Lovenox for Pregnancy Outcomes

Overseen By Kate Honeyfield

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: NorthShore University HealthSystem

Must not be taking: Anticoagulants

Disqualifiers: Major fetal anomaly, Kidney disease, 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 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 24 weeks

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether the drug Lovenox (Enoxaparin) can prevent complications in future pregnancies for women who previously experienced issues like early delivery, stillbirth, or severe high blood pressure during pregnancy. The trial examines if Lovenox can reduce the likelihood of these problems recurring, particularly when a condition in the placenta, known as maternal vascular malperfusion, was present in the earlier pregnancy. Participants will either receive standard care or take Lovenox once a day during their current pregnancy. Women who had a single baby born early, with low weight, or other issues in a past pregnancy and are currently pregnant with one baby might be suitable for this trial. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to important findings.

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 planning to use anticoagulants like warfarin, enoxaparin, or heparin during your current pregnancy.

Is there any evidence suggesting that Lovenox is likely to be safe for humans?

Research has shown that enoxaparin is generally safe for use during pregnancy. One study found it unexpectedly reduced the risk of pregnancy loss, a positive outcome. Another study demonstrated that a daily dose of either 40 mg or 80 mg of enoxaparin resulted in favorable pregnancy outcomes, with live birth rates of 69% and 83%, respectively.

Serious bleeding during pregnancy was rare. In a study of 624 pregnancies, only about 1.8% of women experienced serious bleeding, with just one case potentially linked to enoxaparin. At delivery, the rate was about 1.4%.

Overall, evidence suggests that a daily dose of 40 mg of enoxaparin is well-tolerated during pregnancy. While some risks exist, these studies generally indicate positive safety results for using enoxaparin in pregnant women. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for pregnancy outcomes?

Unlike the standard care for pregnancy outcomes, which typically involves monitoring and managing risk factors without additional medication, Lovenox (enoxaparin) offers a proactive approach by acting as a blood thinner. Researchers are excited about Lovenox because it targets blood clot prevention, potentially improving pregnancy outcomes for women at risk of complications due to blood clots. Its daily administration from the 12th week of pregnancy until the 36th week could help in reducing the risk of clot-related issues, offering a distinct advantage over traditional monitoring and management strategies.

What evidence suggests that Lovenox might be an effective treatment for adverse pregnancy outcomes?

Research has shown that enoxaparin, which participants in the enoxaparin group of this trial will receive, may improve pregnancy outcomes. One study demonstrated that using enoxaparin significantly increased successful births, with 84.3% of patients having healthy babies compared to 28.2% who did not use it. Another study found positive results, reporting live birth rates of 69% and 83% for different doses of enoxaparin. Additionally, enoxaparin reduced the risk of serious pregnancy issues like preeclampsia and fetal death. Overall, these findings suggest that enoxaparin could effectively prevent repeated negative pregnancy outcomes. ^{1 2 4 6 7}

Who Is on the Research Team?

Sunitha Suresh, MD

Principal Investigator

Endeavor Health

Are You a Good Fit for This Trial?

This trial is for individuals who had a prior pregnancy with complications like early delivery, very small babies, severe high blood pressure, or stillbirth. They must have had issues with the mother's blood vessels in the placenta and be currently pregnant with one baby before reaching 16 weeks and 6 days.

Inclusion Criteria

I am pregnant with one baby and less than 17 weeks along.

I had complications in a previous pregnancy due to placental issues.

Subjects with a previous unfavorable outcome in an earlier pregnancy, such as singleton preterm birth (less than 37 weeks), SGA infant (birthweight under 10th percentile), preeclampsia with serious characteristics, or stillbirth (fetal death after 20 weeks gestation) validated by an obstetrician.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to enoxaparin or control group. Enoxaparin group takes 40 mg daily from 12 weeks to 36 weeks gestational age.

24 weeks

Initial visit for randomization, follow-up visits at 1 week, 20-24 weeks, 32-34 weeks, and delivery

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of adverse pregnancy outcomes.

6 weeks postpartum

What Are the Treatments Tested in This Trial?

Interventions

• Lovenox

Trial Overview The study tests if Lovenox (enoxaparin) can prevent bad outcomes in new pregnancies for those who previously faced such issues due to problems with blood flow in the placenta. Participants are randomly chosen to receive this treatment or not.

How Is the Trial Designed?

