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

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

What data supports the effectiveness of the drug Lovenox for pregnancy outcomes?

Research indicates that Lovenox (enoxaparin sodium) is safe and effective for pregnant women who need blood-thinning treatment, except for those with prosthetic heart valves. It is used to prevent and treat blood clots, which can be a risk during pregnancy. ^{1 2 3 4 5}

Is Lovenox (Enoxaparin) generally safe for use in humans, including during pregnancy?

Lovenox (Enoxaparin) is generally considered safe for pregnant women who need it, but it should be used carefully in those with prosthetic heart valves and before certain pain relief procedures during labor. Some skin reactions, like redness or bruising, can occur at the injection site, and in rare cases, more severe skin issues may develop. ^{1 2 3 6 7}

How does the drug Lovenox differ from other treatments for pregnancy outcomes?

Lovenox (Enoxaparin) is a type of blood thinner that works by preventing the formation of blood clots, which can be crucial during pregnancy to prevent complications. Unlike some other treatments, it is administered via injection, which can be more effective for certain conditions compared to oral medications. ^{8 9 10 11 12}

What is the purpose of this trial?

The goal of this randomized clinical trial is to evaluate if we can use placental pathology in a prior pregnancy which had an adverse outcome, such as early delivery, stillbirth, a baby born smaller than expected, or severe forms of high blood pressure during pregnancy, to guide treatment in the subsequent pregnancy and reduce risk of recurrent adverse pregnancy events. The main questions it aims to answer are: * Whether enoxaparin prevents recurrent adverse pregnancy outcomes among patients with a prior adverse pregnancy outcome that occurred in the setting of maternal vascular malperfusion (MVM). * If enoxaparin reduces the occurrence or severity of MVM among patients with a prior adverse pregnancy outcome that occurred in the setting of MVM.

Research Team

Sunitha Suresh, MD

Principal Investigator

Endeavor Health

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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]

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]

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 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]

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]

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]

References

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

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

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

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

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

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

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

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

5. England 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. [2023]

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

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

7. Germany 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. [2021]

8. England 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. [2023]

9. United States 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. [2020]

10. Japan pubmed.ncbi.nlm.nih.gov

Selexipag for Chronic Thromboembolic Pulmonary Hypertension in Japanese Patients - A Double-Blind, Randomized, Placebo-Controlled, Multicenter Phase II Study. [2021]

11. England 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. [2022]

12. Switzerland pubmed.ncbi.nlm.nih.gov

A Canadian, retrospective, multicenter experience with selexipag for a heterogeneous group of pediatric pulmonary hypertension patients. [2023]