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Proof-of-Concept Trial on Selective Removal of sFlt-1 in Pregnant Women With Preeclampsia Via Apheresis (SAVE)

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ClinicalTrials.gov Identifier: NCT02923206
Recruitment Status : Recruiting
First Posted : October 4, 2016
Last Update Posted : January 18, 2020
Sponsor:
Collaborator:
Cromsource
Information provided by (Responsible Party):
Miltenyi Biotec B.V. & Co. KG

Tracking Information
First Submitted Date  ICMJE September 19, 2016
First Posted Date  ICMJE October 4, 2016
Last Update Posted Date January 18, 2020
Actual Study Start Date  ICMJE September 2016
Estimated Primary Completion Date February 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 3, 2016)
  • Occurrence of AEs and SAEs in healthy volunteers until the 2 weeks follow-up (Phase 0) [ Time Frame: until 2 weeks post treatment ]
  • Occurrence of AEs and SAEs in pregnant subjects and the fetus or infant until the 6 weeks post-delivery visit is reached (Phase A-B). [ Time Frame: until 6 weeks post delivery ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 23, 2017)
  • Phase 0: Determine changes of sFlt-1 levels. [ Time Frame: until 2 weeks post treatment ]
  • Phase 0: Complement activation levels pre-, during and post apheresis. [ Time Frame: Before, during and directly following the performance of the single apheresis treatment (1 day) ]
  • Phase 0: Concentration of antibody leaching during an apheresis procedure [ Time Frame: During an apheresis procedure (1 day) ]
  • Phase 0: Change of HAMA levels in pre- and post apheresis blood [ Time Frame: until 2 weeks post treatment ]
  • Phase 0: Evaluate blood pressure values [ Time Frame: until 2 weeks post treatment ]
  • Phase 0: Evaluate spot urine values [ Time Frame: until 2 weeks post treatment ]
  • Phase A/B: Occurrence of SAEs in the one year follow-up period [ Time Frame: until end of FU, (1 year) ]
  • Phases A/B: Evaluate antibody leaching in phase A. [ Time Frame: During the performance of the single apheresis treatment in Phase A (1 day) as well as pre and 3hrs post apheresis ]
  • Phases A and B: Evaluate maternal sFlt-1 levels. [ Time Frame: Constant measures throughout the trial until delivery (up to 19 weeks) ]
  • Phases A/B: Evaluate the sFlt-1/PlGF ratio. [ Time Frame: Constant measures throughout the trial until delivery (up to 19 weeks) ]
  • Phases A/B:Evaluate neonatal umbilical cord blood sFlt-1 levels at birth. [ Time Frame: at birth ]
  • Phases A/B: Determine HAMA levels [ Time Frame: until 6 week FU visit ]
  • Phases A/B: Time and method of delivery, and anesthesia administered [ Time Frame: at birth ]
  • Phases A and B: Determine the post-partum maternal and neonatal length of hospitalization. [ Time Frame: Following birth up to one year ]
  • Phases A/B: Evaluate standard markers of fetal development throughout pregnancy. [ Time Frame: From start of trial until delivery (up to 19 weeks) ]
  • Phases A/B: Evaluate standard markers of neonatal development. [ Time Frame: Directly following delivery until end of FU (1 year) ]
Original Secondary Outcome Measures  ICMJE
 (submitted: October 3, 2016)
  • Phase 0: Determine changes of sFlt-1 levels. [ Time Frame: until 2 weeks post treatment ]
  • Phase 0: Complement activation levels pre-, during and post apheresis. [ Time Frame: Before, during and directly following the performance of the single apheresis treatment (1 day) ]
  • Phase 0: Concentration of antibody leaching during an apheresis procedure [ Time Frame: During an apheresis procedure (1 day) ]
  • Phase 0: Change of HAMA levels in pre- and post apheresis blood [ Time Frame: until 2 weeks post treatment ]
  • Phase 0: Evaluate blood pressure values [ Time Frame: until 2 weeks post treatment ]
  • Phase 0: Evaluate spot urine values [ Time Frame: until 2 weeks post treatment ]
  • Phase A/B: Occurrence of SAEs in the one year follow-up period [ Time Frame: until end of FU, (1 year) ]
  • Phases A/B: Evaluate antibody leaching in phase A. [ Time Frame: During the performance of the single apheresis treatment in Phase A (1 day) ]
  • Phases A and B: Evaluate maternal sFlt-1 levels. [ Time Frame: Constant measures throughout the trial until delivery (up to 19 weeks) ]
  • Phases A/B: Evaluate the sFlt-1/PlGF ratio. [ Time Frame: Constant measures throughout the trial until delivery (up to 19 weeks) ]
  • Phases A/B:Evaluate neonatal umbilical cord blood sFlt-1 levels at birth. [ Time Frame: at birth ]
  • Phases A/B: Determine HAMA levels [ Time Frame: until 6 week FU visit ]
  • Phases A/B: Time and method of delivery, and anesthesia administered [ Time Frame: at birth ]
  • Phases A and B: Determine the post-partum maternal and neonatal length of hospitalization. [ Time Frame: Following birth up to one year ]
  • Phases A/B: Evaluate standard markers of fetal development throughout pregnancy. [ Time Frame: From start of trial until delivery (up to 19 weeks) ]
  • Phases A/B: Evaluate standard markers of neonatal development. [ Time Frame: Directly following delivery until end of FU (1 year) ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Proof-of-Concept Trial on Selective Removal of sFlt-1 in Pregnant Women With Preeclampsia Via Apheresis
Official Title  ICMJE Proof-of-Concept Trial on Selective Removal of the Antiangiogenic Factor Soluble Fms-like Tyrosine Kinase-1 (sFlt-1) in Pregnant Women With Preeclampsia Via Apheresis Utilizing the Flt-1 Adsorption Column
Brief Summary This clinical investigation is a medical device trial to examine the safety and efficacy of TheraSorb sFlt-1 adsorber treatment of pregnant patients with preeclampsia.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Preeclampsia
Intervention  ICMJE Device: TheraSorb sFlt-1 adsorber
Removal of excessive sFlt-1 from the plasma of subjects/ patients with therapeutic apheresis.
Study Arms  ICMJE
  • Experimental: Phase 0 - healthy volunteers
    Phase 0 is an initial safety phase where subjects will undergo one single TheraSorb sFlt-1 adsorber apheresis procedure.
    Intervention: Device: TheraSorb sFlt-1 adsorber
  • Experimental: Phase A - preeclampsia patients
    Phase A is a safety and dose-finding phase during which pregnant women diagnosed with preeclampsia will undergo one single TheraSorb sFlt-1 adsorber apheresis procedure.
    Intervention: Device: TheraSorb sFlt-1 adsorber
  • Experimental: Phase B - preeclampsia patients
    Phase B is a safety and efficacy phase during which pregnant women diagnosed with preeclampsia will undergo TheraSorb sFlt-1 adsorber apheresis procedures up to twice weekly.
    Intervention: Device: TheraSorb sFlt-1 adsorber
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 Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 3, 2016)
23
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 2022
Estimated Primary Completion Date February 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Reduced criteria!

