Any

Trial Phase: Phase 4

Sponsor: Oregon Health and Science University

Must be taking: Enoxaparin

Must not be taking: Other anticoagulants

Disqualifiers: Intracranial hemorrhage, Renal failure, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 90 days

606 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are already receiving a therapeutic dose of enoxaparin or other forms of anticoagulation.

What data supports the effectiveness of the drug Enoxaparin Sodium Injection for blood clots?

Research shows that Enoxaparin, also known as Lovenox, is effective in preventing blood clots during hemodialysis, with nearly half of the patients maintaining a low dose successfully. Additionally, it is widely used to prevent and treat conditions like deep vein thrombosis and pulmonary embolism, which are types of blood clots. ^{1 2 3 4 5}

Is Enoxaparin generally safe for humans?

Enoxaparin, also known as Lovenox or Clexane, is generally safe for humans, but it can cause skin reactions like redness or bruising at the injection site, and in rare cases, more severe skin damage. High doses can lead to serious bleeding, so it's important to follow dosing instructions carefully. ^{2 3 4 6 7}

How does the drug Enoxaparin differ from other treatments for blood clots?

Enoxaparin is a low-molecular-weight heparin (LMWH) that is unique because it is given as a subcutaneous injection and works by enhancing the action of antithrombin to inhibit several clotting factors, which helps prevent blood clots. Compared to unfractionated heparin (UFH), it has a more predictable pharmacodynamic profile and has shown greater efficacy in certain conditions like ST-segment elevation myocardial infarction (STEMI). ^{1 2 3 5 8}

What is the purpose of this trial?

The risk of developing a blood clot occurs in up to 60% of all critical care patients. Many times enoxaparin (or Lovenox) is given to patients who are at a higher risk of developing clots in their legs or lungs. There are two standard doses of enoxaparin that are recommended by the drug companies. These two doses have never been directly compared in trauma, general, and vascular surgery patients. The purposes of this study are: 1. to compare the development of blood clots in patients receiving 30mg twice daily of enoxaparin compared to patients receiving 40mg once daily of enoxaparin. 2. to determine if there is higher risk of bleeding complications in patients receiving 30mg twice daily of enoxaparin compared to patients receiving 40mg once daily. Patients enrolled into the study will be randomized to receive enoxaparin, 30mg twice daily or enoxaparin, 40mg once daily. Patients will then be monitored for signs and symptoms of blood clots. At the time of discharge (or before, if medically indicated), an ultrasound test will be performed to look for blood clots in the patient's legs. The investigators will compare incidence of blood clots formed between the 2 groups of patients to determine if one dose of enoxaparin relates to a lower rate of blood clots in critically ill patients. The investigators will also compare the incidence of bleeding complications between the 2 groups.

Research Team

Martin A Schreiber, MD

Principal Investigator

Oregon Health and Science University

Eligibility Criteria

This trial is for patients over 15 years old who are at risk of blood clots and need preventive treatment with enoxaparin after trauma or surgery. It's not for those who can't consent, already on a full dose of enoxaparin, using other anticoagulants, have kidney failure needing special doses, or have bleeding in the brain.

Inclusion Criteria

I am in the hospital and need preventive blood clot medication.

I am older than 15 years.

I am currently admitted under the care of a trauma or surgical team.

Exclusion Criteria

Unable to obtain consent from patient or authorized representative

I am currently on blood thinners.

I have had bleeding in my brain.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive enoxaparin, either 30 mg twice daily or 40 mg once daily, and are monitored for signs and symptoms of blood clots.

Up to 90 days

Daily monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment, including weekly ultrasound duplex examinations of the lower extremities.

4 weeks

Weekly visits

Treatment Details

Interventions

• Enoxaparin Sodium Injection

Trial Overview The study compares two dosing schedules of enoxaparin: one group receives 30 mg twice daily while another gets 40 mg once daily. The goal is to see which dosage better prevents blood clots without increasing bleeding risks in critical care patients.

Participant Groups

Group I: Enoxaparin Sodium Injection 30 mg BID Active Control 1 Intervention

Subjects are randomized to receive 30 mg twice daily of enoxaparin.

Group II: Enoxaparin Sodium Injection 40 mg QD Active Control 1 Intervention

Subjects are randomized to receive 40 mg once daily of enoxaparin.

Enoxaparin Sodium Injection is already approved in United States, European Union for the following indications:

Approved in United States as Lovenox for:

• Prevention of deep vein thrombosis
• Treatment of acute deep vein thrombosis with or without pulmonary embolism
• Prevention of ischemic complications in unstable angina and non-Q-wave myocardial infarction

Approved in European Union as Clexane for:

• Prevention of deep vein thrombosis
• Treatment of acute deep vein thrombosis with or without pulmonary embolism
• Prevention of ischemic complications in unstable angina and non-Q-wave myocardial infarction

Who Is Running the Clinical Trial?

Oregon Health and Science University

Lead Sponsor

Trials

1,024

Recruited

7,420,000+

Findings from Research

In a multicenter trial involving 72 hemodialysis patients, an initial dose of 0.5 mg/kg of enoxaparine effectively prevented clotting in nearly half of the patients during dialysis sessions without any complications or side effects.

