Enoxaparin for Blood Clot Prevention

(CRETE Trial)

Recruiting at 20 trial locations

Overseen By E. Vincent Faustino, MD, MHS

Age: < 18

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Yale University

Must not be taking: Antithrombotics

Disqualifiers: Bleeding, Surgery, Trauma, Coagulopathy, 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 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 28 days

258 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of the CRETE Studies is to investigate the newly identified age-dependent heterogeneity in the efficacy of enoxaparin in reducing the risk of central venous catheter-associated deep venous thrombosis in critically ill children.

Will I have to stop taking my current medications?

The trial requires that you are not currently receiving certain antithrombotic medications like LMWH, UFH, warfarin, or aspirin, except for UFH used to keep a vascular catheter open. If you are on these medications, you may need to stop them to participate.

What data supports the effectiveness of the drug Enoxaparin for blood clot prevention?

Enoxaparin has been shown to effectively prevent blood clots in patients who are not undergoing surgery but are very ill and have limited mobility. It works as well as another drug called unfractionated heparin, but with fewer side effects like bruising and liver issues. ^{1 2 3 4 5}

Is Enoxaparin generally safe for humans?

Enoxaparin, also known as Lovenox or Clexane, is generally considered safe for preventing blood clots, but it can cause side effects like skin reactions at the injection site, such as rash, pain, or redness. In rare cases, it may lead to more serious skin issues like tissue damage. Overall, it has a similar safety profile to other blood thinners, with fewer instances of certain side effects like liver enzyme increases. ^{1 3 4 6 7}

What makes the drug Enoxaparin unique for blood clot prevention?

Enoxaparin is unique because it is a low molecular weight heparin (a type of blood thinner) that can be administered once daily as a subcutaneous injection, making it more convenient than unfractionated heparin, which requires more frequent dosing. It is effective in preventing blood clots in both surgical and nonsurgical patients, and it has a lower risk of certain side effects like local hematomas compared to other similar treatments. ^{1 3 4 5 6}

Research Team

E. Vincent Faustino, MD, MHS

Principal Investigator

Associate Professor of Pediatrics, Yale School of Medicine

Eligibility Criteria

The CRETE Studies are for critically ill children from over 36 weeks gestational age to under 17 years old, who've had a central venous catheter placed in the last 24 hours. The trial excludes those with recent blood clots, bleeding issues, surgery or major trauma within the past week, certain coagulation disorders, severe kidney problems, heparin allergies or pork product sensitivities.

Inclusion Criteria

You cannot participate if you had a central venous catheter inserted less than 24 hours ago.

I am between 36 weeks corrected gestational age and under 17 years old.

My central venous catheter is in my neck or upper thigh.

Exclusion Criteria

I have not had surgery in the last week.

You have had a serious injury in the past week.

Current pregnancy or lactation

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either a prophylactic or therapeutic dose of enoxaparin based on age group, or usual care without placebo

Up to 28 days

Regular assessments using ultrasonography and clinical evaluations

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments for VTE and bleeding

36 hours after the last dose of enoxaparin

Exploratory Mechanistic Study

Biomarkers of thrombus formation mechanisms are compared between subjects with and without CADVT

Treatment Details

Interventions

• Enoxaparin

Trial Overview This study is testing whether Enoxaparin can prevent blood clots in young patients with central venous catheters. It focuses on how well it works across different ages and aims to reduce the risk of deep vein thrombosis associated with these catheters.

Participant Groups

Group I: Enoxaparin (Older Children Prophylactic) Experimental Treatment 1 Intervention

Prophylactic dose of enoxaparin for older children 1-17 years old.

Group II: Enoxaparin (Infants Therapeutic Low Anti-Xa Target) Experimental Treatment 1 Intervention

Therapeutic dose of enoxaparin for infants \<1 year old with anti-Xa target of 0.2-0.5 IU/mL.

Group III: Enoxaparin (Infants Therapeutic High Anti-Xa Target) Experimental Treatment 1 Intervention

Therapeutic dose of enoxaparin for infants \<1 year old with anti-Xa target of \>0.5-1 IU/mL.

Group IV: Control (Older Children) Active Control 1 Intervention

Usual care without placebo for older children 1-17 years old.

Group V: Control (Infants) Active Control 1 Intervention

Usual care without placebo for infants \<1 year old.

