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

Preeclampsia Clinical Trial

— 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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02923206
• Other study ID #: M-2016-313
• Status: Recruiting
• Phase: N/A
• Start date: September 2016
• Est. completion date: December 2024

Study information

• Verified date: August 2022
• Source: Miltenyi Biomedicine GmbH
• Contact: Jörg Liebmann, PhD
• Email: joergli[@]miltenyi.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 23
• Est. completion date: December 2024
• Est. primary completion date: December 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 45 Years

Eligibility

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.

Related Conditions & MeSH terms

• Pre-Eclampsia
• Preeclampsia

Intervention

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

Locations

Country	Name	City	State
Germany	Universitätsklinikum Köln	Cologne
Germany	Universitätsklinikum Leipzig	Leipzig
United Kingdom	Cambridge Clinical Trials Unit, Addenbrooke's Hospital	Cambridge
United Kingdom	Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital	Oxford

Sponsors (2)

Lead Sponsor	Collaborator
Miltenyi Biomedicine GmbH	Cromsource

Countries where clinical trial is conducted

Germany,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Occurrence of AEs and SAEs in healthy volunteers until the 2 weeks follow-up (Phase 0)		until 2 weeks post treatment
Primary	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).		until 6 weeks post delivery
Secondary	Phase 0: Determine changes of sFlt-1 levels.		until 2 weeks post treatment
Secondary	Phase 0: Complement activation levels pre-, during and post apheresis.		Before, during and directly following the performance of the single apheresis treatment (1 day)
Secondary	Phase 0: Concentration of antibody leaching during an apheresis procedure		During an apheresis procedure (1 day)
Secondary	Phase 0: Change of HAMA levels in pre- and post apheresis blood		until 2 weeks post treatment
Secondary	Phase 0: Evaluate blood pressure values		until 2 weeks post treatment
Secondary	Phase 0: Evaluate spot urine values		until 2 weeks post treatment
Secondary	Phase A/B: Occurrence of SAEs in the one year follow-up period		until end of FU, (1 year)
Secondary	Phases A/B: Evaluate antibody leaching in phase A.		During the performance of the single apheresis treatment in Phase A (1 day) as well as pre and 3hrs post apheresis
Secondary	Phases A and B: Evaluate maternal sFlt-1 levels.		Constant measures throughout the trial until delivery (up to 19 weeks)
Secondary	Phases A/B: Evaluate the sFlt-1/PlGF ratio.		Constant measures throughout the trial until delivery (up to 19 weeks)
Secondary	Phases A/B:Evaluate neonatal umbilical cord blood sFlt-1 levels at birth.		at birth
Secondary	Phases A/B: Determine HAMA levels		until 6 week FU visit
Secondary	Phases A/B: Time and method of delivery, and anesthesia administered		at birth
Secondary	Phases A and B: Determine the post-partum maternal and neonatal length of hospitalization.		Following birth up to one year
Secondary	Phases A/B: Evaluate standard markers of fetal development throughout pregnancy.		From start of trial until delivery (up to 19 weeks)
Secondary	Phases A/B: Evaluate standard markers of neonatal development.		Directly following delivery until end of FU (1 year)