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

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2013 by Kerckhoff Heart Center
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
Dr. Andreas Rieth, Kerckhoff Heart Center
ClinicalTrials.gov Identifier:
NCT01889966
First received: June 9, 2013
Last updated: June 26, 2013
Last verified: June 2013
  Purpose

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 Intervention Phase
Pulmonary Hypertension Associated With Connective Tissue Disease
Drug: Sildenafil
Phase 4

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Vasoreactivity Testing With Intravenous Sildenafil in Patients With Precapillary Pulmonary Hypertension (Treatment Optimisation Study)

Resource links provided by NLM:


Further study details as provided by Kerckhoff Heart Center:

Primary Outcome Measures:
  • efficacy of Sildenafil I.V. for vasoreactivity testing [ Time Frame: 1.5 hours ] [ Designated as safety issue: Yes ]
    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:
  • clinical efficacy of sildenafil per os predicted by testing it intravenously in the course of oral therapy [ Time Frame: 90 days ] [ Designated as safety issue: No ]

    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.



Estimated Enrollment: 10
Study Start Date: April 2013
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01889966

Contacts
Contact: Andreas J Rieth, MD +49 (0) 60329962677 a.rieth@kerckhoff-klinik.de
Contact: Christina Reuschling +49 (0) 60329962252 C.Reuschling@kerckhoff-forschungs-gmbh.de

Locations
Germany
Kerckhoff Heart Center Recruiting
Bad Nauheim, Germany, 61231
Contact: Andreas J Rieth, MD       a.rieth@kerckhoff-klinik.de   
Principal Investigator: Andreas J Rieth, MD         
Sub-Investigator: Veselin Mitrovic, MD Prof.         
Sponsors and Collaborators
Kerckhoff Heart Center
Pfizer
Investigators
Principal Investigator: Andreas J Rieth, MD Kerckhoff Heart Center
  More Information

No publications provided

Responsible Party: Dr. Andreas Rieth, Dr. med., senior physician cardiology, Kerckhoff Heart Center
ClinicalTrials.gov Identifier: NCT01889966     History of Changes
Other Study ID Numbers: WS2196851
Study First Received: June 9, 2013
Last Updated: June 26, 2013
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by 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:
Connective Tissue Diseases
Hypertension
Hypertension, Pulmonary
Cardiovascular Diseases
Lung Diseases
Respiratory Tract Diseases
Vascular Diseases
Sildenafil
Cardiovascular Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Phosphodiesterase 5 Inhibitors
Phosphodiesterase Inhibitors
Therapeutic Uses
Urological Agents
Vasodilator Agents

ClinicalTrials.gov processed this record on October 23, 2014