VasoREACTivity Testing With Intravenous SILdenafil in Patients With Precapillary Pulmonary Hypertension (SIL-REACT)

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

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.

Study Overview

• Status: Completed
• Conditions: Pulmonary Hypertension Associated With Connective Tissue Disease
• Intervention / Treatment: Drug: Sildenafil

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 4

Contacts and Locations

Study Locations

• Germany
  • Bad Nauheim, Germany, 61231
    • Kerckhoff Heart Center

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:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Sildenafil; oral Sildenafil 20 mg three times a day for 90 days	Drug: Sildenafil; oral Sildenafil 3 x 20 mg for 90 days; Other Names: Revatio; CAS15 number 139755-83-2; EV Substance code SUB10517MIG

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Kerckhoff Heart Center
• Collaborators: Pfizer
• Investigators: Principal Investigator: Andreas J Rieth, MD, Kerckhoff Heart Center

Publications and helpful links

General Publications

• Rieth AJ, Richter MJ, Berkowitsch A, Frerix M, Tarner IH, Mitrovic V, Hamm CW. Intravenous sildenafil acutely improves hemodynamic response to exercise in patients with connective tissue disease. PLoS One. 2018 Sep 20;13(9):e0203947. doi: 10.1371/journal.pone.0203947. eCollection 2018.

Study record dates

Study Major Dates

• Study Start: April 1, 2013
• Primary Completion (ACTUAL): January 1, 2015
• Study Completion (ACTUAL): January 1, 2015

Study Registration Dates

• First Submitted: June 9, 2013
• First Submitted That Met QC Criteria: June 26, 2013
• First Posted (ESTIMATE): July 1, 2013

Study Record Updates

• Last Update Posted (ESTIMATE): April 28, 2015
• Last Update Submitted That Met QC Criteria: April 26, 2015
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Keywords: Sildenafil; connective tissue disease; vasoreactivity testing; precapillary pulmonary hypertension; mean pressure in the pulmonary artery 25 mmHg or more; mean pulmonary capillary wedge pressure below 16 mmHg
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension; Hypertension, Pulmonary; Connective Tissue Diseases; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Urological Agents; Enzyme Inhibitors; Phosphodiesterase Inhibitors; Phosphodiesterase 5 Inhibitors; Sildenafil Citrate
• Other Study ID Numbers: WS2196851