search
Back to results

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

Primary Purpose

Preeclampsia

Status
Recruiting
Phase
Not Applicable
Locations
International
Study Type
Interventional
Intervention
TheraSorb sFlt-1 adsorber
Sponsored by
Miltenyi Biomedicine GmbH
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Preeclampsia focused on measuring apheresis, pregnancy, pre-eclampsia, PE, sFlt-1, Pre-term

Eligibility Criteria

18 Years - 45 Years (Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

  • Universitätsklinikum KölnRecruiting
  • Universitätsklinikum LeipzigRecruiting
  • Cambridge Clinical Trials Unit, Addenbrooke's Hospital
  • Oxford University Hospitals NHS Foundation Trust, John Radcliffe HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Phase 0 - healthy volunteers

Phase A - preeclampsia patients

Phase B - preeclampsia patients

Arm Description

Phase 0 is an initial safety phase where subjects will undergo one single TheraSorb sFlt-1 adsorber apheresis procedure.

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.

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.

Outcomes

Primary Outcome Measures

Occurrence of AEs and SAEs in healthy volunteers until the 2 weeks follow-up (Phase 0)
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).

Secondary Outcome Measures

Phase 0: Determine changes of sFlt-1 levels.
Phase 0: Complement activation levels pre-, during and post apheresis.
Phase 0: Concentration of antibody leaching during an apheresis procedure
Phase 0: Change of HAMA levels in pre- and post apheresis blood
Phase 0: Evaluate blood pressure values
Phase 0: Evaluate spot urine values
Phase A/B: Occurrence of SAEs in the one year follow-up period
Phases A/B: Evaluate antibody leaching in phase A.
Phases A and B: Evaluate maternal sFlt-1 levels.
Phases A/B: Evaluate the sFlt-1/PlGF ratio.
Phases A/B:Evaluate neonatal umbilical cord blood sFlt-1 levels at birth.
Phases A/B: Determine HAMA levels
Phases A/B: Time and method of delivery, and anesthesia administered
Phases A and B: Determine the post-partum maternal and neonatal length of hospitalization.
Phases A/B: Evaluate standard markers of fetal development throughout pregnancy.
Phases A/B: Evaluate standard markers of neonatal development.

Full Information

First Posted
September 19, 2016
Last Updated
August 11, 2022
Sponsor
Miltenyi Biomedicine GmbH
Collaborators
Cromsource
search

1. Study Identification

Unique Protocol Identification Number
NCT02923206
Brief Title
Proof-of-Concept Trial on Selective Removal of sFlt-1 in Pregnant Women With Preeclampsia Via Apheresis
Acronym
SAVE
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
Study Type
Interventional

2. Study Status

Record Verification Date
August 2022
Overall Recruitment Status
Recruiting
Study Start Date
September 2016 (Actual)
Primary Completion Date
December 2023 (Anticipated)
Study Completion Date
December 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Miltenyi Biomedicine GmbH
Collaborators
Cromsource

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Preeclampsia
Keywords
apheresis, pregnancy, pre-eclampsia, PE, sFlt-1, Pre-term

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
23 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Phase 0 - healthy volunteers
Arm Type
Experimental
Arm Description
Phase 0 is an initial safety phase where subjects will undergo one single TheraSorb sFlt-1 adsorber apheresis procedure.
Arm Title
Phase A - preeclampsia patients
Arm Type
Experimental
Arm Description
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.
Arm Title
Phase B - preeclampsia patients
Arm Type
Experimental
Arm Description
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 Type
Device
Intervention Name(s)
TheraSorb sFlt-1 adsorber
Intervention Description
Removal of excessive sFlt-1 from the plasma of subjects/ patients with therapeutic apheresis.
Primary Outcome Measure Information:
Title
Occurrence of AEs and SAEs in healthy volunteers until the 2 weeks follow-up (Phase 0)
Time Frame
until 2 weeks post treatment
Title
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 Measure Information:
Title
Phase 0: Determine changes of sFlt-1 levels.
Time Frame
until 2 weeks post treatment
Title
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)
Title
Phase 0: Concentration of antibody leaching during an apheresis procedure
Time Frame
During an apheresis procedure (1 day)
Title
Phase 0: Change of HAMA levels in pre- and post apheresis blood
Time Frame
until 2 weeks post treatment
Title
Phase 0: Evaluate blood pressure values
Time Frame
until 2 weeks post treatment
Title
Phase 0: Evaluate spot urine values
Time Frame
until 2 weeks post treatment
Title
Phase A/B: Occurrence of SAEs in the one year follow-up period
Time Frame
until end of FU, (1 year)
Title
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
Title
Phases A and B: Evaluate maternal sFlt-1 levels.
Time Frame
Constant measures throughout the trial until delivery (up to 19 weeks)
Title
Phases A/B: Evaluate the sFlt-1/PlGF ratio.
Time Frame
Constant measures throughout the trial until delivery (up to 19 weeks)
Title
Phases A/B:Evaluate neonatal umbilical cord blood sFlt-1 levels at birth.
Time Frame
at birth
Title
Phases A/B: Determine HAMA levels
Time Frame
until 6 week FU visit
Title
Phases A/B: Time and method of delivery, and anesthesia administered
Time Frame
at birth
Title
Phases A and B: Determine the post-partum maternal and neonatal length of hospitalization.
Time Frame
Following birth up to one year
Title
Phases A/B: Evaluate standard markers of fetal development throughout pregnancy.
Time Frame
From start of trial until delivery (up to 19 weeks)
Title
Phases A/B: Evaluate standard markers of neonatal development.
Time Frame
Directly following delivery until end of FU (1 year)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility 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; 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jörg Liebmann, PhD
Email
joergli@miltenyi.com
Facility Information:
Facility Name
Universitätsklinikum Köln
City
Cologne
ZIP/Postal Code
50937
Country
Germany
Individual Site Status
Recruiting
Facility Name
Universitätsklinikum Leipzig
City
Leipzig
ZIP/Postal Code
04103
Country
Germany
Individual Site Status
Recruiting
Facility Name
Cambridge Clinical Trials Unit, Addenbrooke's Hospital
City
Cambridge
ZIP/Postal Code
CB2 0QQ
Country
United Kingdom
Individual Site Status
Not yet recruiting
Facility Name
Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital
City
Oxford
ZIP/Postal Code
OX3 9DU
Country
United Kingdom
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

We'll reach out to this number within 24 hrs