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RecruitingNCT04797286SEPVADISUpdated Oct 15, 2025

Sildenafil for Early Pulmonary Vascular Disease in Scleroderma

A Phase 2 interventional study of Sildenafil and Placebo in Scleroderma and Mildly Elevated Pulmonary Pressures, sponsored by Johns Hopkins University. Recruiting at 2 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-10-15.

Sponsored by Johns Hopkins University · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
30
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Scleroderma
  • Mildly Elevated Pulmonary Pressures

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Keywords

  • SSc-MEP
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

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

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.
04

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
30 participants (estimated)

Study arms

  • Experimental
    Sildenafil

    Sildenafil 20 mg by mouth three(3) times each day

    Drug: Sildenafil

  • Placebo comparator
    Placebo

    Placebo by mouth three(3) times each day

    Other: Placebo

Interventions

  • DrugSildenafil

    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.

    Also known as: Revatio, Viagra

  • OtherPlacebo

    Oral pill placebo.

05

What researchers measure

Primary outcomes

  1. 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.

    Time frame: Baseline and 4 months

Secondary outcomes

  1. 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.

    Time frame: Baseline and 12 months

  2. 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.

    Time frame: Baseline and 4 months

  3. 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.

    Time frame: Baseline and 12 months

  4. 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.

    Time frame: Baseline and 4 months

  5. 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.

    Time frame: Baseline and 12 months

  6. Difference in change in right ventricular function as assessed by echocardiography

    As assessed by change in right ventricular function (normal/abnormal) on echocardiography.

    Time frame: Baseline and 4 months

  7. Difference in change in right ventricular function as assessed by echocardiography

    As assessed by change in right ventricular function (normal/abnormal) on echocardiography.

    Time frame: Baseline and 12 months

  8. 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.

    Time frame: Baseline, 4 months and 12 months

  9. 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.

    Time frame: Baseline, 4 months and 12 months

  10. 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).

    Time frame: Baseline, 4 months and 12 months

  11. Difference in safety profile as assessed by frequency of adverse events

    As assessed by frequency of adverse events between sildenafil and placebo groups.

    Time frame: Ongoing until study closes, up to 4 years

  12. Difference in safety profile as assessed by severity of adverse events

    As assessed by severity of adverse events between sildenafil and placebo groups.

    Time frame: Ongoing until study closes, up to 4 years

06

Study locations

1 of 2 sites recruiting
  • Louisiana State University
    New Orleans, Louisiana 70806, United States
    • Matthew Lammi, MD · Contact · 504-568-4634
    • Marie Sandi · Contact · mchild@lsuhsc.edu
    • Matthew Lammi, MD · Principal investigator
    Not yet recruiting
  • Johns Hopkins
    Baltimore, Maryland 21287, United States
    • Stephen Mathai, MD · Contact · smathai4@jhmi.edu · 410-614-6311
    • Dezeray Dutton · Contact · dcephas1@jhu.edu · 4435078222
    • Stephen Mathai, MD · Principal investigator
    Recruiting
07

References and documents

Publications

  • Lammi MR, Mukherjee M, Saketkoo LA, Carey K, Hummers L, Hsu S, Krishnan A, Sandi M, Shah AA, Zimmerman SL, Hassoun PM, Mathai SC. Sildenafil Versus Placebo for Early Pulmonary Vascular Disease in Scleroderma (SEPVADIS): protocol for a randomized controlled trial. BMC Pulm Med. 2024 Apr 30;24(1):211. doi: 10.1186/s12890-024-02892-3. PubMed 38689245 ↗

Individual participant data

Plan to share: No

08

Registry details

Key details

Study ID
NCT04797286
Lead sponsor
Johns Hopkins University
Collaborators
Louisiana State University Health Sciences Center in New Orleans, United States Department of Defense
Responsible party
Sponsor
First posted
Mar 15, 2021
Start date
Sep 20, 2021
Primary completion
Sep 1, 2026 (estimated)
Completion
Sep 1, 2026 (estimated)
Last update
Oct 15, 2025

Study contacts

Stephen Mathai, MD
Contact
smathai4@jhmi.edu
4106146311
Renee Ofori
Contact
rofori2@jhu.edu
410-614-6311
Stephen Mathai, MD
principal investigator · Johns Hopkins University

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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