The Use of Eculizumab in HELLP Syndrome
关键词
抽象
描述
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.
日期
最后验证: | 06/30/2020 |
首次提交: | 09/23/2019 |
提交的预估入学人数: | 09/23/2019 |
首次发布: | 09/24/2019 |
上次提交的更新: | 07/13/2020 |
最近更新发布: | 07/15/2020 |
实际学习开始日期: | 08/31/2020 |
预计主要完成日期: | 12/30/2022 |
预计完成日期: | 01/03/2023 |
状况或疾病
干预/治疗
Drug: HELLP Syndrome at less than 28 weeks gestation
相
手臂组
臂 | 干预/治疗 |
---|---|
Experimental: HELLP Syndrome at less than 28 weeks gestation Women diagnosed with HELLP syndrome at 23-30 weeks gestation will receive eculizumab. | Drug: HELLP Syndrome at less than 28 weeks gestation Participants will receive eculizumab at diagnosis of HELLP syndrome. Participants will receive a maximum of 4 doses. |
资格标准
有资格学习的年龄 | 18 Years 至 18 Years |
有资格学习的性别 | Female |
接受健康志愿者 | 是 |
标准 | Inclusion Criteria: - Pregnant women diagnosed with HELLP syndrome less than 28 weeks gestation. Exclusion Criteria: Women with - Disseminated intravascular coagulopathy - Non-reassuring fetal status necessitating delivery - Non-viable fetuses - Stroke - Fetal demise intra-utero - Eclamptic seizure - Known atypical hemolytic uremic syndrome - Familial or acquired thrombocytopenia purpura - Paroxysmal nocturnal hemoglobinuria - Allergy to eculizumab will be excluded. |
结果
主要结果指标
1. Change in aspartate aminotransferase (AST) level [Baseline, 72 hours]
2. Change in alanine aminotransferase (ALT) [Baseline, 72 hours]
3. Change in lactate dehydrogenase levels (LDH) [Baseline, 72 hours]
次要成果指标
1. Latency of pregnancy [Up to 7 days]
2. Maternal number of units of blood products transfused [Up to 7 days]
3. Maternal postpartum length of stay [Up to 36 days]