Removal of Anti-Angiogenic Proteins in Preeclampsia Before Delivery

NCT01404910 | Completed DMC

• 1 other identifier: 2012-P-000467/1
• Study Type: interventional
• Target: 11
• Locations: 2 countries
• Sites: 3

Brief Summary

Preeclampsia is a syndrome that occurs in approximately 3% to 8% of pregnancies and is associated with considerable maternal and neonatal morbidity and mortality. Except for termination of the pregnancy, effective treatments/preventative measures for preeclampsia are lacking. Although prolongation of pregnancy benefits the fetus, it is detrimental to the mother, and is associated with hypertension, proteinuria, and symptoms that suggest kidney, brain, liver and cardiovascular system involvement. Placental soluble fms-like tyrosine kinase 1 (sFlt-1) is elevated in women with preeclampsia, with levels that fall after delivery. sFlt-1 is a variant of the vascular endothelial growth factor (VEGF) receptor Flt-1, and in the circulation, acts as a potent VEGF and placental growth factor (PlGF) antagonist. Given that sFlt-1 levels are elevated in preeclampsia, we are investigating if removal of sFlt-1 from the plasma of women with preeclampsia can improve maternal and fetal outcomes. Short-term extracorporeal apheresis with the LIPOSORBER LA-15 System will be the primary intervention using methods that have been previously applied in pregnant women with familial hypercholesterolemia.

Conditions

Preeclampsia

Keywords

Pregnancy; Preeclampsia; Pre-term; sFlt-1; Apheresis; Hypertension; Proteinuria; VEGF

Outcome Measures

Primary Outcomes (1)

• sFlt-1 levels measured immediately prior to each apheresis treatment, and at 2-4, 12, 24, etc. (every 24 hours) following termination of apheresis to determine kinetics of sFlt-1 clearance (until delivery).

  The study period for each patient will be from initiation of the device until 30 days (± 7 days) after delivery. Additional assessments will be performed at 90 and 365 days (± 7 days, respectively) using maternal and neonatal medical records and/or by telephone contact with the mother.

  12 months

Secondary Outcomes (2)

• Maternal and fetal safety

  12 months

• Maternal and fetal efficacy

  12 months

Study Arms (1)

Apheresis

EXPERIMENTAL

Apheresis using Liposorber LA-15 System

Device: Apheresis using Liposorber LA-15 System

Interventions

Apheresis using Liposorber LA-15 System DEVICE

The Liposorber LA-15 Device is a dextran sulfate cellulose column, one of several currently approved in Europe and United States for pheresis of lipoproteins in the treatment of familial hypercholesterolemia. Such devices have been in use for over 30 years. Published experience in pregnant women with familial hypercholesterolemia suggests that lipoprotein pheresis can be safely used in pregnancy after appropriate individual benefit/risk assessment for both mother and fetus is considered. The Liposorber LA-15 system selected for this trial has been evaluated for its ability to efficiently and selectively remove sFlt-1 in vitro.

Apheresis

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Signed informed consent in a pregnant woman ages 18 and 45 years hospitalized for pre-term preeclampsia
• Pre-term preeclampsia defined by systolic BP ≥140 mm Hg or ≥90 mm Hg diastolic at or after 23 weeks of gestation or at or before 32 weeks in gestation in a woman with previously normal BP and proteinuria 0.3 grams in a 24-hour specimen or urine protein/creatinine ratio \>0.30.
• sFlt-1/PlGF ratio \>85 (blood levels of sFlt-1 and PlGF determined using CE-approved Roche Diagnostics assays).

You may not qualify if:

• Maternal:
• Taking any form of angiotensin cascade blocker
• History or diagnosis of pre-existing chronic hypertension (first 3 patients only)
• History of cardiac impairments including uncontrolled arrhythmia, unstable angina, decompensated congestive heart failure or valvular disease
• History or diagnosis of chronic renal disease
• Patients receiving anticoagulation therapy prior to study entry
• Anticipated immediate delivery within 24 hours
• Signs of central nervous system (CNS) dysfunction, including seizures, cerebral edema (CT-scan or MRI)
• History of thyroid disease
• History of liver abnormalities
• Pulmonary edema
• Thrombocytopenia (platelet count \< 100,000/mm3)
• Anemia - hemoglobin \< 8 g/dL
• Evidence of "reverse Doppler" flow on umbilical Doppler
• Placenta previa

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Kaneka Medical America LLC: collaborator

Study Sites (3)

Massachusetts General Hospital

Boston, Massachusetts, 02116, United States

Location

University Hospital of Cologne (Universitat zu Koln)

Cologne, 50923, Germany

Location

University Hospital Leipzig

Leipzig, Germany

Location

Related Publications (3)

• Thadhani R, Kisner T, Hagmann H, Bossung V, Noack S, Schaarschmidt W, Jank A, Kribs A, Cornely OA, Kreyssig C, Hemphill L, Rigby AC, Khedkar S, Lindner TH, Mallmann P, Stepan H, Karumanchi SA, Benzing T. Pilot study of extracorporeal removal of soluble fms-like tyrosine kinase 1 in preeclampsia. Circulation. 2011 Aug 23;124(8):940-50. doi: 10.1161/CIRCULATIONAHA.111.034793. Epub 2011 Aug 1.

  PMID: 21810665 BACKGROUND

• Easterling TR. Apheresis to Treat Preeclampsia: Insights, Opportunities and Challenges. J Am Soc Nephrol. 2016 Mar;27(3):663-5. doi: 10.1681/ASN.2015070794. Epub 2015 Sep 24. No abstract available.

  PMID: 26405110 BACKGROUND

• Thadhani R, Hagmann H, Schaarschmidt W, Roth B, Cingoez T, Karumanchi SA, Wenger J, Lucchesi KJ, Tamez H, Lindner T, Fridman A, Thome U, Kribs A, Danner M, Hamacher S, Mallmann P, Stepan H, Benzing T. Removal of Soluble Fms-Like Tyrosine Kinase-1 by Dextran Sulfate Apheresis in Preeclampsia. J Am Soc Nephrol. 2016 Mar;27(3):903-13. doi: 10.1681/ASN.2015020157. Epub 2015 Sep 24.

  PMID: 26405111 RESULT

MeSH Terms

Conditions

Pre-Eclampsia; Premature Birth; Hypertension; Proteinuria

Condition Hierarchy (Ancestors)

Hypertension, Pregnancy-Induced; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Obstetric Labor, Premature; Obstetric Labor Complications; Vascular Diseases; Cardiovascular Diseases; Urination Disorders; Urologic Diseases; Female Urogenital Diseases; Male Urogenital Diseases; Urological Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Ravi I Thadhani, MD, MPH

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

• Thomas Benzing, MD

  University of Koln

  PRINCIPAL INVESTIGATOR

• Holger Stepan, MD

  University of Leipzig

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Clinical Research in Nephrology

Study Record Dates

• First Submitted: July 26, 2011
• First Posted: July 28, 2011
• Study Start: May 1, 2013
• Primary Completion: September 1, 2015
• Study Completion: September 1, 2015
• Last Updated: March 16, 2017

Record last verified: 2017-03

Data Sharing

• IPD Sharing: Will not share

Locations

DE (2); US (1)