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

• ClinicalTrials.gov Identifier: NCT01889966
• Recruitment Status: Completed
• First Posted: July 1, 2013
• Last Update Posted: April 28, 2015
• Sponsor: Kerckhoff Heart Center
• Collaborator: Pfizer
• Information provided by (Responsible Party): Dr. Andreas Rieth, Kerckhoff Heart Center

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Pulmonary Hypertension Associated With Connective Tissue Disease	Drug: Sildenafil	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 10 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Vasoreactivity Testing With Intravenous Sildenafil in Patients With Precapillary Pulmonary Hypertension (Treatment Optimisation Study)
• Study Start Date: April 2013
• Actual Primary Completion Date: January 2015
• Actual Study Completion Date: January 2015

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. efficacy of Sildenafil I.V. for vasoreactivity testing [ Time Frame: 1.5 hours ]
   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.

Secondary Outcome Measures :

1. clinical efficacy of sildenafil per os predicted by testing it intravenously in the course of oral therapy [ Time Frame: 90 days ]

   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.

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

Germany

Kerckhoff Heart Center

Bad Nauheim, Germany, 61231

Sponsors and Collaborators

Kerckhoff Heart Center

Pfizer

Investigators

• Principal Investigator: Andreas J Rieth, MD; Kerckhoff Heart Center

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Dr. Andreas Rieth, Dr. med., senior physician cardiology, Kerckhoff Heart Center
• ClinicalTrials.gov Identifier: NCT01889966
• Other Study ID Numbers: WS2196851
• First Posted: July 1, 2013
• Last Update Posted: April 28, 2015
• Last Verified: April 2015

Keywords provided by Dr. Andreas Rieth, Kerckhoff Heart Center:

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

Additional relevant MeSH terms:

Hypertension, Pulmonary; Hypertension; Connective Tissue Diseases; Vascular Diseases; Cardiovascular Diseases; Lung Diseases; Respiratory Tract Diseases; Sildenafil Citrate; Vasodilator Agents; Phosphodiesterase 5 Inhibitors; Phosphodiesterase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Urological Agents