Phase 0

Inclusion Criteria:

  • Age ≥18 and ≤45 years;
  • Male or female;
  • Female subjects of childbearing potential must have a negative serum pregnancy test result at screening and practice two reliable methods of contraception throughout the study.

Exclusion Criteria:

  • Dysfunction of cerebral nervous system and/or heart disease;
  • History of preexisting chronic renal disease;
  • Treatment with ACE inhibitors;
  • Therapeutic full anticoagulation therapy prior to trial entry;
  • Liver abnormalities;
  • Clinically significant pulmonary edema and/or thrombocytopenia and/or anemia;
  • Active hepatitis B, C, or tuberculosis infection or HIV infection
  • Hypersensitivity to heparin and/or citrate;
  • Indications that prohibit transient anticoagulation using heparin and/or ACD-A-solutions;
  • Known intolerance to extracorporeal procedures in general or towards one of the individual excipients or towards other supporting agents;
  • Drug or alcohol abuse within the last 2 years;
  • Lack of compliance of subject;
  • History or diagnosis of severe periodontitis;

Phase A and B

Inclusion Criteria:

  • Age >18 and ≤45 years ;
  • Pregnant woman with pre-term preeclampsia
  • sFlt-1/PlGF ratio ≥85 ;
  • sFlt-1 level of ≥ 8000pg/mL

Exclusion Criteria:

Maternal exclusion criteria

  • History of cardiac impairments including uncontrolled arrhythmia, unstable angina, decompensated congestive heart failure or valve disease;
  • History of preexisting chronic renal disease (CKD stage >3a, eGFR ≤45ml/min/1.73m²);
  • Treatment with ACE inhibitors;
  • Therapeutic full anticoagulation therapy prior to trial entry;
  • Signs or history of clinically significant cerebral nervous system dysfunction;
  • History of clinically significant liver abnormalities;
  • Clinically significant pulmonary edema and/or thrombocytopenia and/or anemia;
  • Active hepatitis B, C, tuberculosis infection or HIV-positive status;
  • Any condition that the investigator deems a risk to the patient or fetus in completing the trial;
  • Indications that prohibit transient anticoagulation using heparin and/or ACD-A-solutions;
  • Drug or alcohol abuse within the last 2 years;
  • Lack of compliance of patient;
  • Known intolerance to extracorporeal procedures in general or to one of the excipients or other supporting agents;
  • Hypersensitivity to heparin and/or citrate;
  • < 30 0/7 weeks of gestation and abnormal CTG and/or abnormal Ductus venosus Doppler flow,
  • ≥30 0/7 weeks of gestation and Doppler evidence of umbilical artery Absent or Reversed End-Diastolic Velocity (AREDV);
  • Various Placental exclusion criteria;
  • Multiple pregnancy
  • History or diagnosis of severe periodontitis

Fetal exclusion criteria

  • Any known trisomy;
  • Amniotic fluid index <5cm (greatest single pocket <2cm);
  • Estimated fetal weight <3rd percentile for gestational age;
  • Fetus which are at high risk of heart disease;
  • Fetus with congenital heart defect;
  • Fetal signs of bleeding;
  • Hydrops fetalis;
  • Pathological fetal Doppler flow of the ductus venosus (absent A-wave in two measurements);
  • Evidence of severe fetal malformations;
  • Known infection of fetus;
  • Known severe anemia.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 45 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Contact: Thomas F Hiemstra, MD +44 (0) 1223 336 817 tfh24@cam.ac.uk
Listed Location Countries  ICMJE United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02923206
Other Study ID Numbers  ICMJE M-2016-313
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Miltenyi Biotec B.V. & Co. KG
Study Sponsor  ICMJE Miltenyi Biotec B.V. & Co. KG
Collaborators  ICMJE Cromsource
Investigators  ICMJE
Principal Investigator: Thomas F Hiemstra, MD Cambridge Clinical Trials Unit Addenbrooke's Hospital
PRS Account Miltenyi Biotec B.V. & Co. KG
Verification Date January 2020

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