IMPACT Study: IMProve Pregnancy in APS With Certolizumab Therapy

Pregnancy Complications Clinical Trial

Official title: Certolizumab to Prevent Pregnancy Complications in High-Risk Patients With APS or SLE - (IMPACT Study: IMProve Pregnancy in APS With Certolizumab Therapy)

Status Recruiting

Clinical Trial Summary

This treatment trial evaluates the addition of an anti-tumor necrosis factor-alpha drug, certolizumab, to usual treatment (a heparin agent and low-dose aspirin) in pregnant women with antiphospholipid syndrome (APS) and repeatedly positive tests for lupus anticoagulant (LAC) to determine if this regimen will improve pregnancy outcomes. All enrolled patients will receive certolizumab, and pregnancy outcomes will be compared to those of women with APS and repeatedly positive tests for LAC enrolled in a previous study by the investigators.

Clinical Trial Description

Antiphospholipid syndrome (APS) is an autoimmune disorder that occurs most commonly in women of reproductive-age and is associated with thrombosis and adverse pregnancy outcomes (APOs), such as fetal loss and preterm birth due to severe preeclampsia (PE) or placental insufficiency (PI). Traditional therapy for APS during pregnancy has been a heparin agent and low dose aspirin. However, in PROMISSE, a prospective observational study of 724 patients, 44% of pregnancies in women with APS and LAC resulted in APOs despite treatment with heparin and low dose aspirin.

The APOs in women with APS and LAC are due to failure of adequate vascularization of the developing placenta and subsequent inadequate blood flow to the placenta and fetus. Mouse models of APS show that poor placental vascularization in APS is a result of inflammation in the placenta. This inflammation leads to recruitment of neutrophils and release of more inflammatory mediators and anti-angiogenic factors. In the mouse model tumor necrosis factor-alpha is a critical downstream effector of abnormal placental development and fetal damage, and tumor necrosis factor-alpha blockade during pregnancy restores angiogenic balance, normalizes placental vascularization, and rescues pregnancies.

Based on our observations in PROMISSE and the favorable results of tumor necrosis factor-alpha blockade in our mouse models, we hypothesize that tumor necrosis factor-alpha blockade will significantly decrease the rate of fetal death and preterm delivery due to PE and PI in women with APS and LAC. The study investigators aim to determine whether tumor necrosis factor-alpha blockade during pregnancy, added to a regimen of heparin and low dose aspirin, (1) reduces the rate of APOs in women with clinical APS and LAC, and (2) alters angiogenic markers of poor placental vascularization. Investigators will conduct an open label trial of certolizumab (a tumor necrosis factor-alpha inhibitor that does not cross the placenta). The regimen of heparin and low dose aspiring is a standard of care treatment for this patient population and is not considered part of the research intervention. ;

Related Conditions & MeSH terms

• Antiphospholipid Syndrome
• Antiphospholipid Syndrome in Pregnancy
• High Risk Pregnancy
• Lupus Anticoagulant Disorder
• Pregnancy Complications

• NCT number: NCT03152058
• Study type: Interventional
• Source: University of Utah
• Contact: Joseph Worden
• Phone: 801-585-7617
• Email: joseph.worden@hsc.utah.edu
• Status: Recruiting
• Phase: Phase 2
• Start date: May 17, 2017
• Completion date: December 2025