Sildenafil for Early Pulmonary Vascular Disease in Scleroderma

Scleroderma Clinical Trial

— SEPVADIS  

Official title:

Sildenafil for Early Pulmonary Vascular Disease in Scleroderma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04797286
• Other study ID #: IRB00265164
• Status: Recruiting
• Phase: Phase 2
• Start date: September 20, 2021
• Est. completion date: September 2024

Study information

• Verified date: September 2023
• Source: Johns Hopkins University
• Contact: Stephen Mathai, MD
• Phone: 4106146311
• Email: smathai4[@]jhmi.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a Phase II randomized, double-blind, placebo-controlled trial of sildenafil in men and women with Scleroderma with mildly elevated pulmonary pressures (SSc-MEP) to determine whether sildenafil may be an effective treatment for SSc-MEP.

Description:

Data shows that sildenafil (SIL) is an effective therapy in SSc-PAH. SIL has been safely used in many patients with various vascular and cardiovascular diseases over the past three decades. Randomized controlled trial data for SIL shows improvement in 6MWD, hemodynamics, and even evidence of cardiac remodeling in PAH and SSc-PAH patients. Based upon these data, SIL may be an effective therapy in SSc-MEP. This study will help determine whether sildenafil could be a good treatment for patients with scleroderma that have mildly elevated pulmonary pressures.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: September 2024
• Est. primary completion date: September 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Previous documentation of mean pulmonary artery pressure between 21 and 24 mm Hg with a pulmonary capillary wedge pressure (or left ventricular end-diastolic pressure) = 15 mm Hg within six months before study entry.
• Diagnosis of SSc according to 2013 American College of Rheumatology/ European League Against Rheumatism (ACR/EULAR) classification criteria.
• Pulmonary function tests with forced expiratory volume in one second/forced vital capacity (FEV1/FVC) >50% AND either a) total lung capacity (TLC) or forced vital capacity (FVC) > 70% predicted or b) TLC or FVC between 60% and 70% predicted with no more than mild interstitial lung disease on computerized tomography scan of the chest on studies obtained within 6 months of enrollment.
• Ventilation perfusion scan or computed tomography with intravenous contrast (CT angiogram) without evidence of chronic thromboembolism at anytime before study entry.
• Ability to perform six minute walk testing without significant limitations in musculoskeletal function or coordination.
• Informed consent.

Exclusion Criteria:

• World Health Organization (WHO) Class IV functional status.
• Systolic blood pressure less than 90 mmHg at screening visit prior to enrollment.
• Clinically significant untreated sleep apnea.
• Left-sided valvular disease (more than moderate mitral valve stenosis or insufficiency or aortic stenosis or insufficiency), pulmonary artery or valve stenosis, or ejection fraction < 45% on most recent echocardiography (within 1 year).
• Use of Pulmonary Arterial Hypertension (PAH) therapy (prostacyclin analogues, endothelin-1 receptor antagonists,phosphodiesterase-5 inhibitors, riociguat, selexipag) within the past 3 months.
• Hospitalized or acutely ill.
• Renal failure (creatinine above 2.0) at screening visit.
• Enrollment in a clinical trial or concurrent use of another investigational drug (non FDA approved) or device therapy within 30 days of screening visit.
• Age < 18.
• Currently pregnant.
• Current use of nitrates.

Related Conditions & MeSH terms

• Mildly Elevated Pulmonary Pressures
• Scleroderma
• Scleroderma, Diffuse
• Scleroderma, Localized
• Scleroderma, Systemic
• Vascular Diseases

Intervention

Drug:
• Sildenafil
Sildenafil 20 mg three times a day. This is the approved dose for the treatment of pulmonary arterial hypertension. It is being studied in this trial with a population who has mildly elevated pulmonary pressures.

Other:
• Placebo
Oral pill placebo.

Locations

Country	Name	City	State
United States	Johns Hopkins	Baltimore	Maryland
United States	Louisiana State University	New Orleans	Louisiana

Sponsors (2)

Lead Sponsor	Collaborator
Johns Hopkins University	Louisiana State University Health Sciences Center in New Orleans

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Difference in change in distance walked in 6 minute walk test (6MWT) at 4 months	As assessed by change in 6 minute walk distance (6MWD) in feet (from baseline to 4 months) between the sildenafil group and the placebo group.	Baseline and 4 months
Secondary	Difference in change in distance walked in 6MWT at 12 months	As assessed by change in 6 minute walk test distance in feet (from baseline to 12 months) between the sildenafil group and the placebo group.	Baseline and 12 months
Secondary	Difference in change in right ventricular function as assessed by cardiac MRI	As assessed by change in right ventricular function (normal/abnormal) on cardiac MRI.	Baseline and 4 months
Secondary	Difference in change in right ventricular function as assessed by cardiac MRI	As assessed by change in right ventricular function (normal/abnormal) on cardiac MRI.	Baseline and 12 months
Secondary	Difference in change in right ventricular function as assessed by invasive hemodynamics	As assessed by change in right ventricular function (normal/abnormal) on invasive hemodynamics.	Baseline and 4 months
Secondary	Difference in change in right ventricular function as assessed by invasive hemodynamics	As assessed by change in right ventricular function (normal/abnormal) on invasive hemodynamics.	Baseline and 12 months
Secondary	Difference in change in right ventricular function as assessed by echocardiography	As assessed by change in right ventricular function (normal/abnormal) on echocardiography.	Baseline and 4 months
Secondary	Difference in change in right ventricular function as assessed by echocardiography	As assessed by change in right ventricular function (normal/abnormal) on echocardiography.	Baseline and 12 months
Secondary	Difference in change in N-terminal pro b-type natriuretic peptide level	As assessed by changes in plasma N-terminal pro b-type natriuretic peptide (NT-proBNP) level (pg/mL) between sildenafil and placebo groups at four months and twelve months.	Baseline, 4 months and 12 months
Secondary	Difference in change in health related quality of life as assessed by the 36-Item Short Form Health Survey (SF36) questionnaire	As assessed by changes in SF36 questionnaire between sildenafil and placebo groups at four months and twelve months. The SF36 yields a set of scaled scores in 8 domains, with higher numbers representing a better quality of life. Each scale is scored on a 0 to 100 range so that the lowest and highest possible scores are 0 and 100, respectively. Scores represent the percentage of total possible score achieved. In step 2, items in the same scale are averaged together to create the 8 scale scores. Items that are left blank (missing data) are not taken into account when calculating the scale scores. Hence, scale scores represent the average for all items in the scale that the respondent answered.	Baseline, 4 months and 12 months
Secondary	Difference in change in health related quality of life as assessed by the emPHasis-10 health-related quality of life questionnaire (emPHasis-10).	As assessed by changes in emPHasis-10 questionnaire between sildenafil and placebo groups. The Emphasis 10 score consists of 10 questions scored in a semantic 6-point scale (from 0 to 5), for a total maximum score of 50 (the higher the score, the worse the quality of life).	Baseline, 4 months and 12 months
Secondary	Difference in safety profile as assessed by frequency of adverse events	As assessed by frequency of adverse events between sildenafil and placebo groups.	Ongoing until study closes, up to 4 years
Secondary	Difference in safety profile as assessed by severity of adverse events	As assessed by severity of adverse events between sildenafil and placebo groups.	Ongoing until study closes, up to 4 years