The Use of Eculizumab in HELLP Syndrome
Condition: HELLP Syndrome (HELLP), Third Trimester; Complement Abnormality; Morbidity;Newborn; Maternal Injury; Preeclampsia Severe
MeSH terms: Pre-Eclampsia; HELLP Syndrome; Syndrome
Study type: Interventional
Phase: Phase 1

Summary: 
      This research study is being performed to see if women diagnosed with early preterm
      Hemolysis, Elevated Liver Enzymes, Low Platelets (HELLP) syndrome (estimated gestational ages
      of 23-30 weeks) benefit from a medication called eculizumab (ECU). This drug blocks a part of
      the immune system called complement. By blocking this part of the immune system, eculizumab
      may stop or reverse the progression of the HELLP syndrome disease. The investigators will
      also look to see if this drug is effective and benefits both the mother and fetus.
    

Detailed description: 
      Preeclampsia is a devastating multisystem disorder of pregnancy that manifests as
      hypertension with or without proteinuria and/or end organ damage caused by endothelial
      dysfunction and occurs in 3-5% of all pregnancies. Notably, preeclampsia accounts for 30% of
      all preterm deliveries, which results in neonatal intensive care unit admissions, increased
      health care cost, severe neonatal morbidity, and neonatal mortality. HELLP (hemolysis,
      elevated liver enzymes, and low platelets) syndrome is the most severe variant of this
      disorder, and affects approximately 0.1-0.2% of all pregnancies. Despite its prevalence, the
      cellular biology of HELLP syndrome is unclear resulting in supportive treatment regimens like
      fetal monitoring, steroids for fetal lung maturity, magnesium for seizure prophylaxis,
      management of hypertension and ultimately delivery that results in iatrogenic preterm birth.

      Complement is an enzymatic cascade of approximately 50 proteins which are activated by the
      classic pathway of complement, the lectin pathway of complement, and the alternative pathway
      of complement (APC). While the classic pathway depends on antigen-antibody complexes (i.e.,
      lupus) for activation, the APC is antibody independent and has various triggers including
      infection, trauma, and pregnancy.

      The investigators' research lab created a novel functional assay, the modified Ham (mHam)
      assay, to diagnose highly morbid diseases of the APC such atypical hemolytic uremic syndrome
      (aHUS). Because of the phenotypic similarities of aHUS and HELLP syndrome the investigators'
      lab undertook a study to test women diagnosed with complete (classic) HELLP and partial
      (atypical) HELLP syndrome established by Tennessee and American College of Obstetrics and
      Gynecology (ACOG) criteria to observe if there was dysregulation and overactivation of the
      APC. The investigators found that most women with HELLP syndrome have APC upregulation;
      furthermore, it could be inhibited in vitro with anti-C5 monoclonal antibody. In addition,
      the investigators recently showed approximately 50% of women with HELLP syndrome have
      germline mutations associated with regulatory proteins of the APC 12. These are the same
      mutations associated with aHUS; further, 4 of the 5 women with germline mutations are
      positive by the mHam assay correlating genotype to phenotype. With the investigators' current
      data that HELLP syndrome is similar to aHUS, the investigators propose an open label clinical
      trial of ECU administration to women with HELLP syndrome at 23-30 weeks gestation.
    

Intervention name(s): Eculizumab
Intervention type(s): Drug
Intervention description(s): Participants will receive eculizumab at diagnosis of HELLP syndrome. Participants will receive a maximum of 4 doses.
Other intervention name(s): Soliris
Intervention MeSH terms: Eculizumab
Intervention model: Single Group Assignment
Intervention model description: This will be an open label, phase 1 clinical trial. The investigators will investigate if eculizumab halts or prevents worsening or HELLP syndrome in women at 23-28 weeks gestation.
Masking: None (Open Label)
Primary purpose: Treatment