- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04797286
Sildenafil for Early Pulmonary Vascular Disease in Scleroderma (SEPVADIS)
September 12, 2023 updated by: Johns Hopkins University
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.
Study Overview
Status
Recruiting
Conditions
Intervention / Treatment
Detailed 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.
Study Type
Interventional
Enrollment (Estimated)
30
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Stephen Mathai, MD
- Phone Number: 4106146311
- Email: smathai4@jhmi.edu
Study Contact Backup
- Name: Dezeray Dutton
- Phone Number: 4435078222
- Email: dcephas1@jhu.edu
Study Locations
-
-
Louisiana
-
New Orleans, Louisiana, United States, 70806
- Not yet recruiting
- Louisiana State University
-
Principal Investigator:
- Matthew Lammi, MD
-
Contact:
- Matthew Lammi, MD
- Phone Number: 504-568-4634
-
Contact:
- Marie Sandi
- Email: mchild@lsuhsc.edu
-
-
Maryland
-
Baltimore, Maryland, United States, 21287
- Recruiting
- Johns Hopkins
-
Contact:
- Dezeray Dutton
- Phone Number: 4435078222
- Email: dcephas1@jhu.edu
-
Contact:
- Stephen Mathai, MD
- Phone Number: 410-614-6311
- Email: smathai4@jhmi.edu
-
Principal Investigator:
- Stephen Mathai, MD
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
16 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Sildenafil
Sildenafil 20 mg by mouth three(3) times each day
|
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 Names:
|
Placebo Comparator: Placebo
Placebo by mouth three(3) times each day
|
Oral pill placebo.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Difference in change in distance walked in 6 minute walk test (6MWT) at 4 months
Time Frame: Baseline and 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 Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Difference in change in distance walked in 6MWT at 12 months
Time Frame: Baseline and 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
|
Difference in change in right ventricular function as assessed by cardiac MRI
Time Frame: Baseline and 4 months
|
As assessed by change in right ventricular function (normal/abnormal) on cardiac MRI.
|
Baseline and 4 months
|
Difference in change in right ventricular function as assessed by cardiac MRI
Time Frame: Baseline and 12 months
|
As assessed by change in right ventricular function (normal/abnormal) on cardiac MRI.
|
Baseline and 12 months
|
Difference in change in right ventricular function as assessed by invasive hemodynamics
Time Frame: Baseline and 4 months
|
As assessed by change in right ventricular function (normal/abnormal) on invasive hemodynamics.
|
Baseline and 4 months
|
Difference in change in right ventricular function as assessed by invasive hemodynamics
Time Frame: Baseline and 12 months
|
As assessed by change in right ventricular function (normal/abnormal) on invasive hemodynamics.
|
Baseline and 12 months
|
Difference in change in right ventricular function as assessed by echocardiography
Time Frame: Baseline and 4 months
|
As assessed by change in right ventricular function (normal/abnormal) on echocardiography.
|
Baseline and 4 months
|
Difference in change in right ventricular function as assessed by echocardiography
Time Frame: Baseline and 12 months
|
As assessed by change in right ventricular function (normal/abnormal) on echocardiography.
|
Baseline and 12 months
|
Difference in change in N-terminal pro b-type natriuretic peptide level
Time Frame: Baseline, 4 months and 12 months
|
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
|
Difference in change in health related quality of life as assessed by the 36-Item Short Form Health Survey (SF36) questionnaire
Time Frame: Baseline, 4 months and 12 months
|
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
|
Difference in change in health related quality of life as assessed by the emPHasis-10 health-related quality of life questionnaire (emPHasis-10).
Time Frame: Baseline, 4 months and 12 months
|
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
|
Difference in safety profile as assessed by frequency of adverse events
Time Frame: Ongoing until study closes, up to 4 years
|
As assessed by frequency of adverse events between sildenafil and placebo groups.
|
Ongoing until study closes, up to 4 years
|
Difference in safety profile as assessed by severity of adverse events
Time Frame: Ongoing until study closes, up to 4 years
|
As assessed by severity of adverse events between sildenafil and placebo groups.
|
Ongoing until study closes, up to 4 years
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Stephen Mathai, MD, Johns Hopkins University
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
September 20, 2021
Primary Completion (Estimated)
September 1, 2024
Study Completion (Estimated)
September 1, 2024
Study Registration Dates
First Submitted
March 11, 2021
First Submitted That Met QC Criteria
March 11, 2021
First Posted (Actual)
March 15, 2021
Study Record Updates
Last Update Posted (Actual)
September 14, 2023
Last Update Submitted That Met QC Criteria
September 12, 2023
Last Verified
September 1, 2023
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Skin Diseases
- Connective Tissue Diseases
- Vascular Diseases
- Scleroderma, Systemic
- Scleroderma, Diffuse
- Scleroderma, Localized
- Molecular Mechanisms of Pharmacological Action
- Vasodilator Agents
- Urological Agents
- Enzyme Inhibitors
- Phosphodiesterase Inhibitors
- Phosphodiesterase 5 Inhibitors
- Sildenafil Citrate
Other Study ID Numbers
- IRB00265164
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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