Immunoadsorption in Patients With Pulmonary Hypertension

Study Overview
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Brief Summary
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The purpose of this study is to investigate, if Immunoadsorption of autoantibodies with subsequent substitution of immunoglobulins is able to improve haemodynamics in patients with pulmonary hypertension.

Detailed Description
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Increased pulmonary precapillary vascular resistance due to vasoconstriction and vasoproliferative processes is the basic pathophysiological mechanism in the development of pulmonary hypertension (PH). In patients with pulmonary arterial hypertension (PH) production of endothelin-1 (ET-1) is increased and elevated ET-1 plasma levels correlate with PH severity As recently shown Autoantibodies against the Endothelin-1 Typ A and Angiotensin II Typ-1 Receptor, which have a high Incidence in PH-Patients, may also play an important role in the pathophysiology of PH (Dandel et al.). The concept of this study is that the elimination of these autoantibodies by Immunoadsorption with protein A may improve haemodynamics and patient wellbeing. Immunoglobulins are substituted after Immunoadsorption to minimize infection risk.

Official Title
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Randomized, Prospective Investigation on the Effects of Immunoadsorption on Pulmonary Vascular Resistance in Patients With Pulmonary Hypertension

Conditions
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Pulmonary Hypertension, Pulmonary Resistance

Intervention / Treatment
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* Procedure: immunoadsorption / immunglobulin substitution


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: pulmonary hypertension (PH) NYHA II-IV medical treatment of PH respective to current guidelines 18 years or older written informed consent of the patient Exclusion Criteria: pulmonary hypertension due to left ventricular dysfunction decompensated heart failure need for Catecholamines active infection pregnancy malign tumor disease other secondary disease with life expectancy < 1 year refusal by the patient

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: control<br>control group / no immunoadsorption | |
| Active Comparator: immunoadsorption<br>immunoadsorption | Procedure: immunoadsorption / immunglobulin substitution<br>* Immunoadsorption with protein-A columns on five consecutive days with subsequent human polyclonal immunoglobulin G substitution after day 5 (0,5g /kg bodyweight)<br>* Other names: immunosorba;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| pulmonary vascular Resistance | The extend of change of pulmonary vascular resistance over the observation period will be compared between the 2 groups (treatment versus control group). | 3 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| echocardiographic parameters: TAPSE | TAPSE=excursion of the lateral tricuspid annulus (measured in m-mode). the extend of cange of TAPSE over the observationperiod will be compared between the 2 groups (treatment vs. controlgroup) | 3 month | 
| NYHA | NYHA = functional capacity. The extent of change of NYHA-class over the observation period will be compared between the 2 groups (treatment versus control group). | 3 month | 
| nt pro BNP | nt pro BNP = B-type natriuretic peptide. The extent of change of nt-pro BNP over the observation period will be compared between the 2 groups (treatment versus control group). | 3 month | 
| peak oxygen uptake (spiroergometry) | The extent of change of peak oxygen uptake over the observation period will be compared between the 2 groups (treatment versus control group). | 3 month | 
| 6 min walktest | The extent of change of 6-min walktest over the observation period will be compared between the 2 groups (treatment versus control group). | 3 month | 
| ET-1 TYP A Receptor Autoantibody level | The extent of change of ET-1 TYP A Receptor Autoantibody level over the observation period will be compared between the 2 groups (treatment versus control group). | 3 month | 
| echocardiographic parameters: PAPs | PAPs = systolic pulmonalarterial pressure estimated by maximal flow velocity of tricuspid regurgitant jet (continues doppler). The extent of change of PAPs over the observation period will be compared between the 2 groups (treatment versus control group). | 3 month | 
| electrocardiographic parameters: S´lat. TR Annulus | S´lat. TR Annulus = systolic velocity of the lateral tricuspid annulus measured by tissue doppler. The extent of change of S´ lat. TR Annulus over the observation period will be compared between the 2 groups (treatment versus control group). | 3 month | 
| echocardiographic parameters: AT right ventricular outflow | AT right ventricular outflow = acceleration time of right ventricular outflow, measured by pulsed wave doppler echocardiography. The extent of change of AT over the observation period will be compared between the 2 groups (treatment versus control group). | 3 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pulmonary hypertension, autoantibodies, immunoadsorption, immunoglobulin substitution, right ventricular function