Group I: Enoxaparin Group Experimental Treatment 1 Intervention

Participants in the enoxaparin group will be asked to take a dose of the enoxaparin once a day (40 mg daily) daily from 12 0/7 weeks and/or start of enrollment (whichever is later), and continue until 36 weeks gestational age, after which enoxaparin will be discontinued.

Group II: Control Group Active Control 1 Intervention

Participants in this group will have standard care as usual, with no additional medications.

Lovenox 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 syndrome
• Heart attacks
• Prevention of blood clots in pregnancy

Approved in European Union as Clexane for:

• Deep vein thrombosis
• Pulmonary embolism
• Acute coronary syndrome
• Heart attacks
• Prevention of blood clots in pregnancy

Approved in Canada as Lovenox for:

• Deep vein thrombosis
• Pulmonary embolism
• Acute coronary syndrome
• Heart attacks
• Prevention of blood clots in pregnancy

Who Is Running the Clinical Trial?

NorthShore University HealthSystem

Lead Sponsor

Trials

134

Recruited

740,000+

Endeavor Health

Lead Sponsor

Trials

135

Recruited

742,000+

Published Research Related to This Trial

Lovenox (enoxaparin sodium) is considered safe and effective for pregnant women needing either preventive or treatment anticoagulation, based on its use in various clinical scenarios.

However, it is not recommended for pregnant women with prosthetic heart valves, and caution is advised when using it before epidural anesthesia during labor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ACOG Committee Opinion: safety of Lovenox in pregnancy. [2009]

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]

In a study of 110 pregnant women receiving enoxaparin for prophylaxis, those monitored for anti-Xa levels had a higher final dose adjustment and significantly more term deliveries compared to those who were not monitored.

Women in the monitored group showed trends towards higher birth weights and fewer placenta-mediated complications, particularly noting that 28% of anti-Xa levels were below the prophylactic threshold in the second trimester, indicating the importance of monitoring during this period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of anti-Xa activity monitoring on the outcome of high-risk pregnancies treated with a prophylactic dose of low-molecular-weight heparin. Nasich, LL., Hoffman, R., Keren-Politansky, A., 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]

The use of selexipag, an oral prostacyclin receptor agonist, was successfully administered to a pregnant patient with severe pulmonary artery hypertension (PAH), allowing her to remain stable throughout her pregnancy and deliver a healthy baby.

Despite the initial success with selexipag, the patient unfortunately died 13 days after delivery due to worsening heart failure, highlighting the serious risks associated with PAH during and after pregnancy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of selexipag, a prostacyclin receptor analog, for treatment of severe pulmonary artery hypertension during pregnancy, a case report. Khan, A., Hubel, K., Brookfield, K., et al.[2023]

A 42-year-old woman with high-risk idiopathic pulmonary arterial hypertension (PAH) showed significant clinical and hemodynamic improvement after being treated with an off-label triple oral combination therapy that included selexipag, a phosphodiesterase-5 inhibitor, and an endothelin receptor antagonist.

This case suggests that oral combination therapies, like the one used in this patient, could be a viable alternative to parenteral prostacyclin analogues for high-risk PAH patients, warranting further investigation in controlled clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Upfront triple oral combination therapy including selexipag in a high-risk patient with idiopathic pulmonary arterial hypertension: a case report. Rossi, S., Pietrangelo, C., Pierdomenico, SD., et al.[2022]

Enoxaparin is supported by extensive evidence as a safe and effective anticoagulant for non-pregnant patients with prosthetic mechanical heart valves, based on numerous trials and expert opinions.

For pregnant patients without mechanical heart valves, enoxaparin is also effective for preventing and treating venous thromboembolism (VTE), but its use in pregnant women with mechanical heart valves requires more data before recommendations can be made.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

"Bridging" therapy with low molecular weight heparin in pregnant patients and patients with mechanical prosthetic heart valves. Groce, JB.[2018]

In the ENSURE-AF study involving 2199 patients, edoxaban demonstrated similar efficacy to enoxaparin-warfarin in preventing serious cardiovascular events after electrical cardioversion for non-valvular atrial fibrillation, with fewer events reported in the edoxaban group (0.5% vs. 0.9% for VKA experienced patients).

The safety profile of edoxaban was comparable to that of enox-warf, with no significant differences in major bleeding rates or clinically relevant nonmajor bleeding, regardless of whether patients were experienced or naïve to vitamin K antagonists.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Edoxaban versus warfarin in vitamin K antagonist experienced and naïve patients from the edoxaban versus warfarin in subjects undergoing cardioversion of atrial fibrillation (ENSURE-AF) randomised trial. Kozieł, M., Al-Saady, N., Hjortshøj, SP., et al.[2021]

A novel approach using peripheral extracorporeal membrane oxygenation (ECMO) combined with upfront therapy, including intravenous epoprostenol, effectively treated a female patient with idiopathic pulmonary arterial hypertension (IPAH) after childbirth.

