Clinical Trial: IMPACT Study: IMProve Pregnancy in APS With Certolizumab Therapy

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

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

Brief 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.

Detailed Summary:

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. In
Sponsor: Ware Branch

Current Primary Outcome: Fetal death and/or preterm delivery (<34 weeks) due to PE or PI in women with APS and LAC [ Time Frame: 8 weeks gestation through 6-weeks postpartum ]

Either of the following will constitute a primary outcome:

  1. Fetal death (>10 wks gestation)
  2. Severe preeclampsia or placental insufficiency requiring delivery prior to 34 weeks gestation.


Original Primary Outcome: Same as current

Current Secondary Outcome: Additional adverse outcomes or pertinent concerns, possibly related to study intervention [ Time Frame: 8 weeks gestation through 6-weeks postpartum ]

Any one of the following is considered a secondary outcome:

  1. Neonatal death due to complications of prematurity because of preterm delivery for PE or PI
  2. Preterm labor or preterm rupture of membranes resulting in delivery prior to 36 weeks gestation
  3. PE or PI not requiring delivery prior to 34 weeks gestation
  4. Gestational age at delivery
  5. Maternal thrombosis
  6. Small-for-gestational age birthweight (<10th percentile)
  7. Known adverse reactions to certolizumab.


Original Secondary Outcome: Same as current

Information By: University of Utah

Dates:
Date Received: May 1, 2017
Date Started: May 17, 2017
Date Completion: May 2021
Last Updated: May 17, 2017
Last Verified: May 2017