Enoxaparin for Blood Clot Prevention

(CRETE Trial)

Recruiting at 23 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if enoxaparin, an anticoagulant medication, can prevent serious blood clots in critically ill children with central venous catheters. Researchers are examining the treatment's effectiveness, which may vary with age. The trial includes different groups: older children might receive usual care or a preventive dose, while infants could receive various therapeutic doses. Children who had a central venous catheter placed in the neck or thigh within the last 24 hours may qualify for this study. As a Phase 2, Phase 3 trial, this study is essential for evaluating the treatment's effectiveness in a larger group and is a key step before potential FDA approval.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that enoxaparin is generally safe for children, but some important details require attention. For older children, studies suggest that enoxaparin can be safely used to prevent blood clots. One study found that administering enoxaparin once a day might be a good option for these children. However, the official drug label states that its safety in children is not fully established, and it is not approved for infants.

For infants, enoxaparin appears to be well-tolerated. Research indicates that preterm infants can handle enoxaparin without major issues. They might need a higher dose to achieve the desired effect, but researchers found it safe to use at these levels. For infants under 2 months, dosing is usually based on weight and adjusted to reach the right anti-Xa target, which measures how well the drug is working.

Overall, enoxaparin has been used in children, but close monitoring is important. Studies have shown it can be safe, but not all agree completely. Always consult a healthcare provider to understand the risks and benefits. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about using Enoxaparin for preventing blood clots in kids and infants because it offers a tailored approach. Unlike standard treatments, which often use a one-size-fits-all dosage, Enoxaparin provides specific prophylactic doses for older children and therapeutic doses with varying anti-Xa targets for infants. This means the treatment can be more precisely adjusted to a child’s age and specific needs, potentially improving safety and effectiveness in preventing clots.

What evidence suggests that enoxaparin could be effective for preventing blood clots in critically ill children?

Research has shown that enoxaparin can help prevent blood clots in children. In this trial, older children may receive a prophylactic dose of enoxaparin, which studies indicate effectively reduces the risk of blood clots, with results similar to other treatments. For infants, this trial will test different therapeutic doses of enoxaparin. Past studies showed that about 56% of infants reached the desired level of clot prevention. Overall, enoxaparin is well-regarded for preventing deep vein thrombosis (DVT) across various age groups. ^{1 3 6 7 8}

Who Is on the Research Team?

E. Vincent Faustino, MD, MHS

Principal Investigator

Associate Professor of Pediatrics, Yale School of Medicine

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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 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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7671020/

Evaluation of a Pediatric Enoxaparin Dosing Protocol and ... The current enoxaparin dosing nomogram is only successful at achieving a therapeutic anti-Xa concentration (0.5–1.0 unit/mL) 55.8% of the time.

2. withpower.com withpower.com/trial/phase-2-and-3-venous-thrombosis-2022-4617e

Enoxaparin for Blood Clot Prevention (CRETE Trial) Enoxaparin, administered at a subcutaneous dose of 40 mg daily, is highly effective for antithrombotic prophylaxis after total hip replacement surgery. The use ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12359062/

Impact of Pharmacist-To-Dose Enoxaparin in Pediatric ... Enoxaparin boasts a longer half-life, elevated subcutaneous bioavailability, and a reduced risk of heparin-induced thrombocytopenia in contrast ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0049384824003463

Optimizing therapeutic enoxaparin in preterm neonates ... Preterm neonates appear to require a median enoxaparin dose of 2 mg/kg subcutaneously every 12 h to achieve therapeutic anti-Xa levels.

5. pharmacypractice.org pharmacypractice.org/index.php/pp/article/download/2948/1178/10666

Systematic review and meta-analysis of individualized ... Various clinical outcomes were assessed across the studies. These outcomes included time to therapeutic anti-Xa levels, bleeding events ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3018183/

Effects of Age and Weight-Based Dosing of Enoxaparin on ... The recommended dose of enoxaparin is 1.5 mg/kg for patients < 2 months of age and 1 mg/kg for patients ≥ 2 months of age, given twice daily subcutaneously.

7. jthjournal.org jthjournal.org/article/S1538-7836(22)04032-6/fulltext

Lack of anti‐factor Xa assay standardization results in ... These data support a pediatric randomized controlled clinical trial comparing the safety and efficacy of enoxaparin weight‐based dosing with or without dose ...

8. thrombosisresearch.com thrombosisresearch.com/article/S0049-3848(13)00275-2/pdf

Pharmacokinetic analysis of enoxaparin in a term neonate ... Recommended target anti-Xa levels for therapeutic enoxaparin are 0.5-1.0 Units/ml at 4-6 hours post-dose, and 0.1-0.3 Units/ml for prophylactic ...