This treatment allowed the patient to transition successfully from intravenous epoprostenol to oral selexipag, highlighting the potential of ECMO as a bridging therapy for patients with IPAH who are unable to stand or recover on their own.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Addition of a bilateral access form of peripheral extracorporeal membrane oxygenation rescued a patient with idiopathic pulmonary arterial hypertension who developed circulatory collapse immediately after childbirth. Adachi, S., Shimokata, S., Yoshida, M., et al.[2020]

In a Phase II study involving 28 Japanese patients with chronic thromboembolic pulmonary hypertension (CTEPH), selexipag treatment led to a significant decrease in pulmonary vascular resistance (PVR) for patients not using other pulmonary vasodilators, indicating its potential efficacy in improving pulmonary hemodynamics.

Although the primary endpoint of overall PVR change did not reach statistical significance when comparing selexipag to placebo, the treatment showed positive effects on total pulmonary resistance and cardiac index, suggesting it may still offer benefits in managing CTEPH.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selexipag for Chronic Thromboembolic Pulmonary Hypertension in Japanese Patients - A Double-Blind, Randomized, Placebo-Controlled, Multicenter Phase II Study. Tanabe, N., Fukuda, K., Matsubara, H., et al.[2021]

In a study of 24 pediatric patients with pulmonary hypertension, selexipag was found to be a safe adjunctive therapy, with 91.7% of patients remaining on dual pulmonary hypertension therapy after six months.

While there were some improvements in heart function and pulmonary pressure after 12 months of treatment, these changes were not statistically significant, indicating the need for further research to better understand the long-term benefits of selexipag in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Canadian, retrospective, multicenter experience with selexipag for a heterogeneous group of pediatric pulmonary hypertension patients. Youssef, D., Richards, S., Lague, S., et al.[2023]

Lovenox (enoxaparin sodium) is considered safe and effective for pregnant women needing either preventive or treatment anticoagulation, based on its use in various clinical scenarios.

However, it is not recommended for pregnant women with prosthetic heart valves, and caution is advised when using it before epidural anesthesia during labor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ACOG committee opinion. Safety of Lovenox in pregnancy. Number 276, October 2002. Committee on Obstetric Practice. [2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6979442/

Safety and Efficacy of Enoxaparin in Pregnancy: A Systematic ... When compared to aspirin, risk of bleeding was 7% lower with enoxaparin monotherapy and 5% lower with enoxaparin plus aspirin. These results were not ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/14712967/

Prophylactic and therapeutic enoxaparin during pregnancy Conclusions: In the present series, prophylactic and therapeutic enoxaparin treatment during pregnancy was effective and safe. Studies are required to determine ...

3. ajog.org ajog.org/article/S0002-9378(04)01069-5/fulltext

Efficacy of enoxaparin for improving pregnancy outcomes ... Results. Prophylaxis with enoxaparin significantly increased the rate of live birth (84.3% vs 28.2% for 40 mg/day, 78.3% vs 28.3% for ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S1538783622130345

Efficacy and safety of two doses of enoxaparin in women ... Treatment with enoxaparin 40 mg day −1 or 80 mg day −1 resulted in favorable pregnancy outcomes with live birth rates of 69% and 83%, respectively.

5. jogcr.com jogcr.com/article_710793_595608d4870d8b0ee4b3f1dea36fb5d3.pdf

Effect of Enoxaparin on Live Birth Rate in Patients with ... Both the control and treatment groups did not experience adverse pregnancy outcomes, such as preeclampsia, placental abruption, hemorrhage, or fetal death.

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/11762651/

a retrospective study of enoxaparin safety in 624 pregnancies Serious maternal haemorrhage occurred in 11 cases during pregnancy (1.8%), one being reasonably related to enoxaparin, and in nine cases at delivery (1.4%), all ...

7. ashpublications.org ashpublications.org/blood/article/125/14/2200/33843/Enoxaparin-for-prevention-of-unexplained-recurrent

Enoxaparin for prevention of unexplained recurrent miscarriage Enoxaparin use at a daily dose of 40 mg was safe during early pregnancy. Our trial was designed to detect a minimal clinically important difference of 10% in ...