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

Approved in United States as Lovenox for:

• Deep vein thrombosis
• Pulmonary embolism
• Acute coronary syndromes

Approved in European Union as Clexane for:

• Deep vein thrombosis
• Pulmonary embolism
• Acute coronary syndromes
• Prevention of venous thromboembolism in surgical patients

Approved in Canada as Lovenox for:

• Deep vein thrombosis
• Pulmonary embolism
• Acute coronary syndromes

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

Children's Hospital of Illinois OSF Saint Francis Medical Center

Collaborator

Trials

1

Recruited

260+

Hassenfeld Children's Hospital

Collaborator

Trials

1

Recruited

260+

Children's Hospital Medical Center, Cincinnati

Collaborator

Trials

844

Recruited

6,566,000+

BJC HealthCare

Collaborator

Trials

4

Recruited

46,700+

Children's Healthcare of Atlanta

Collaborator

Trials

172

Recruited

108,000+

New York Presbyterian Hospital

Collaborator

Trials

77

Recruited

57,300+

Children's Hospital Colorado

Collaborator

Trials

121

Recruited

5,135,000+

Children's of Alabama

Collaborator

Trials

10

Recruited

3,000+

Penn State University

Collaborator

Trials

380

Recruited

131,000+

Findings from Research

Enoxaparin, a low molecular weight heparin, is effective for preventing venous thromboembolism (VTE) in nonsurgical patients with limited mobility due to acute illness, showing similar efficacy to unfractionated heparin but with the convenience of once-daily dosing.

Enoxaparin has a favorable tolerability profile, with lower incidences of local hematomas and increased liver enzymes compared to unfractionated heparin, making it a cost-effective option for short-term VTE prophylaxis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enoxaparin: a review of its use as thromboprophylaxis in acutely ill, nonsurgical patients. Siddiqui, MA., Wagstaff, AJ.[2018]

Enoxaparin, a low-molecular-weight heparin, significantly reduced lesion size by 30% and improved neurological function in stroke models when administered within 5 hours after a transient ischemic event.

In cases of permanent ischemia, enoxaparin reduced lesion size by 49% and also improved neurological outcomes, suggesting it has a wide therapeutic window and potential neuroprotective effects beyond its anticoagulant properties.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enoxaparin in experimental stroke: neuroprotection and therapeutic window of opportunity. Mary, V., Wahl, F., Uzan, A., et al.[2022]

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]

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]

Enoxaparin is effective for preventing deep venous thrombosis in patients undergoing hip or knee surgeries, but it can lead to severe bleeding complications, particularly in patients with head trauma, as demonstrated by a case of an elderly man who developed a delayed subdural hematoma after receiving the drug.

Given the risks associated with anticoagulation in trauma patients, alternative methods for venous thromboembolism prophylaxis, such as mechanical devices, should be considered to enhance patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Delayed subdural hematoma after receiving enoxaparin for prevention of thromboembolic events from high-risk surgery. Willard, RN., Muñiz, AE., Chuidian, F.[2016]

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]

In a study involving 200 patients undergoing major abdominal surgeries, both PDxane® and Clexane® were found to be equally effective in preventing venous thromboembolism (VTE), with no cases of VTE or life-threatening bleeding reported in either group.

PDxane® demonstrated a similar safety profile to Clexane®, with no significant differences in adverse effects, suggesting that PDxane® could be a cost-effective alternative for VTE prophylaxis in surgical patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of Efficacy and Safety of Two Different Enoxaparin Products in Prevention of Venous Thromboembolism Following Major Obstetric-gynecological Surgeries: An Open-label Randomized Clinical Trial. Abdolvand, M., Aleyasin, A., Javadi, MR., et al.[2020]

References

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

Enoxaparin: a review of its use as thromboprophylaxis in acutely ill, nonsurgical patients. [2018]

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

Enoxaparin in experimental stroke: neuroprotection and therapeutic window of opportunity. [2022]

3. Poland pubmed.ncbi.nlm.nih.gov

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

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

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

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

Delayed subdural hematoma after receiving enoxaparin for prevention of thromboembolic events from high-risk surgery. [2016]

6. 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]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Comparison of Efficacy and Safety of Two Different Enoxaparin Products in Prevention of Venous Thromboembolism Following Major Obstetric-gynecological Surgeries: An Open-label Randomized Clinical Trial. [2020]