The Use of Eculizumab in HELLP Syndrome
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|ClinicalTrials.gov Identifier: NCT04103489|
Recruitment Status : Not yet recruiting
First Posted : September 25, 2019
Last Update Posted : October 11, 2019
|Condition or disease||Intervention/treatment||Phase|
|HELLP Syndrome (HELLP), Third Trimester Complement Abnormality Morbidity;Newborn Maternal Injury Preeclampsia Severe||Drug: Eculizumab||Phase 1|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||15 participants|
|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)|
|Official Title:||Eculizumab in HELLP Syndrome|
|Estimated Study Start Date :||January 1, 2020|
|Estimated Primary Completion Date :||December 31, 2022|
|Estimated Study Completion Date :||January 4, 2023|
Experimental: HELLP Syndrome at less than 28 weeks gestation
Women diagnosed with HELLP syndrome at 23-30 weeks gestation will receive eculizumab.
Participants will receive eculizumab at diagnosis of HELLP syndrome. Participants will receive a maximum of 4 doses.
Other Name: Soliris
- Change in aspartate aminotransferase (AST) level [ Time Frame: Baseline, 72 hours ]AST measured in units/L.
- Change in alanine aminotransferase (ALT) [ Time Frame: Baseline, 72 hours ]ALT measured in IU/L.
- Change in lactate dehydrogenase levels (LDH) [ Time Frame: Baseline, 72 hours ]LDH measured in units/L.
- Latency of pregnancy [ Time Frame: Up to 7 days ]Latency of pregnancy measured in days after eculizumab administration
- Maternal number of units of blood products transfused [ Time Frame: Up to 7 days ]Blood products (packed red blood cells, fresh frozen plasma, platelets, cryoprecipitate) measured in units.
- Maternal postpartum length of stay [ Time Frame: Up to 36 days ]Postpartum length of stay, measured from delivery to time of discharge in days.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04103489
|Contact: Arthur J Vaughtemail@example.com|
|Principal Investigator:||Arthur J Vaught||Johns Hopkins University|