The study found that 59% of patients required a higher dose (between 0.6 and 0.9 mg/kg) to maintain effective anticoagulation, suggesting that individual patient factors may influence the optimal dosage for preventing thrombotic events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Optimization of enoxaparin dose in the prevention of coagulation in the circuits of hemodialysis: results of a multicenter study]. Reach, I., Thébaud, HE., Dupuy, CA., et al.[2006]

Lovenox (Enoxaparin) is an effective anticoagulant used to prevent and treat venous thromboembolism events, administered via subcutaneous injection.

While common side effects like skin reactions typically occur at the injection site, new studies indicate that severe skin and tissue necrosis can also develop at a distance from the injection site, highlighting a potential safety concern.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lovenox Induced Tissue Necrosis, a Case Report and Literature Review. Issa, AA., Simman, R.[2020]

A patient received an accidental subcutaneous injection of 450 mg Enoxaparin sodium after complex cardiac surgery, leading to severe coagulopathy.

The situation required the transfusion of allogenic blood products, highlighting the risks associated with high doses of anticoagulants like Enoxaparin in postoperative care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Hemorrhage after accidental overdosage of enoxaparin: monitoring and therapy]. Weber, CF., Meybohm, P., Kramer, S., et al.[2014]

Enoxaparin sodium is crucial for treating and preventing thromboembolic complications in COVID-19, but the rise of generic versions has raised concerns about quality and safety, prompting stricter regulatory measures.

The U.S. Pharmacopoeia now requires specific molecular weight determination and the presence of a unique structural feature in generic enoxaparin, allowing for potential approval without animal or human testing if strong analytical similarities are demonstrated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Scientific considerations in the regulatory approval of generic (or biosimilar) version of enoxaparin sodium - A lifesaving carbohydrate polymer. Iqbal, Z., Sadaf, S.[2023]

The Heptest method was used to analyze the effects of two low-molecular-weight heparin (LMWH) drugs, Enoxaparin sodium from Russia and Clexane from France, on blood clotting times, showing that both drugs had similar effects on human plasma.

The study found that Enoxaparin sodium was comparable in efficacy to Clexane, indicating that the domestic version may be a viable alternative to the original drug.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative Analysis of Two Enoxaparin Sodium Drugs by Heptest. Berkovskii, AL., Sergeeva, EV., Chernobrovkin, MG., et al.[2023]

A preclinical study involving 80 rats showed that the biosimilar enoxaparin product 'Enoxa' has a comparable toxicity profile to the reference drug 'Lovenox' at therapeutic and toxic doses, indicating potential safety for use.

Both 'Enoxa' and 'Lovenox' exhibited few adverse effects at a toxic dose of 20 mg/kg/day, with significant mortality only observed at much higher doses, suggesting that 'Enoxa' may be a safe alternative to the original enoxaparin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative subcutaneous repeated toxicity study of enoxaparin products in rats. Kobbi, Z., Kraiem, H., Benlasfar, Z., et al.[2017]

Enoxaparin, administered at a subcutaneous dose of 40 mg daily, is highly effective for antithrombotic prophylaxis after total hip replacement surgery.

The use of enoxaparin showed minor side effects, indicating a good safety profile for patients undergoing this procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Enoxaparin (clexane) in the prevention of thromboembolism after total hip replacement]. Babiak, I., Jabłoński, T., Serafin, J.[2014]

Enoxaparin, a low-molecular-weight heparin, has been approved for use in patients with ST-segment myocardial infarction (STEMI) and has shown to be significantly more effective than unfractionated heparin (UFH) in reducing the incidence of all-cause mortality and recurrent nonfatal myocardial infarction, as demonstrated in the ExTRACT-TIMI 25 trial with a follow-up of 1 year.

While enoxaparin was associated with a higher frequency of bleeding compared to UFH, it still provided a net clinical benefit, indicating its efficacy in preventing serious cardiovascular events in STEMI patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enoxaparin: a review of its use in ST-segment elevation myocardial infarction. Carter, NJ., McCormack, PL., Plosker, GL.[2021]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

[Optimization of enoxaparin dose in the prevention of coagulation in the circuits of hemodialysis: results of a multicenter study]. [2006]

2. United States pubmed.ncbi.nlm.nih.gov

Lovenox Induced Tissue Necrosis, a Case Report and Literature Review. [2020]

3. Germany pubmed.ncbi.nlm.nih.gov

[Hemorrhage after accidental overdosage of enoxaparin: monitoring and therapy]. [2014]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Scientific considerations in the regulatory approval of generic (or biosimilar) version of enoxaparin sodium - A lifesaving carbohydrate polymer. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Comparative Analysis of Two Enoxaparin Sodium Drugs by Heptest. [2023]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Comparative subcutaneous repeated toxicity study of enoxaparin products in rats. [2017]

7. Poland pubmed.ncbi.nlm.nih.gov

[Enoxaparin (clexane) in the prevention of thromboembolism after total hip replacement]. [2014]

8. New Zealand pubmed.ncbi.nlm.nih.gov

Enoxaparin: a review of its use in ST-segment elevation myocardial infarction. [2021]