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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
Sponsor:
Information provided by (Responsible Party):
Johns Hopkins University

Tracking Information
First Submitted Date  ICMJE September 24, 2019
First Posted Date  ICMJE September 25, 2019
Last Update Posted Date October 11, 2019
Estimated Study Start Date  ICMJE January 1, 2020
Estimated Primary Completion Date December 31, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 24, 2019)
  • 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.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT04103489 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 24, 2019)
  • 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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE The Use of Eculizumab in HELLP Syndrome
Official Title  ICMJE Eculizumab in HELLP Syndrome
Brief 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE 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
Condition  ICMJE
  • HELLP Syndrome (HELLP), Third Trimester
  • Complement Abnormality
  • Morbidity;Newborn
  • Maternal Injury
  • Preeclampsia Severe
Intervention  ICMJE Drug: Eculizumab
Participants will receive eculizumab at diagnosis of HELLP syndrome. Participants will receive a maximum of 4 doses.
Other Name: Soliris
Study Arms  ICMJE Experimental: HELLP Syndrome at less than 28 weeks gestation
Women diagnosed with HELLP syndrome at 23-30 weeks gestation will receive eculizumab.
Intervention: Drug: Eculizumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: September 24, 2019)
15
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 4, 2023
Estimated Primary Completion Date December 31, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years to 50 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Arthur J Vaught 4048496018 avaught2@jhmi.edu
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04103489
Other Study ID Numbers  ICMJE IRB00193549
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Johns Hopkins University
Study Sponsor  ICMJE Johns Hopkins University
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Arthur J Vaught Johns Hopkins University
PRS Account Johns Hopkins University
Verification Date October 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP