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

Primary Purpose

Pulmonary Hypertension Associated With Connective Tissue Disease

Status
Completed
Phase
Phase 4
Locations
Germany
Study Type
Interventional
Intervention
Sildenafil
Sponsored by
Kerckhoff Heart Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pulmonary Hypertension Associated With Connective Tissue Disease focused on measuring 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

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Kerckhoff Heart Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Sildenafil

Arm Description

oral Sildenafil 20 mg three times a day for 90 days

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

Full Information

First Posted
June 9, 2013
Last Updated
April 26, 2015
Sponsor
Kerckhoff Heart Center
Collaborators
Pfizer
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1. Study Identification

Unique Protocol Identification Number
NCT01889966
Brief Title
VasoREACTivity Testing With Intravenous SILdenafil in Patients With Precapillary Pulmonary Hypertension
Acronym
SIL-REACT
Official Title
Vasoreactivity Testing With Intravenous Sildenafil in Patients With Precapillary Pulmonary Hypertension (Treatment Optimisation Study)
Study Type
Interventional

2. Study Status

Record Verification Date
April 2015
Overall Recruitment Status
Completed
Study Start Date
April 2013 (undefined)
Primary Completion Date
January 2015 (Actual)
Study Completion Date
January 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Kerckhoff Heart Center
Collaborators
Pfizer

4. Oversight

Data Monitoring Committee
No

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pulmonary Hypertension Associated With Connective Tissue Disease
Keywords
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Sildenafil
Arm Type
Experimental
Arm Description
oral Sildenafil 20 mg three times a day for 90 days
Intervention Type
Drug
Intervention Name(s)
Sildenafil
Other Intervention Name(s)
Revatio, CAS15 number 139755-83-2, EV Substance code SUB10517MIG
Intervention Description
oral Sildenafil 3 x 20 mg for 90 days
Primary Outcome Measure Information:
Title
efficacy of Sildenafil I.V. for vasoreactivity testing
Description
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.
Time Frame
1.5 hours
Secondary Outcome Measure Information:
Title
clinical efficacy of sildenafil per os predicted by testing it intravenously in the course of oral therapy
Description
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.
Time Frame
90 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Andreas J Rieth, MD
Organizational Affiliation
Kerckhoff Heart Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Kerckhoff Heart Center
City
Bad Nauheim
ZIP/Postal Code
61231
Country
Germany

12. IPD Sharing Statement

Citations:
PubMed Identifier
30235235
Citation
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.
Results Reference
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VasoREACTivity Testing With Intravenous SILdenafil in Patients With Precapillary Pulmonary Hypertension

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