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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 : November 7, 2018
Sponsor:
Collaborator:
Cromsource
Information provided by (Responsible Party):
Miltenyi Biotec GmbH

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.

Condition or disease Intervention/treatment Phase
Preeclampsia Device: TheraSorb sFlt-1 adsorber Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 23 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : September 2016
Estimated Primary Completion Date : April 2019
Estimated Study Completion Date : January 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Phase 0 - healthy volunteers
Phase 0 is an initial safety phase where subjects will undergo one single TheraSorb sFlt-1 adsorber apheresis procedure.
Device: TheraSorb sFlt-1 adsorber
Removal of excessive sFlt-1 from the plasma of subjects/ patients with therapeutic apheresis.

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.
Device: TheraSorb sFlt-1 adsorber
Removal of excessive sFlt-1 from the plasma of subjects/ patients with therapeutic apheresis.

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.
Device: TheraSorb sFlt-1 adsorber
Removal of excessive sFlt-1 from the plasma of subjects/ patients with therapeutic apheresis.




Primary Outcome Measures :
  1. Occurrence of AEs and SAEs in healthy volunteers until the 2 weeks follow-up (Phase 0) [ Time Frame: until 2 weeks post treatment ]
  2. 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 ]

Secondary Outcome Measures :
  1. Phase 0: Determine changes of sFlt-1 levels. [ Time Frame: until 2 weeks post treatment ]
  2. 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) ]
  3. Phase 0: Concentration of antibody leaching during an apheresis procedure [ Time Frame: During an apheresis procedure (1 day) ]
  4. Phase 0: Change of HAMA levels in pre- and post apheresis blood [ Time Frame: until 2 weeks post treatment ]
  5. Phase 0: Evaluate blood pressure values [ Time Frame: until 2 weeks post treatment ]
  6. Phase 0: Evaluate spot urine values [ Time Frame: until 2 weeks post treatment ]
  7. Phase A/B: Occurrence of SAEs in the one year follow-up period [ Time Frame: until end of FU, (1 year) ]
  8. 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 ]
  9. Phases A and B: Evaluate maternal sFlt-1 levels. [ Time Frame: Constant measures throughout the trial until delivery (up to 19 weeks) ]
  10. Phases A/B: Evaluate the sFlt-1/PlGF ratio. [ Time Frame: Constant measures throughout the trial until delivery (up to 19 weeks) ]
  11. Phases A/B:Evaluate neonatal umbilical cord blood sFlt-1 levels at birth. [ Time Frame: at birth ]
  12. Phases A/B: Determine HAMA levels [ Time Frame: until 6 week FU visit ]
  13. Phases A/B: Time and method of delivery, and anesthesia administered [ Time Frame: at birth ]
  14. Phases A and B: Determine the post-partum maternal and neonatal length of hospitalization. [ Time Frame: Following birth up to one year ]
  15. Phases A/B: Evaluate standard markers of fetal development throughout pregnancy. [ Time Frame: From start of trial until delivery (up to 19 weeks) ]
  16. Phases A/B: Evaluate standard markers of neonatal development. [ Time Frame: Directly following delivery until end of FU (1 year) ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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/ renin-angiotensin-system blocker;
  • 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 infection;
  • 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
  • Various fetal exclusion criteria

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.

Information from the National Library of Medicine

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): NCT02923206


Contacts
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Contact: Thomas F Hiemstra, MD +44 (0) 1223 336 817 tfh24@cam.ac.uk

Locations
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United Kingdom
Cambridge Clinical Trials Unit, Addenbrooke's Hospital Recruiting
Cambridge, United Kingdom, CB2 0QQ
Contact: Thomas F Hiemstra, MD    +44 (0) 1223 336 817    tfh24@cam.ac.uk   
King's College Hospital NHS Foundation Trust Recruiting
London, United Kingdom, SE5 9RS
Contact: Kate Bramham, MD         
Imperial College Healthcare NHS Trust Not yet recruiting
London, United Kingdom, W12 0HS
Contact: Liz Lightstone, Prof         
Newcastle upon Tyne Hospitals NHS Foundation Trust Recruiting
Newcastle Upon Tyne, United Kingdom, NE7 7DN
Contact: Paul Ayuk, MD         
Oxford Radcliffe Hospitals Nhs, John Radcliffe Hospital Recruiting
Oxford, United Kingdom, OX3 9DU
Contact: Lucy Mackillop, MD         
Sponsors and Collaborators
Miltenyi Biotec GmbH
Cromsource
Investigators
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Principal Investigator: Thomas F Hiemstra, MD Cambridge Clinical Trials Unit Addenbrooke's Hospital

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Responsible Party: Miltenyi Biotec GmbH
ClinicalTrials.gov Identifier: NCT02923206     History of Changes
Other Study ID Numbers: M-2016-313
First Posted: October 4, 2016    Key Record Dates
Last Update Posted: November 7, 2018
Last Verified: November 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Miltenyi Biotec GmbH:
apheresis
pregnancy
pre-eclampsia
PE
sFlt-1
Pre-term

Additional relevant MeSH terms:
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Pre-Eclampsia
Hypertension, Pregnancy-Induced
Pregnancy Complications