Proof of Concept Study of IMMUNOadsorption Therapy in Patients With Idiopathic Pulmonary Arterial Hypertension

A Clinical Proof of Concept Study of IMMUNOadsorption Therapy in Patients With Idiopathic Pulmonary Arterial Hypertension

This clinical investigation is a medical device trial to examine the safety and efficacy of TheraSorb® Ig flex adsorber treatment (as an add-on to conventional treatment) used exclusively with the LIFE 18® apheresis system for extracorporeal application for IA therapy (5 treatments) performed over 5 to 8 consecutive days in patients with Idiopathic Pulmonary Arterial Hypertension and WHO functional classification III.

Study Overview

• Status: Completed
• Conditions: Idiopathic Pulmonary Arterial Hypertension
• Intervention / Treatment: Device: TheraSorb® - Ig flex

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 13353
    • Deutsches Herzzentrum Berlin, Klinik für Herz-, Thorax- und Gefäßchirurgie
  • Baden-Wuerttemberg
    • Heidelberg, Baden-Wuerttemberg, Germany, 69126/ 69120
      • Thoraxklinik am Universitätsklinikum Heidelberg in cooperation with Nierenzentrum Heidelberg
  • Mecklenburg-Western Pomerania
    • Greifswald, Mecklenburg-Western Pomerania, Germany, 17475
      • Universitätsmedizin Greifswald, Zentrum für Innere Medizin, Klinik und Poliklinik für Innere Medizin B
  • North-Rhine Westphalia
    • Cologne, North-Rhine Westphalia, Germany, 50937
      • Herzzentrum der Universität zu Köln, Klinik III für Innere Medizin und Zentrum für Molekulare Medizin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Able to understand and willing to sign the Informed Consent Form
• age > 18 and < 80 years at time of informed consent
• Idiopathic pulmonary arterial hypertension diagnosed by right heart catheter
• WHO functional classification III
• Application of conventional IPAH therapy, which has been stable for the prior 8 weeks
• Able to perform a 6-minute-walk test (MWT)
• Negative pregnancy test (β-HCG) at the start of the trial and appropriate contraception throughout the trial for women with child-bearing potential.

Exclusion Criteria:

• Pregnancy and/or lactation
• PAH of any cause other than permitted in the inclusion criteria, e.g. concomitantly to portal hypertension, complex congenital heart disease, reversed shunt, HIV infection, suspected pulmonary veno-occlusive disease
• Contraindication for right heart catheterization
• Any change in disease-targeted therapy within 8 weeks prior to inclusion
• Walking impairment due to causes other than IPAH that would preclude performance of a 6MWT
• Any patient who has received any investigational medication within 8 weeks prior to the start of this trial or who is scheduled to receive another investigational drug during the course of the trial between visits V1 and V9
• Known intolerance to immunoadsorption in general or to one of the excipients (e.g. sheep antibodies or agarose) or other supporting agents
• Hemoglobin concentration of < 75% below the lower limit of normal
• Systolic blood pressure < 85 mmHg
• Lack of compliance or other similar reason that, in the judgment of the Investigator, precludes satisfactory participation in the trial
• Concurrent severe or uncontrolled medical disease (i.e. uncontrolled diabetes, congestive heart failure, myocardial infarction within 6 months prior to the study, unstable and uncontrolled hypertension, chronic renal disease, or active uncontrolled generalized viral, bacterial and/ or mycotic infection) which by assessment of the treating Investigator could compromise patients safety or participation in the study
• Drug or alcohol abuse within the last 5 years
• Hypercoagulability
• Known severe immunodeficiency (e.g. AIDS)
• Severe lung disease: FEV1/FVC < 50%, total capacity < 60% of normal value
• Indications that prohibit transient anticoagulation using Heparin and/or ACD-A-solutions

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Immunoadsorption; Patients are treated with the TheraSorb® Ig flex adsorber used exclusively with the LIFE 18® apheresis system for extracorporeal application for IA therapy (5 treatments) performed over 5 to 8 consecutive days	Device: TheraSorb® - Ig flex; TheraSorb® Treatment with one TheraSorb® Ig flex adsorber pair, used exclusively with the LIFE 18® apheresis system for extracorporeal application for IA therapy. 5 treatments performed over 5 to 8 consecutive days.; Other Names: Immunoadsorption

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Primary endpoint is the change of pulmonary vascular resistance (PVR) at rest before immunoadsorption compared to 3 months after immunoadsorption therapy determined by right heart catheterization (RHC).	Baseline, 3 months after therapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
all-cause mortality	The patients will be followed for the duration of the study participation, an expected average of 6 months.	~6months
occurrence and number of Adverse Events	The patients will be followed for the duration of the study participation, an expected average of 6 months.	~6 months
Six-minute walk test (6MWT)		Measurements at baseline, ~1 week, ~1 month, ~3 months and ~6 months after start of therapy
Quality of life questionnaires	SF-36 EQ-5D™	Measurements at baseline, and after ~1 month, ~3 months, ~6 months
WHO functional classification	WHO functional classification of pulmonary hypertension (according to the Evian Symposium,1998, modified New York Heart Association (NYHA) Classification	Measurements at baseline, ~1 week, ~1 month, ~3 months and ~6 months after start of therapy
Analysis of Hemodynamics by right heart catheterization: RAP, PAPm, CO, CI, SvO2; sPAP	(Right atrial pressure, mean pulmonary arterial pressure, pulmonary capillary wedge pressure, cardiac output, cardiac index, venous oxygen saturation, systolic pulmonary arterial pressure.)	Measurements at baseline, after ~3 months
Reduction of IgG		Measurements at baseline, during each treatment visit, ~1 week, ~1 month and ~3 months after start of treatment

Collaborators and Investigators

• Sponsor: Miltenyi Biotec B.V. & Co. KG
• Investigators: Principal Investigator: Ekkehard Grünig, Prof. Dr., Heidelberg University

Study record dates

Study Major Dates

• Study Start: June 1, 2012
• Primary Completion (Actual): August 1, 2013
• Study Completion (Actual): November 1, 2013

Study Registration Dates

• First Submitted: May 29, 2012
• First Submitted That Met QC Criteria: June 6, 2012
• First Posted (Estimate): June 7, 2012

Study Record Updates

• Last Update Posted (Actual): July 10, 2020
• Last Update Submitted That Met QC Criteria: July 8, 2020
• Last Verified: December 1, 2013

More Information

Terms related to this study

• Keywords: Pulmonary Hypertension; Pulmonary Arterial Hypertension; immunoadsorption; TheraSorb
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension, Pulmonary; Hypertension; Pulmonary Arterial Hypertension; Familial Primary Pulmonary Hypertension
• Other Study ID Numbers: M-2010-224; CIV-11-10-002861 (Other Identifier: European Databank on Medical Devices - EUDAMED)