VasoREACTivity Testing With Intravenous SILdenafil in Patients With Precapillary Pulmonary Hypertension

Study Overview
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Brief Summary
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Sildenafil is a selective pulmonary vasodilator; in patients with a special kind of pulmonary hypertension it is approved for treatment. The trial seeks to find out, whether the acute response to this treatment (= vasoreactivity testing) given intravenously is effective and allows prediction of therapy success during a following oral treatment.

Official Title
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Vasoreactivity Testing With Intravenous Sildenafil in Patients With Precapillary Pulmonary Hypertension (Treatment Optimisation Study)

Conditions
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Pulmonary Hypertension Associated With Connective Tissue Disease

Intervention / Treatment
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* Drug: Sildenafil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Precapillary pulmonary hypertension associated with connective tissue disease resting mean pressure in the pulmonary artery of > 24 mmHg resting mean pulmonary capillary wedge pressure (PCWP) of < 16 mmHg age 18 to 80 years women of childbearing potential must have a negative pregnancy test (ß-HCG in urine) and must use effective methods of contraception women must not be breastfeeding ability to understand and sign the informed consent, correctly signed informed consent Exclusion Criteria: pretreatment with Sildenafil contraindications for Sildenafil treatment: known intolerance to Sildenafil, optic neuropathy (NAION), known hereditary retina disease, need of nitrate therapy advanced liver cirrhosis - CHILD C severely reduced renal function with GFR < 30 ml/min/1,73 m² stroke or myocardial infarction within the last 6 months

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sildenafil<br>oral Sildenafil 20 mg three times a day for 90 days | Drug: Sildenafil<br>* oral Sildenafil 3 x 20 mg for 90 days<br>* Other names: EV Substance code SUB10517MIG;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| efficacy of Sildenafil I.V. for vasoreactivity testing | Right heart catheterisation with comprehensive hemodynamic measurements (pressures in RA, RV, PA, PCW position; cardiac index (CI) by thermodilution; oxygen saturation in the PA; the same under exercise conditions) is performed. In case of precapillary pulmonary hypertension, Sildenafil is given I.V. and acute tolerability, safety and efficacy on hemodynamic parameters are registrated. Successful vasoreactivity testing is defined by lowering the mean PA pressure by 10 mmHg or more, lowering it below 40 mmHg and maintaining / rising of the CI. Safety is mainly defined by lack of a substantial effect of the study drug on systemic blood pressure. | 1.5 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| clinical efficacy of sildenafil per os predicted by testing it intravenously in the course of oral therapy | Complete hemodynamic and functional assessment after 90 days of oral Sildenafil therapy (same protocol as before except vasoreactivity testing). Hemodynamic parameters which characterize successful oral therapy are mainly mean PA-pressure (decrease), pulmonary vascular resistance (decrease) and cardiac index (increase) - at rest and exercise. Functional improvement is further characterized by exercise capacity (cardiopulmonary exercise testing: improvement of V´O2 peak by ≥ 1 ml/min/kg), fall of NTproBNP, improvement of echocardiographic parameters of right ventricular function (TAPSE, S´, RV-FAC). Evaluation, if positive initial vasoreactivity testing results in successful oral therapy as defined above. | 90 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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vasoreactivity testing, Sildenafil, precapillary pulmonary hypertension, connective tissue disease, mean pressure in the pulmonary artery 25 mmHg or more, mean pulmonary capillary wedge pressure below 16 mmHg